Author: "Greene M.H." - Searchworks@Jio Institute Digital Library Search Results

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155 results on '"Greene M.H."'

1. Genome-wide Association Study of Bladder Cancer Reveals New Biological and Translational Insights.

Author: Koutros, S., Kiemeney, L.A., Pal Choudhury, P., Milne, R.L., Lopez de Maturana, E., Ye, Y., Joseph, V., Florez-Vargas, O., Dyrskjøt, L., Figueroa, J., Dutta, D., Giles, G.G., Hildebrandt, M.A.T., Offit, K., Kogevinas, M., Weiderpass, E., McCullough, M.L., Freedman, N.D., Albanes, D., Kooperberg, C., Cortessis, V.K., Karagas, M.R., Johnson, A., Schwenn, M.R., Baris, D., Furberg, H., Bajorin, D.F., Cussenot, O., Cancel-Tassin, G., Benhamou, S., Kraft, P., Porru, S., Carta, A., Bishop, T., Southey, M.C., Matullo, G., Fletcher, T., Kumar, R., Taylor, J.A., Lamy, P., Prip, F., Kalisz, M., Weinstein, S.J., Hengstler, J.G., Selinski, S., Harland, M., Teo, M., Kiltie, A.E., Tardón, A., Serra, C., Carrato, A., García-Closas, R., Lloreta, J., Schned, A., Lenz, P., Riboli, E., Brennan, P., Tjønneland, A., Otto, T., Ovsiannikov, D., Volkert, F., Vermeulen, S.H., Aben, K.K.H., Galesloot, T.E., Turman, C., Vivo, I. De, Giovannucci, E., Hunter, D.J., Hohensee, C., Hunt, R., Patel, A.V., Huang, W.Y., Thorleifsson, G., Gago-Dominguez, M., Amiano, P., Golka, K., Stern, M.C., Yan, W., Liu, J., Li, S.A., Katta, S., Hutchinson, A., Hicks, B., Wheeler, W.A., Purdue, M.P., McGlynn, K.A., Kitahara, C.M., Haiman, C.A., Greene, M.H., Rafnar, T., Chatterjee, N., Chanock, S.J., Wu, X., Real, F.X., Silverman, D.T., Garcia-Closas, M., Stefansson, K., Prokunina-Olsson, L., Malats, N., Rothman, N., Koutros, S., Kiemeney, L.A., Pal Choudhury, P., Milne, R.L., Lopez de Maturana, E., Ye, Y., Joseph, V., Florez-Vargas, O., Dyrskjøt, L., Figueroa, J., Dutta, D., Giles, G.G., Hildebrandt, M.A.T., Offit, K., Kogevinas, M., Weiderpass, E., McCullough, M.L., Freedman, N.D., Albanes, D., Kooperberg, C., Cortessis, V.K., Karagas, M.R., Johnson, A., Schwenn, M.R., Baris, D., Furberg, H., Bajorin, D.F., Cussenot, O., Cancel-Tassin, G., Benhamou, S., Kraft, P., Porru, S., Carta, A., Bishop, T., Southey, M.C., Matullo, G., Fletcher, T., Kumar, R., Taylor, J.A., Lamy, P., Prip, F., Kalisz, M., Weinstein, S.J., Hengstler, J.G., Selinski, S., Harland, M., Teo, M., Kiltie, A.E., Tardón, A., Serra, C., Carrato, A., García-Closas, R., Lloreta, J., Schned, A., Lenz, P., Riboli, E., Brennan, P., Tjønneland, A., Otto, T., Ovsiannikov, D., Volkert, F., Vermeulen, S.H., Aben, K.K.H., Galesloot, T.E., Turman, C., Vivo, I. De, Giovannucci, E., Hunter, D.J., Hohensee, C., Hunt, R., Patel, A.V., Huang, W.Y., Thorleifsson, G., Gago-Dominguez, M., Amiano, P., Golka, K., Stern, M.C., Yan, W., Liu, J., Li, S.A., Katta, S., Hutchinson, A., Hicks, B., Wheeler, W.A., Purdue, M.P., McGlynn, K.A., Kitahara, C.M., Haiman, C.A., Greene, M.H., Rafnar, T., Chatterjee, N., Chanock, S.J., Wu, X., Real, F.X., Silverman, D.T., Garcia-Closas, M., Stefansson, K., Prokunina-Olsson, L., Malats, N., and Rothman, N.
Abstract: 01 juli 2023, Item does not contain fulltext, BACKGROUND: Genomic regions identified by genome-wide association studies (GWAS) for bladder cancer risk provide new insights into etiology. OBJECTIVE: To identify new susceptibility variants for bladder cancer in a meta-analysis of new and existing genome-wide genotype data. DESIGN, SETTING, AND PARTICIPANTS: Data from 32 studies that includes 13,790 bladder cancer cases and 343,502 controls of European ancestry were used for meta-analysis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: Log-additive associations of genetic variants were assessed using logistic regression models. A fixed-effects model was used for meta-analysis of the results. Stratified analyses were conducted to evaluate effect modification by sex and smoking status. A polygenic risk score (PRS) was generated on the basis of known and novel susceptibility variants and tested for interaction with smoking. RESULTS AND LIMITATIONS: Multiple novel bladder cancer susceptibility loci (6p.22.3, 7q36.3, 8q21.13, 9p21.3, 10q22.1, 19q13.33) as well as improved signals in three known regions (4p16.3, 5p15.33, 11p15.5) were identified, bringing the number of independent markers at genome-wide significance (p < 5 × 10(-8)) to 24. The 4p16.3 (FGFR3/TACC3) locus was associated with a stronger risk for women than for men (p-interaction = 0.002). Bladder cancer risk was increased by interactions between smoking status and genetic variants at 8p22 (NAT2; multiplicative p value for interaction [p(M-I)] = 0.004), 8q21.13 (PAG1; p(M-I) = 0.01), and 9p21.3 (LOC107987026/MTAP/CDKN2A; p(M-I) = 0.02). The PRS based on the 24 independent GWAS markers (odds ratio per standard deviation increase 1.49, 95% confidence interval 1.44-1.53), which also showed comparable results in two prospective cohorts (UK Biobank, PLCO trial), revealed an approximately fourfold difference in the lifetime risk of bladder cancer according to the PRS (e.g., 1st vs 10th decile) for both smokers and nonsmokers. CONCLUSIONS: We report novel loci ass
Published: 2023

2. Polygenic risk modeling for prediction of epithelial ovarian cancer risk

Author: Dareng, E.O., Tyrer, J.P., Barnes, D.R., Jones, M.R., Yang, X, Aben, K.K.H., Adank, M.A., Agata, S., Andrulis, I.L., Anton-Culver, H., Antonenkova, N.N., Aravantinos, G., Arun, B.K., Augustinsson, A., Balmaña, J., Bandera, E.V., Barkardottir, R.B., Barrowdale, D., Beckmann, M.W., Beeghly-Fadiel, A., Benitez, J., Bermisheva, M., Bernardini, M.Q., Bjorge, L., Black, A., Bogdanova, N.V., Bonanni, B., Borg, A., Brenton, J.D., Budzilowska, A., Butzow, R., Buys, S.S., Cai, H., Caligo, M.A., Campbell, I., Cannioto, R., Cassingham, H., Chang-Claude, J., Chanock, S.J., Chen, K., Chiew, Y.E., Chung, W.K., Claes, K.B.M., Colonna, S., Cook, L.S., Couch, F.J., Daly, M.B., Dao, F., Davies, E., Hoya, M. de la, Putter, R. de, Dennis, J., DePersia, A., Devilee, P., Diez, O., Ding, Y.C., Doherty, J.A., Domchek, S.M., Dörk, T., Bois, A. du, Dürst, M., Eccles, D.M., Eliassen, H.A., Engel, C., Evans, G.D., Fasching, P.A., Flanagan, J.M., Fortner, R.T., Machackova, E., Friedman, E., Ganz, P.A., Garber, J., Gensini, F., Giles, G.G., Glendon, G., Godwin, A.K., Goodman, M.T., Greene, M.H., Gronwald, J., Hahnen, E., Haiman, C.A., Håkansson, N., Hamann, U., Hansen, T.V., Harris, H.R., Hartman, M, Heitz, F., Hildebrandt, M.A., Høgdall, E., Høgdall, C.K., Hopper, J.L., Huang, R.Y., Huff, C., Hulick, P.J., Huntsman, D.G., Imyanitov, E.N., Isaacs, C., Jakubowska, A., James, P.A., Kiemeney, L.A.L.M., Altena, A.M. van, Janavicius, R., Antoniou, A.C., Pharoah, P.D., Dareng, E.O., Tyrer, J.P., Barnes, D.R., Jones, M.R., Yang, X, Aben, K.K.H., Adank, M.A., Agata, S., Andrulis, I.L., Anton-Culver, H., Antonenkova, N.N., Aravantinos, G., Arun, B.K., Augustinsson, A., Balmaña, J., Bandera, E.V., Barkardottir, R.B., Barrowdale, D., Beckmann, M.W., Beeghly-Fadiel, A., Benitez, J., Bermisheva, M., Bernardini, M.Q., Bjorge, L., Black, A., Bogdanova, N.V., Bonanni, B., Borg, A., Brenton, J.D., Budzilowska, A., Butzow, R., Buys, S.S., Cai, H., Caligo, M.A., Campbell, I., Cannioto, R., Cassingham, H., Chang-Claude, J., Chanock, S.J., Chen, K., Chiew, Y.E., Chung, W.K., Claes, K.B.M., Colonna, S., Cook, L.S., Couch, F.J., Daly, M.B., Dao, F., Davies, E., Hoya, M. de la, Putter, R. de, Dennis, J., DePersia, A., Devilee, P., Diez, O., Ding, Y.C., Doherty, J.A., Domchek, S.M., Dörk, T., Bois, A. du, Dürst, M., Eccles, D.M., Eliassen, H.A., Engel, C., Evans, G.D., Fasching, P.A., Flanagan, J.M., Fortner, R.T., Machackova, E., Friedman, E., Ganz, P.A., Garber, J., Gensini, F., Giles, G.G., Glendon, G., Godwin, A.K., Goodman, M.T., Greene, M.H., Gronwald, J., Hahnen, E., Haiman, C.A., Håkansson, N., Hamann, U., Hansen, T.V., Harris, H.R., Hartman, M, Heitz, F., Hildebrandt, M.A., Høgdall, E., Høgdall, C.K., Hopper, J.L., Huang, R.Y., Huff, C., Hulick, P.J., Huntsman, D.G., Imyanitov, E.N., Isaacs, C., Jakubowska, A., James, P.A., Kiemeney, L.A.L.M., Altena, A.M. van, Janavicius, R., Antoniou, A.C., and Pharoah, P.D.
Abstract: Item does not contain fulltext, Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, "select and shrink for summary statistics" (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28-1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08-1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21-1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29-1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35-1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.
Published: 2022

3. Association Study between Polymorphisms in DNA Methylation-Related Genes and Testicular Germ Cell Tumor Risk

Author: Grasso, C., Popovic, M., Isaevska, E., Lazzarato, F., Fiano, V., Zugna, D., Pluta, J., Weathers, B., D'Andrea, K., Almstrup, K., Anson-Cartwright, L., Bishop, D.T., Chanock, S.J., Chen, C, Cortessis, V.K., Dalgaard, M.D., Daneshmand, S., Ferlin, A., Foresta, C., Frone, M.N., Gamulin, M., Gietema, J.A., Greene, M.H., Grotmol, T., Hamilton, R.J., Haugen, T.B., Hauser, R., Karlsson, R., Kiemeney, L.A.L.M., Lessel, D., Lista, P., Lothe, R.A., Loveday, C., Meijer, C., Nead, K.T., Nsengimana, J., Skotheim, R.I., Turnbull, C., Vaughn, D.J., Wiklund, F., Zheng, T., Zitella, A., Schwartz, S.M., McGlynn, K.A., Kanetsky, P.A., Nathanson, K.L., Richiardi, L., Grasso, C., Popovic, M., Isaevska, E., Lazzarato, F., Fiano, V., Zugna, D., Pluta, J., Weathers, B., D'Andrea, K., Almstrup, K., Anson-Cartwright, L., Bishop, D.T., Chanock, S.J., Chen, C, Cortessis, V.K., Dalgaard, M.D., Daneshmand, S., Ferlin, A., Foresta, C., Frone, M.N., Gamulin, M., Gietema, J.A., Greene, M.H., Grotmol, T., Hamilton, R.J., Haugen, T.B., Hauser, R., Karlsson, R., Kiemeney, L.A.L.M., Lessel, D., Lista, P., Lothe, R.A., Loveday, C., Meijer, C., Nead, K.T., Nsengimana, J., Skotheim, R.I., Turnbull, C., Vaughn, D.J., Wiklund, F., Zheng, T., Zitella, A., Schwartz, S.M., McGlynn, K.A., Kanetsky, P.A., Nathanson, K.L., and Richiardi, L.
Abstract: Item does not contain fulltext, BACKGROUND: Testicular germ cell tumors (TGCT), histologically classified as seminomas and nonseminomas, are believed to arise from primordial gonocytes, with the maturation process blocked when they are subjected to DNA methylation reprogramming. SNPs in DNA methylation machinery and folate-dependent one-carbon metabolism genes have been postulated to influence the proper establishment of DNA methylation. METHODS: In this pathway-focused investigation, we evaluated the association between 273 selected tag SNPs from 28 DNA methylation-related genes and TGCT risk. We carried out association analysis at individual SNP and gene-based level using summary statistics from the Genome Wide Association Study meta-analysis recently conducted by the international Testicular Cancer Consortium on 10,156 TGCT cases and 179,683 controls. RESULTS: In individual SNP analyses, seven SNPs, four mapping within MTHFR, were associated with TGCT risk after correction for multiple testing (q ≤ 0.05). Queries of public databases showed that three of these SNPs were associated with MTHFR changes in enzymatic activity (rs1801133) or expression level in testis tissue (rs12121543, rs1476413). Gene-based analyses revealed MTHFR (q = 8.4 × 10-4), methyl-CpG-binding protein 2 (MECP2; q = 2 × 10-3), and ZBTB4 (q = 0.03) as the top TGCT-associated genes. Stratifying by tumor histology, four MTHFR SNPs were associated with seminoma. In gene-based analysis MTHFR was associated with risk of seminoma (q = 2.8 × 10-4), but not with nonseminomatous tumors (q = 0.22). CONCLUSIONS: Genetic variants within MTHFR, potentially having an impact on the DNA methylation pattern, are associated with TGCT risk. IMPACT: This finding suggests that TGCT pathogenesis could be associated with the folate cycle status, and this relation could be partly due to hereditary factors.
Published: 2022

4. Prevalence of Family History of Breast, Colorectal, Prostate, and Lung Cancer in a Population-Based Study

Author: Mai, P.L., Wideroff, L., Greene, M.H., and Graubard, B.I.
Published: 2010

5. Height and Body Mass Index as Modifiers of Breast Cancer Risk in BRCA1/2 Mutation Carriers: A Mendelian Randomization Study

Author: Qian, F., Wang, S.F., Mitchell, J., McGuffog, L., Barrowdale, D., Leslie, G., Oosterwijk, J.C., Chung, W.K., Evans, D.G., Engel, C., Kast, K., Aalfs, C.M., Adank, M.A., Adlard, J., Agnarsson, B.A., Aittomaki, K., Alducci, E., Andrulis, I.L., Arun, B.K., Ausems, M.G.E.M., Azzollini, J., Barouk-Simonet, E., Barwell, J., Belotti, M., Benitez, J., Berger, A., Borg, A., Bradbury, A.R., Brunet, J., Buys, S.S., Caldes, T., Caligo, M.A., Campbell, I., Caputo, S.M., Chiquette, J., Claes, K.B.M., Collee, J.M., Couch, F.J., Coupier, I., Daly, M.B., Davidson, R., Diez, O., Domchek, S.M., Donaldson, A., Dorfling, C.M., Eeles, R., Feliubadalo, L., Foretova, L., Fowler, J., Friedman, E., Frost, D., Ganz, P.A., Garber, J., Garcia-Barberan, V., Glendon, G., Godwin, A.K., Garcia, E.B.G., Gronwald, J., Hahnen, E., Hamann, U., Henderson, A., Hendricks, C.B., Hopper, J.L., Hulick, P.J., Imyanitov, E.N., Isaacs, C., Izatt, L., Izquierdo, A., Jakubowska, A., Kaczmarek, K., Kang, E., Karlan, B.Y., Kets, C.M., Kim, S.W., Kim, Z., Kwong, A., Laitman, Y., Lasset, C., Lee, M.H., Lee, J.W., Lee, J., Lester, J., Lesueur, F., Loud, J.T., Lubinski, J., Mebirouk, N., Meijers-Heijboer, H.E.J., Meindl, A., Miller, A., Montagna, M., Mooij, T.M., Morrison, P.J., Mouret-Fourme, E., Nathanson, K.L., Neuhausen, S.L., Nevanlinna, H., Niederacher, D., Nielsen, F.C., Nussbaum, R.L., Offit, K., Olah, E., Ong, K.R., Ottini, L., Park, S.K., Peterlongo, P., Pfeiler, G., Phelan, C.M., Poppe, B., Pradhan, N., Radice, P., Ramus, S.J., Rantala, J., Robson, M., Rodriguez, G.C., Schmutzler, R.K., Selkirk, C.G.H., Shah, P.D., Simard, J., Singer, C.F., Sokolowska, J., Stoppa-Lyonnet, D., Sutter, C., Tan, Y.Y., Teixeira, M.R., Teo, S.H., Terry, M.B., Thomassen, M., Tischkowitz, M., Toland, A.E., Tucker, K.M., Tung, N., Asperen, C.J. van, Engelen, K. van, Rensburg, E.J. van, Wang-Gohrke, S., Wappenschmidt, B., Weitzel, J.N., Yannoukakos, D., Greene, M.H., Rookus, M.A., Easton, D.F., Chenevix-Trench, G., Antoniou, A.C., Goldgar, D.E., Olopade, O.I., Rebbeck, T.R., Huo, D.Z., GEMO Study Collaborators, HEBON, EMBRACE, Clinical Genetics, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Targeted Gynaecologic Oncology (TARGON), Leslie, Goska [0000-0001-5756-6222], Tischkowitz, Marc [0000-0002-7880-0628], Easton, Douglas [0000-0003-2444-3247], Antoniou, Antonis [0000-0001-9223-3116], Apollo - University of Cambridge Repository, Klinische Genetica, MUMC+: DA KG Polikliniek (9), RS: GROW - R4 - Reproductive and Perinatal Medicine, Human Genetics, ARD - Amsterdam Reproduction and Development, Epidemiology and Data Science, Human genetics, CCA - Cancer biology and immunology, Amsterdam Neuroscience - Complex Trait Genetics, and Amsterdam Reproduction & Development (AR&D)
Subjects: Oncology, Cancer Research, LOCI, Disease, DISEASE, Body Mass Index, breast cancer risk, 0302 clinical medicine, Risk Factors, GENETIC-VARIANTS, EPIDEMIOLOGY, skin and connective tissue diseases, 2. Zero hunger, BRCA1 Protein, Articles, Prognosis, INSULIN, 3. Good health, Women's cancers Radboud Institute for Health Sciences [Radboudumc 17], FAMILY, 030220 oncology & carcinogenesis, OBESITY, BIOLOGICAL PATHWAYS, Female, Risk assessment, Adult, medicine.medical_specialty, Breast Neoplasms, Polymorphism, Single Nucleotide, EMBRACE, GEMO Study Collaborators, BMI, 03 medical and health sciences, Breast cancer, SDG 3 - Good Health and Well-being, BRCA1/2, Internal medicine, Mendelian randomization, medicine, Journal Article, Humans, Genetic Predisposition to Disease, HEBON, BRCA2 Protein, IDENTIFICATION, Proportional hazards model, business.industry, Mendelian Randomization Analysis, medicine.disease, Obesity, Confidence interval, Body Height, Mutation, WEIGHT, business, Body mass index
Abstract: Contains fulltext : 206539.pdf (Publisher’s version ) (Closed access) BACKGROUND: BRCA1/2 mutations confer high lifetime risk of breast cancer, although other factors may modify this risk. Whether height or body mass index (BMI) modifies breast cancer risk in BRCA1/2 mutation carriers remains unclear. METHODS: We used Mendelian randomization approaches to evaluate the association of height and BMI on breast cancer risk, using data from the Consortium of Investigators of Modifiers of BRCA1/2 with 14 676 BRCA1 and 7912 BRCA2 mutation carriers, including 11 451 cases of breast cancer. We created a height genetic score using 586 height-associated variants and a BMI genetic score using 93 BMI-associated variants. We examined both observed and genetically determined height and BMI with breast cancer risk using weighted Cox models. All statistical tests were two-sided. RESULTS: Observed height was positively associated with breast cancer risk (HR = 1.09 per 10 cm increase, 95% confidence interval [CI] = 1.0 to 1.17; P = 1.17). Height genetic score was positively associated with breast cancer, although this was not statistically significant (per 10 cm increase in genetically predicted height, HR = 1.04, 95% CI = 0.93 to 1.17; P = .47). Observed BMI was inversely associated with breast cancer risk (per 5 kg/m2 increase, HR = 0.94, 95% CI = 0.90 to 0.98; P = .007). BMI genetic score was also inversely associated with breast cancer risk (per 5 kg/m2 increase in genetically predicted BMI, HR = 0.87, 95% CI = 0.76 to 0.98; P = .02). BMI was primarily associated with premenopausal breast cancer. CONCLUSION: Height is associated with overall breast cancer and BMI is associated with premenopausal breast cancer in BRCA1/2 mutation carriers. Incorporating height and BMI, particularly genetic score, into risk assessment may improve cancer management.
Published: 2019

6. A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Author: Coignard, J., Lush, M., Beesley, J., O'Mara, T.A., Dennis, J., Tyrer, J.P., Barnes, D.R., McGuffog, L., Leslie, G., Bolla, M.K., Adank, M.A., Agata, S., Ahearn, T., Aittomäki, K., Andrulis, I.L., Anton-Culver, H., Arndt, V., Arnold, N., Aronson, K.J., Arun, B.K., Augustinsson, A., Azzollini, J., Barrowdale, D., Baynes, C., Becher, H., Bermisheva, M., Bernstein, L., Białkowska, K., Blomqvist, C., Bojesen, S.E., Bonanni, B., Borg, A., Brauch, H., Brenner, H., Burwinkel, B., Buys, S.S., Caldés, T., Caligo, M.A., Campa, D., Carter, B.D., Castelao, J.E., Chang-Claude, J., Chanock, S.J., Chung, W.K., Claes, K.B.M., Clarke, C.L., Collée, J.M., Conroy, D.M., Czene, K., Daly, M.B., Devilee, P., Diez, O., Ding, Y.C., Domchek, S.M., Dörk, T., Dos-Santos-Silva, I., Dunning, A.M., Dwek, M., Eccles, D.M., Eliassen, A.H., Engel, C., Eriksson, M., Evans, D.G., Fasching, P.A., Flyger, H., Fostira, F., Friedman, E., Fritschi, L., Frost, D., Gago-Dominguez, M., Gapstur, S.M., Garber, J., Garcia-Barberan, V., García-Closas, M., García-Sáenz, J.A., Gaudet, M.M., Gayther, S.A., Gehrig, A., Georgoulias, V., Giles, G.G., Godwin, A.K., Goldberg, M.S., Goldgar, D.E., González-Neira, A., Greene, M.H., Guénel, P., Haeberle, L., Hahnen, E., Haiman, C.A., Håkansson, N., Hall, P., Hamann, U., Harrington, Patrick, Hart, S.N., He, W., Hogervorst, F.B., Hollestelle, A., Mensenkamp, A.R., Hopper, J.L., Horcasitas, D.J., Hulick, P.J., Coignard, J., Lush, M., Beesley, J., O'Mara, T.A., Dennis, J., Tyrer, J.P., Barnes, D.R., McGuffog, L., Leslie, G., Bolla, M.K., Adank, M.A., Agata, S., Ahearn, T., Aittomäki, K., Andrulis, I.L., Anton-Culver, H., Arndt, V., Arnold, N., Aronson, K.J., Arun, B.K., Augustinsson, A., Azzollini, J., Barrowdale, D., Baynes, C., Becher, H., Bermisheva, M., Bernstein, L., Białkowska, K., Blomqvist, C., Bojesen, S.E., Bonanni, B., Borg, A., Brauch, H., Brenner, H., Burwinkel, B., Buys, S.S., Caldés, T., Caligo, M.A., Campa, D., Carter, B.D., Castelao, J.E., Chang-Claude, J., Chanock, S.J., Chung, W.K., Claes, K.B.M., Clarke, C.L., Collée, J.M., Conroy, D.M., Czene, K., Daly, M.B., Devilee, P., Diez, O., Ding, Y.C., Domchek, S.M., Dörk, T., Dos-Santos-Silva, I., Dunning, A.M., Dwek, M., Eccles, D.M., Eliassen, A.H., Engel, C., Eriksson, M., Evans, D.G., Fasching, P.A., Flyger, H., Fostira, F., Friedman, E., Fritschi, L., Frost, D., Gago-Dominguez, M., Gapstur, S.M., Garber, J., Garcia-Barberan, V., García-Closas, M., García-Sáenz, J.A., Gaudet, M.M., Gayther, S.A., Gehrig, A., Georgoulias, V., Giles, G.G., Godwin, A.K., Goldberg, M.S., Goldgar, D.E., González-Neira, A., Greene, M.H., Guénel, P., Haeberle, L., Hahnen, E., Haiman, C.A., Håkansson, N., Hall, P., Hamann, U., Harrington, Patrick, Hart, S.N., He, W., Hogervorst, F.B., Hollestelle, A., Mensenkamp, A.R., Hopper, J.L., Horcasitas, D.J., and Hulick, P.J.
Abstract: Contains fulltext : 231768.pdf (publisher's version ) (Open Access), Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10(-8), at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers.
Published: 2021

7. A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Author: Coignard, J. (Juliette), Lush, M. (Michael), Beesley, J. (Jonathan), O’Mara, T.A. (Tracy A.), Dennis, J. (Joe), Tyrer, J.P. (Jonathan P.), Barnes, D. (Daniel), McGuffog, L. (Lesley), Leslie, G. (Goska), Bolla, M.K. (Manjeet K.), Adank, M.A. (Muriel), Agata, S. (Simona), Ahearn, T. (Thomas), Aittomäki, K. (Kristiina), Andrulis, I.L. (Irene L.), Anton-Culver, H. (Hoda), Arndt, V. (Volker), Arnold, N. (Norbert), Aronson, K.J. (Kristan J.), Arun, B.K. (Banu), Augustinsson, A. (Annelie), Azzollini, J., Barrowdale, D. (Daniel), Baynes, C. (Caroline), Becher, H. (Heko), Bermisheva, M. (Marina), Bernstein, L. (Leslie), Białkowska, K. (Katarzyna), Blomqvist, C. (Carl), Bojesen, S.E. (Stig), Bonnani, B. (Bernardo), Borg, Å. (Åke), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Burwinkel, B. (Barbara), Buys, S.S. (Saundra S.), Caldes, T. (Trinidad), Caligo, M.A. (Maria A.), Campa, D. (Daniele), Carter, B.D. (Brian D.), Castelao, J.E. (Jose ), Chang-Claude, J. (Jenny), Chanock, S.J. (Stephen J.), Chung, W.K. (Wendy K.), Claes, K.B.M. (Kathleen B. M.), Clarke, C.L. (Christine L.), Bertrand, O. (Ophélie), Caputo, S. (Sandrine), Dupré, A. (Anaïs), Le Mentec, M. (Marine), Belotti, M. (Muriel), Birot, A.-M. (Anne-Marie), Buecher, B. (Bruno), Fourme, E. (Emmanuelle), Gauthier-Villars, M. (Marion), Golmard, L. (Lisa), Houdayer, C. (Claude), Moncoutier, V. (Virginie), de Pauw, A. (Antoine), Saule, C. (Claire), Sinilnikova, O. (Olga), Mazoyer, S. (Sylvie), Damiola, F. (Francesca), Barjhoux, L. (Laure), Verny-Pierre, C. (Carole), Léone, M. (Mélanie), Boutry-Kryza, N. (N.), Calender, A. (Alain), Giraud, S. (Sophie), Caron, O. (Olivier), Guillaud-Bataille, M. (Marine), Bressac-de Paillerets, B. (Brigitte), Bignon, Y.-J. (Yves-Jean), Uhrhammer, N. (Nancy), Lasset, C. (Christine), Bonadona, V. (Valérie), Berthet, P. (Pascaline), Vaur, D. (Dominique), Castera, L. (Laurent), Noguchi, T. (Tetsuro), Popovici, C. (Cornel), Sobol, H. (Hagay), Bourdon, V. (Violaine), Remenieras, A. (Audrey), Nogues, C. (Catherine), Coupier, I. (Isabelle), Pujol, P. (Pascal), Dumont, A. (Aurélie), Révillion, F. (Françoise), Adenis, C. (Claude), Muller, D.W. (Danièle), Barouk-Simonet, E. (Emmanuelle), Bonnet, F. (Françoise), Bubien, V. (Virginie), Sevenet, N. (Nicolas), Longy, M. (Michel), Toulas, C. (Christine), Guimbaud, R. (Rosine), Gladieff, L. (Laurence), Feillel, V. (Viviane), Leroux, D. (Dominique), Dreyfus, H. (Hélène), Rebischung, C. (Christine), Peysselon, M. (Magalie), Coron, F. (Fanny), Faivre, L. (Laurence), Baurand, A. (Amandine), Jacquot, C. (Caroline), Bertolone, G. (Geoffrey), Lizard, S. (Sarab), Prieur, F. (Fabienne), Lebrun, M. (Marine), Kientz, C. (Caroline), Ferrer, S.F., Mari, V. (Véronique), Vénat-Bouvet, L. (Laurence), Delnatte, C. (Capucine), Bézieau, S. (Stéphane), Mortemousque, I. (Isabelle), Coulet, F. (Florence), Colas, C. (Chrystelle), Soubrier, F. (Florent), Warcoin, M. (Mathilde), Sokolowska, J. (Johanna), Bronner, M. (Myriam), Collonge-Rame, M.-A., Damette, A. (Alexandre), Gesta, P. (Paul), Lallaoui, H. (Hakima), Chiesa, J. (Jean), Molina-Gomes, D. (Denise), Ingster, O. (Olivier), Gregory, H. (Helen), Miedzybrodzka, Z. (Zosia), Morrison, P.J. (Patrick J.), Ong, K.-R. (Kai-ren), Donaldson, A. (Alan), Rogers, M.T. (Mark), Kennedy, M.J. (M. John), Porteous, M.E. (Mary), Brewer, C. (Carole), Davidson, R. (Rosemarie), Izatt, L. (Louise), Brady, A. (A.), Barwell, J. (Julian), Adlard, J.W. (Julian), Foo, C. (Claire), Lalloo, F. (Fiona), Side, L.E. (Lucy E.), Eason, J. (Jacqueline), Henderson, A. (Alex), Walker, L. (Lisa), Eeles, R. (Rosalind), Cook, J. (Jackie), Snape, K. (Katie), Eccles, D. (Diana), Murray, A. (Alexandra), McCann, E. (Emma), Collée, J.M. (J. Margriet), Conroy, D.M. (Don M.), Czene, K. (Kamila), Daly, M.B. (Mary B.), Devilee, P. (Peter), Diez, O. (Orland), Ding, Y.C. (Yuan Chun), Domchek, S.M. (Susan), Dörk, T. (Thilo), Santos Silva, I. (Isabel) dos, Dunning, A.M. (Alison M.), Dwek, M. (Miriam), Eccles, D.M. (Diana M.), Eliassen, A.H. (A. Heather), Engel, C. (Christoph), Eriksson, M. (Mikael), Evans, D.G. (D. Gareth), Fasching, P.A. (Peter), Flyger, H. (Henrik), Fostira, F. (Florentia), Friedman, E. (Eitan), Fritschi, L. (Lin), Frost, D. (Debra), Gago-Dominguez, M. (Manuela), Gapstur, S.M. (Susan M.), Garber, J. (Judy), Garcia-Barberan, V. (Vanesa), García-Closas, M. (Montserrat), García-Sáenz, J.A. (José A.), Gaudet, M.M. (Mia M.), Gayther, S.A. (Simon), Gehrig, A. (Andrea), Georgoulias, V. (Vassilios), Giles, G.G. (Graham G.), Godwin, A.K. (Andrew K.), Goldberg, M.S. (Mark), Radice, P. (Paolo), González-Neira, A. (Anna), Greene, M.H. (Mark H.), Guénel, P. (Pascal), Haeberle, L. (Lothar), Hahnen, E. (Eric), Haiman, C.A. (Christopher), Håkansson, N. (Niclas), Hall, P. (Per), Hamann, U. (Ute), Harrington, P.A. (Patricia A.), Hart, S.N. (Steven N.), He, W. (Wei), Hogervorst, F.B.L. (Frans B. L.), Hollestelle, A. (Antoinette), Hopper, J.L. (John), Horcasitas, D.J. (Darling J.), Hulick, P.J. (Peter J.), Hunter, D.J. (David J.), Imyanitov, E.N. (Evgeny), Fox, S.B. (Stephen), Campbell, I. (Ian), Spurdle, A. (Amanda), Webb, P. (Penny), De Fazio, A. (Anna), Tassell, M. (Margaret), Kirk, J. (Judy), Lindeman, G.J. (Geoffrey), Price, M. (Melanie), Southey, M.C. (Melissa), Milne, R.L. (Roger), Deb, S. (Sid), Bowtell, D. (David), Hout, A.H. (Annemarie) van der, Ouweland, A.M.W. (Ans) van den, Mensenkamp, A.R. (Arjen R.), Deurzen, C.H.M. (Carolien) van, Kets, C.M. (Marleen), Seynaeve, C.M. (Caroline), van Asperen, C.J. (Christi J.), Aalfs, C.M. (Cora), Gómez Garcia, E.B. (Encarna B.), Leeuwen, F.E. (Flora) van, Bock, G.H. (Geertruida) de, Meijers-Heijboer, E.J. (Hanne), Obdeijn, A.I.M. (Inge-Marie), Gille, J.J.P. (J. J.P.), Oosterwijk, J.C. (Jan), Wijnen, J.T. (Juul), Kolk, L.E. (Lizet) van der, Hooning, M.J. (Maartje), Ausems, M.G.E.M. (Margreet), Mourits, M.J. (Marjan), Blok, M.J. (Marinus J.), Rookus, M.A. (Matti), van der Luijt, R.B. (Rob B.), Cronenburg, T.C.T.E.F. van, Pol, C. (Carmen) van der, Russell, N.S. (Nicola), Siesling, S. (Sabine), Overbeek, L.I.H. (Lucy), Wijnands, R. (R.), Lange, J.L. (J.) de, Clarke, C. (Christine), Graham, D. (Dinny), Sachchithananthan, M. (Mythily), Marsh, D. (Deborah), Scott, R.J. (Rodney), Baxter, R. (Robert), Yip, D. (Desmond), Carpenter, T.A. (Adrian), Davis, A. (Alison), Pathmanathan, N. (Nirmala), Simpson, P. (Peter), Jager, A. (Agnes), Jakubowska, A. (Anna), James, M. (Margaret), Jensen, U.B. (Uffe Birk), John, E.M. (Esther), Jones, M.E. (Michael E.), Kaaks, R. (Rudolf), Kapoor, P.M. (Pooja Middha), Karlan, B.Y. (Beth), Keeman, R. (Renske), Khusnutdinova, E.K. (Elza), Kiiski, J.I. (Johanna I.), Ko, Y.-D. (Yon-Dschun), Kosma, V.-M. (Veli-Matti), Kraft, P. (Peter), Kurian, A.W. (Allison W.), Laitman, Y. (Yael), Lambrechts, D. (Diether), Le Marchand, L. (Loic), Lester, J. (Jenny), Lesueur, F. (Fabienne), Lindstrom, T. (Tricia), Lopez-Fernández, A. (Adria), Loud, J.T. (Jennifer T.), Luccarini, C. (Craig), Mannermaa, A. (Arto), Manoukian, S. (Siranoush), Margolin, S. (Sara), Martens, J.W.M. (John), Mebirouk, N. (Noura), Meindl, A. (Alfons), Miller, A. (Austin), Milne, R.L. (Roger L.), Montagna, M. (Marco), Nathanson, K.L. (Katherine), Floris, O.A.M., Nevanlinna, H. (Heli), Nielsen, F.C. (Finn C.), O’Brien, K.M. (Katie M.), Olopade, O.I. (Olofunmilayo), Olson, J.E. (Janet), Olsson, H. (Håkan), Osorio, A. (Ana), Ottini, L. (Laura), Park-Simon, T.-W. (Tjoung-Won), Parsons, M. (Marilyn), Pedersen, I.S. (Inge Sokilde), Peshkin, B. (Beth), Peterlongo, P. (Paolo), Peto, J. (Julian), Pharoah, P.D.P. (Paul), Phillips, K.-A. (Kelly-Anne), Polley, E.C. (Eric C.), Poppe, B. (Bruce), Presneau, N. (Nadege), Pujana, M.A. (Miquel Angel), Punie, K. (Kevin), Rantala, J. (Johanna), Rashid, M.U. (Muhammad), Rennert, G. (Gad), Rennert, H.S. (Hedy S.), Robson, M. (Mark), Romero, A. (Atocha), Rossing, M. (Maria), Saloustros, E. (Emmanouil), Sandler, D.P. (Dale P.), Santella, R.M. (Regina), Scheuner, M.T. (Maren T.), Schmidt, M.K. (Marjanka K.), Schmidt, G. (Gunnar), Scott, C. (Christopher), Sharma, P. (Priyanka), Soucy, P. (Penny), Southey, M.C. (Melissa C.), Spinelli, J.J. (John J.), Steinsnyder, Z. (Zoe), Stone, J. (Jennifer), Stoppa-Lyonnet, D. (Dominique), Swerdlow, A.J. (Anthony ), Tamimi, R. (Rulla), Tapper, W.J. (William J.), Taylor, J.A. (Jack A.), Terry, M.B. (Mary Beth), Teulé, A. (Alex), Thull, D.L. (Darcy L.), Tischkowitz, M. (Marc), Toland, A.E. (Amanda), Torres, D. (Diana), Trainer, A.H. (Alison H.), Truong, T. (Thérèse), Tung, N. (Nadine), Vachon, C. (Celine), Vega, A. (Ana), Joseph, V. (Vijai), Wang, Q. (Qin), Wappenschmidt, B. (Barbara), Weinberg, C.R. (Clarice R.), Weitzel, J.N. (Jeffrey), Wendt, C. (Camilla), Wolk, K. (Kerstin), Yadav, S. (Siddhartha), Yang, X.R. (Xiaohong R.), Yannoukakos, D. (Drakoulis), Zheng, W. (Wei), Ziogas, A. (Argyrios), Zorn, K.K. (Kristin K.), Park, S.K. (Sue K.), Thomassen, M. (Mads), Offit, K. (Kenneth), Schmutzler, R.K. (Rita), Couch, F.J. (Fergus), Simard, J. (Jacques), Chenevix-Trench, G. (Georgia), Adamo, P. (Pio) d', Andrieu, N. (Nadine), Antoniou, A.C. (Antonis C.), Coignard, J. (Juliette), Lush, M. (Michael), Beesley, J. (Jonathan), O’Mara, T.A. (Tracy A.), Dennis, J. (Joe), Tyrer, J.P. (Jonathan P.), Barnes, D. (Daniel), McGuffog, L. (Lesley), Leslie, G. (Goska), Bolla, M.K. (Manjeet K.), Adank, M.A. (Muriel), Agata, S. (Simona), Ahearn, T. (Thomas), Aittomäki, K. (Kristiina), Andrulis, I.L. (Irene L.), Anton-Culver, H. (Hoda), Arndt, V. (Volker), Arnold, N. (Norbert), Aronson, K.J. (Kristan J.), Arun, B.K. (Banu), Augustinsson, A. (Annelie), Azzollini, J., Barrowdale, D. (Daniel), Baynes, C. (Caroline), Becher, H. (Heko), Bermisheva, M. (Marina), Bernstein, L. (Leslie), Białkowska, K. (Katarzyna), Blomqvist, C. (Carl), Bojesen, S.E. (Stig), Bonnani, B. (Bernardo), Borg, Å. (Åke), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Burwinkel, B. (Barbara), Buys, S.S. (Saundra S.), Caldes, T. (Trinidad), Caligo, M.A. (Maria A.), Campa, D. (Daniele), Carter, B.D. (Brian D.), Castelao, J.E. (Jose ), Chang-Claude, J. (Jenny), Chanock, S.J. (Stephen J.), Chung, W.K. (Wendy K.), Claes, K.B.M. (Kathleen B. M.), Clarke, C.L. (Christine L.), Bertrand, O. (Ophélie), Caputo, S. (Sandrine), Dupré, A. (Anaïs), Le Mentec, M. (Marine), Belotti, M. (Muriel), Birot, A.-M. (Anne-Marie), Buecher, B. (Bruno), Fourme, E. (Emmanuelle), Gauthier-Villars, M. (Marion), Golmard, L. (Lisa), Houdayer, C. (Claude), Moncoutier, V. (Virginie), de Pauw, A. (Antoine), Saule, C. (Claire), Sinilnikova, O. (Olga), Mazoyer, S. (Sylvie), Damiola, F. (Francesca), Barjhoux, L. (Laure), Verny-Pierre, C. (Carole), Léone, M. (Mélanie), Boutry-Kryza, N. (N.), Calender, A. (Alain), Giraud, S. (Sophie), Caron, O. (Olivier), Guillaud-Bataille, M. (Marine), Bressac-de Paillerets, B. (Brigitte), Bignon, Y.-J. (Yves-Jean), Uhrhammer, N. (Nancy), Lasset, C. (Christine), Bonadona, V. (Valérie), Berthet, P. (Pascaline), Vaur, D. (Dominique), Castera, L. (Laurent), Noguchi, T. (Tetsuro), Popovici, C. (Cornel), Sobol, H. (Hagay), Bourdon, V. (Violaine), Remenieras, A. (Audrey), Nogues, C. (Catherine), Coupier, I. (Isabelle), Pujol, P. (Pascal), Dumont, A. (Aurélie), Révillion, F. (Françoise), Adenis, C. (Claude), Muller, D.W. (Danièle), Barouk-Simonet, E. (Emmanuelle), Bonnet, F. (Françoise), Bubien, V. (Virginie), Sevenet, N. (Nicolas), Longy, M. (Michel), Toulas, C. (Christine), Guimbaud, R. (Rosine), Gladieff, L. (Laurence), Feillel, V. (Viviane), Leroux, D. (Dominique), Dreyfus, H. (Hélène), Rebischung, C. (Christine), Peysselon, M. (Magalie), Coron, F. (Fanny), Faivre, L. (Laurence), Baurand, A. (Amandine), Jacquot, C. (Caroline), Bertolone, G. (Geoffrey), Lizard, S. (Sarab), Prieur, F. (Fabienne), Lebrun, M. (Marine), Kientz, C. (Caroline), Ferrer, S.F., Mari, V. (Véronique), Vénat-Bouvet, L. (Laurence), Delnatte, C. (Capucine), Bézieau, S. (Stéphane), Mortemousque, I. (Isabelle), Coulet, F. (Florence), Colas, C. (Chrystelle), Soubrier, F. (Florent), Warcoin, M. (Mathilde), Sokolowska, J. (Johanna), Bronner, M. (Myriam), Collonge-Rame, M.-A., Damette, A. (Alexandre), Gesta, P. (Paul), Lallaoui, H. (Hakima), Chiesa, J. (Jean), Molina-Gomes, D. (Denise), Ingster, O. (Olivier), Gregory, H. (Helen), Miedzybrodzka, Z. (Zosia), Morrison, P.J. (Patrick J.), Ong, K.-R. (Kai-ren), Donaldson, A. (Alan), Rogers, M.T. (Mark), Kennedy, M.J. (M. John), Porteous, M.E. (Mary), Brewer, C. (Carole), Davidson, R. (Rosemarie), Izatt, L. (Louise), Brady, A. (A.), Barwell, J. (Julian), Adlard, J.W. (Julian), Foo, C. (Claire), Lalloo, F. (Fiona), Side, L.E. (Lucy E.), Eason, J. (Jacqueline), Henderson, A. (Alex), Walker, L. (Lisa), Eeles, R. (Rosalind), Cook, J. (Jackie), Snape, K. (Katie), Eccles, D. (Diana), Murray, A. (Alexandra), McCann, E. (Emma), Collée, J.M. (J. Margriet), Conroy, D.M. (Don M.), Czene, K. (Kamila), Daly, M.B. (Mary B.), Devilee, P. (Peter), Diez, O. (Orland), Ding, Y.C. (Yuan Chun), Domchek, S.M. (Susan), Dörk, T. (Thilo), Santos Silva, I. (Isabel) dos, Dunning, A.M. (Alison M.), Dwek, M. (Miriam), Eccles, D.M. (Diana M.), Eliassen, A.H. (A. Heather), Engel, C. (Christoph), Eriksson, M. (Mikael), Evans, D.G. (D. Gareth), Fasching, P.A. (Peter), Flyger, H. (Henrik), Fostira, F. (Florentia), Friedman, E. (Eitan), Fritschi, L. (Lin), Frost, D. (Debra), Gago-Dominguez, M. (Manuela), Gapstur, S.M. (Susan M.), Garber, J. (Judy), Garcia-Barberan, V. (Vanesa), García-Closas, M. (Montserrat), García-Sáenz, J.A. (José A.), Gaudet, M.M. (Mia M.), Gayther, S.A. (Simon), Gehrig, A. (Andrea), Georgoulias, V. (Vassilios), Giles, G.G. (Graham G.), Godwin, A.K. (Andrew K.), Goldberg, M.S. (Mark), Radice, P. (Paolo), González-Neira, A. (Anna), Greene, M.H. (Mark H.), Guénel, P. (Pascal), Haeberle, L. (Lothar), Hahnen, E. (Eric), Haiman, C.A. (Christopher), Håkansson, N. (Niclas), Hall, P. (Per), Hamann, U. (Ute), Harrington, P.A. (Patricia A.), Hart, S.N. (Steven N.), He, W. (Wei), Hogervorst, F.B.L. (Frans B. L.), Hollestelle, A. (Antoinette), Hopper, J.L. (John), Horcasitas, D.J. (Darling J.), Hulick, P.J. (Peter J.), Hunter, D.J. (David J.), Imyanitov, E.N. (Evgeny), Fox, S.B. (Stephen), Campbell, I. (Ian), Spurdle, A. (Amanda), Webb, P. (Penny), De Fazio, A. (Anna), Tassell, M. (Margaret), Kirk, J. (Judy), Lindeman, G.J. (Geoffrey), Price, M. (Melanie), Southey, M.C. (Melissa), Milne, R.L. (Roger), Deb, S. (Sid), Bowtell, D. (David), Hout, A.H. (Annemarie) van der, Ouweland, A.M.W. (Ans) van den, Mensenkamp, A.R. (Arjen R.), Deurzen, C.H.M. (Carolien) van, Kets, C.M. (Marleen), Seynaeve, C.M. (Caroline), van Asperen, C.J. (Christi J.), Aalfs, C.M. (Cora), Gómez Garcia, E.B. (Encarna B.), Leeuwen, F.E. (Flora) van, Bock, G.H. (Geertruida) de, Meijers-Heijboer, E.J. (Hanne), Obdeijn, A.I.M. (Inge-Marie), Gille, J.J.P. (J. J.P.), Oosterwijk, J.C. (Jan), Wijnen, J.T. (Juul), Kolk, L.E. (Lizet) van der, Hooning, M.J. (Maartje), Ausems, M.G.E.M. (Margreet), Mourits, M.J. (Marjan), Blok, M.J. (Marinus J.), Rookus, M.A. (Matti), van der Luijt, R.B. (Rob B.), Cronenburg, T.C.T.E.F. van, Pol, C. (Carmen) van der, Russell, N.S. (Nicola), Siesling, S. (Sabine), Overbeek, L.I.H. (Lucy), Wijnands, R. (R.), Lange, J.L. (J.) de, Clarke, C. (Christine), Graham, D. (Dinny), Sachchithananthan, M. (Mythily), Marsh, D. (Deborah), Scott, R.J. (Rodney), Baxter, R. (Robert), Yip, D. (Desmond), Carpenter, T.A. (Adrian), Davis, A. (Alison), Pathmanathan, N. (Nirmala), Simpson, P. (Peter), Jager, A. (Agnes), Jakubowska, A. (Anna), James, M. (Margaret), Jensen, U.B. (Uffe Birk), John, E.M. (Esther), Jones, M.E. (Michael E.), Kaaks, R. (Rudolf), Kapoor, P.M. (Pooja Middha), Karlan, B.Y. (Beth), Keeman, R. (Renske), Khusnutdinova, E.K. (Elza), Kiiski, J.I. (Johanna I.), Ko, Y.-D. (Yon-Dschun), Kosma, V.-M. (Veli-Matti), Kraft, P. (Peter), Kurian, A.W. (Allison W.), Laitman, Y. (Yael), Lambrechts, D. (Diether), Le Marchand, L. (Loic), Lester, J. (Jenny), Lesueur, F. (Fabienne), Lindstrom, T. (Tricia), Lopez-Fernández, A. (Adria), Loud, J.T. (Jennifer T.), Luccarini, C. (Craig), Mannermaa, A. (Arto), Manoukian, S. (Siranoush), Margolin, S. (Sara), Martens, J.W.M. (John), Mebirouk, N. (Noura), Meindl, A. (Alfons), Miller, A. (Austin), Milne, R.L. (Roger L.), Montagna, M. (Marco), Nathanson, K.L. (Katherine), Floris, O.A.M., Nevanlinna, H. (Heli), Nielsen, F.C. (Finn C.), O’Brien, K.M. (Katie M.), Olopade, O.I. (Olofunmilayo), Olson, J.E. (Janet), Olsson, H. (Håkan), Osorio, A. (Ana), Ottini, L. (Laura), Park-Simon, T.-W. (Tjoung-Won), Parsons, M. (Marilyn), Pedersen, I.S. (Inge Sokilde), Peshkin, B. (Beth), Peterlongo, P. (Paolo), Peto, J. (Julian), Pharoah, P.D.P. (Paul), Phillips, K.-A. (Kelly-Anne), Polley, E.C. (Eric C.), Poppe, B. (Bruce), Presneau, N. (Nadege), Pujana, M.A. (Miquel Angel), Punie, K. (Kevin), Rantala, J. (Johanna), Rashid, M.U. (Muhammad), Rennert, G. (Gad), Rennert, H.S. (Hedy S.), Robson, M. (Mark), Romero, A. (Atocha), Rossing, M. (Maria), Saloustros, E. (Emmanouil), Sandler, D.P. (Dale P.), Santella, R.M. (Regina), Scheuner, M.T. (Maren T.), Schmidt, M.K. (Marjanka K.), Schmidt, G. (Gunnar), Scott, C. (Christopher), Sharma, P. (Priyanka), Soucy, P. (Penny), Southey, M.C. (Melissa C.), Spinelli, J.J. (John J.), Steinsnyder, Z. (Zoe), Stone, J. (Jennifer), Stoppa-Lyonnet, D. (Dominique), Swerdlow, A.J. (Anthony ), Tamimi, R. (Rulla), Tapper, W.J. (William J.), Taylor, J.A. (Jack A.), Terry, M.B. (Mary Beth), Teulé, A. (Alex), Thull, D.L. (Darcy L.), Tischkowitz, M. (Marc), Toland, A.E. (Amanda), Torres, D. (Diana), Trainer, A.H. (Alison H.), Truong, T. (Thérèse), Tung, N. (Nadine), Vachon, C. (Celine), Vega, A. (Ana), Joseph, V. (Vijai), Wang, Q. (Qin), Wappenschmidt, B. (Barbara), Weinberg, C.R. (Clarice R.), Weitzel, J.N. (Jeffrey), Wendt, C. (Camilla), Wolk, K. (Kerstin), Yadav, S. (Siddhartha), Yang, X.R. (Xiaohong R.), Yannoukakos, D. (Drakoulis), Zheng, W. (Wei), Ziogas, A. (Argyrios), Zorn, K.K. (Kristin K.), Park, S.K. (Sue K.), Thomassen, M. (Mads), Offit, K. (Kenneth), Schmutzler, R.K. (Rita), Couch, F.J. (Fergus), Simard, J. (Jacques), Chenevix-Trench, G. (Georgia), Adamo, P. (Pio) d', Andrieu, N. (Nadine), and Antoniou, A.C. (Antonis C.)
Abstract: Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers.
Published: 2021
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8. Author Correction: A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers (Nature Communications, (2021), 12, 1, (1078), 10.1038/s41467-020-20496-3).

Author: Coignard J., Lush M., Beesley J., O'Mara T.A., Dennis J., Tyrer J.P., Barnes D.R., McGuffog L., Leslie G., Bolla M.K., Agata S., Ahearn T., Aittomaki K., Andrulis I.L., Anton-Culver H., Arndt V., Arnold N., Aronson K.J., Arun B.K., Augustinsson A., Azzollini J., Barrowdale D., Baynes C., Becher H., Bermisheva M., Bernstein L., Bialkowska K., Blomqvist C., Bojesen S.E., Bonanni B., Borg A., Brauch H., Brenner H., Burwinkel B., Buys S.S., Caldes T., Caligo M.A., Campa D., Carter B.D., Castelao J.E., Chang-Claude J., Chanock S.J., Chung W.K., Claes K.B.M., Clarke C.L., Bertrand O., Caputo S., Dupre A., Le Mentec M., Belotti M., Birot A.-M., Buecher B., Fourme E., Gauthier-Villars M., Golmard L., Houdayer C., Moncoutier V., de Pauw A., Saule C., Sinilnikova O., Mazoyer S., Damiola F., Barjhoux L., Verny-Pierre C., Leone M., Boutry-Kryza N., Calender A., Giraud S., Caron O., Guillaud-Bataille M., Bressac-de-Paillerets B., Bignon Y.-J., Uhrhammer N., Lasset C., Bonadona V., Berthet P., Vaur D., Castera L., Popovici C., Sobol H., Bourdon V., Noguchi T., Remenieras A., Nogues C., Coupier I., Pujol P., Dumont A., Revillion F., Adenis C., Muller D., Barouk-Simonet E., Bonnet F., Bubien V., Sevenet N., Longy M., Toulas C., Guimbaud R., Gladieff L., Feillel V., Leroux D., Dreyfus H., Rebischung C., Peysselon M., Coron F., Faivre L., Baurand A., Jacquot C., Bertolone G., Lizard S., Prieur F., Lebrun M., Kientz C., Ferrer S.F., Mari V., Venat-Bouvet L., Delnatte C., Bezieau S., Mortemousque I., Coulet F., Colas C., Soubrier F., Warcoin M., Sokolowska J., Bronner M., Collonge-Rame M.-A., Damette A., Gesta P., Lallaoui H., Chiesa J., Molina-Gomes D., Ingster O., Gregory H., Miedzybrodzka Z., Morrison P.J., Ong K.-R., Donaldson A., Rogers M.T., Kennedy M.J., Porteous M.E., Brewer C., Davidson R., Izatt L., Brady A., Barwell J., Adlard J., Foo C., Lalloo F., Side L.E., Eason J., Henderson A., Walker L., Eeles R.A., Cook J., Snape K., Eccles D., Murray A., McCann E., Conroy D.M., Czene K., Daly M.B., Devilee P., Diez O., Ding Y.C., Domchek S.M., Dork T., dos-Santos-Silva I., Dunning A.M., Dwek M., Eccles D.M., Eliassen A.H., Engel C., Eriksson M., Evans D.G., Fasching P.A., Flyger H., Fostira F., Friedman E., Fritschi L., Frost D., Gago-Dominguez M., Gapstur S.M., Garber J., Garcia-Barberan V., Garcia-Closas M., Garcia-Saenz J.A., Gaudet M.M., Gayther S.A., Gehrig A., Georgoulias V., Giles G.G., Godwin A.K., Goldberg M.S., Goldgar D.E., Gonzalez-Neira A., Greene M.H., Guenel P., Haeberle L., Hahnen E., Haiman C.A., Hakansson N., Hall P., Hamann U., Harrington P.A., Hart S.N., He W., Hogervorst F.B.L., Hollestelle A., Hopper J.L., Horcasitas D.J., Hulick P.J., Hunter D.J., Imyanitov E.N., Fox S., Campbell I., Spurdle A., Webb P., de Fazio A., Tassell M., Kirk J., Lindeman G., Price M., Southey M., Milne R., Deb S., Bowtell D., van der Hout A.H., van den Ouweland A.M.W., Mensenkamp A.R., van Deurzen C.H.M., Kets C.M., Seynaeve C., van Asperen C.J., Aalfs C.M., Gomez Garcia E.B., van Leeuwen F.E., de Bock G.H., Meijers-Heijboer H.E.J., Obdeijn I.M., Collee J.M., Gille J.J.P., Oosterwijk J.C., Wijnen J.T., van der Kolk L.E., Hooning M.J., Ausems M.G.E.M., Mourits M.J.E., Blok M.J., Rookus M.A., Adank M.A., van der Luijt R.B., van Cronenburg T.C.T.E.F., van der Pol C.C., Russell N.S., Siesling S., Overbeek L., Wijnands R., de Lange J.L., Clarke C., Graham D., Sachchithananthan M., Marsh D., Scott R., Baxter R., Yip D., Carpenter J., Davis A., Pathmanathan N., Simpson P., Jager A., Jakubowska A., James P.A., Jensen U.B., John E.M., Jones M.E., Kaaks R., Kapoor P.M., Karlan B.Y., Keeman R., Khusnutdinova E., Kiiski J.I., Ko Y.-D., Kosma V.-M., Kraft P., Kurian A.W., Laitman Y., Lambrechts D., Le Marchand L., Lester J., Lesueur F., Lindstrom T., Lopez-Fernandez A., Loud J.T., Luccarini C., Mannermaa A., Manoukian S., Margolin S., Martens J.W.M., Mebirouk N., Meindl A., Miller A., Milne R.L., Montagna M., Nathanson K.L., Neuhausen S.L., Nevanlinna H., Nielsen F.C., O'Brien K.M., Olopade O.I., Olson J.E., Olsson H., Osorio A., Ottini L., Park-Simon T.-W., Parsons M.T., Pedersen I.S., Peshkin B., Peterlongo P., Peto J., Pharoah P.D.P., Phillips K.-A., Polley E.C., Poppe B., Presneau N., Pujana M.A., Punie K., Radice P., Rantala J., Rashid M.U., Rennert G., Rennert H.S., Robson M., Romero A., Rossing M., Saloustros E., Sandler D.P., Santella R., Scheuner M.T., Schmidt M.K., Schmidt G., Scott C., Sharma P., Soucy P., Southey M.C., Spinelli J.J., Steinsnyder Z., Stone J., Stoppa-Lyonnet D., Swerdlow A., Tamimi R.M., Tapper W.J., Taylor J.A., Terry M.B., Teule A., Thull D.L., Tischkowitz M., Toland A.E., Torres D., Trainer A.H., Truong T., Tung N., Vachon C.M., Vega A., Vijai J., Wang Q., Wappenschmidt B., Weinberg C.R., Weitzel J.N., Wendt C., Wolk A., Yadav S., Yang X.R., Yannoukakos D., Zheng W., Ziogas A., Zorn K.K., Park S.K., Thomassen M., Offit K., Schmutzler R.K., Couch F.J., Simard J., Chenevix-Trench G., Easton D.F., Andrieu N., Antoniou A.C., Coignard J., Lush M., Beesley J., O'Mara T.A., Dennis J., Tyrer J.P., Barnes D.R., McGuffog L., Leslie G., Bolla M.K., Agata S., Ahearn T., Aittomaki K., Andrulis I.L., Anton-Culver H., Arndt V., Arnold N., Aronson K.J., Arun B.K., Augustinsson A., Azzollini J., Barrowdale D., Baynes C., Becher H., Bermisheva M., Bernstein L., Bialkowska K., Blomqvist C., Bojesen S.E., Bonanni B., Borg A., Brauch H., Brenner H., Burwinkel B., Buys S.S., Caldes T., Caligo M.A., Campa D., Carter B.D., Castelao J.E., Chang-Claude J., Chanock S.J., Chung W.K., Claes K.B.M., Clarke C.L., Bertrand O., Caputo S., Dupre A., Le Mentec M., Belotti M., Birot A.-M., Buecher B., Fourme E., Gauthier-Villars M., Golmard L., Houdayer C., Moncoutier V., de Pauw A., Saule C., Sinilnikova O., Mazoyer S., Damiola F., Barjhoux L., Verny-Pierre C., Leone M., Boutry-Kryza N., Calender A., Giraud S., Caron O., Guillaud-Bataille M., Bressac-de-Paillerets B., Bignon Y.-J., Uhrhammer N., Lasset C., Bonadona V., Berthet P., Vaur D., Castera L., Popovici C., Sobol H., Bourdon V., Noguchi T., Remenieras A., Nogues C., Coupier I., Pujol P., Dumont A., Revillion F., Adenis C., Muller D., Barouk-Simonet E., Bonnet F., Bubien V., Sevenet N., Longy M., Toulas C., Guimbaud R., Gladieff L., Feillel V., Leroux D., Dreyfus H., Rebischung C., Peysselon M., Coron F., Faivre L., Baurand A., Jacquot C., Bertolone G., Lizard S., Prieur F., Lebrun M., Kientz C., Ferrer S.F., Mari V., Venat-Bouvet L., Delnatte C., Bezieau S., Mortemousque I., Coulet F., Colas C., Soubrier F., Warcoin M., Sokolowska J., Bronner M., Collonge-Rame M.-A., Damette A., Gesta P., Lallaoui H., Chiesa J., Molina-Gomes D., Ingster O., Gregory H., Miedzybrodzka Z., Morrison P.J., Ong K.-R., Donaldson A., Rogers M.T., Kennedy M.J., Porteous M.E., Brewer C., Davidson R., Izatt L., Brady A., Barwell J., Adlard J., Foo C., Lalloo F., Side L.E., Eason J., Henderson A., Walker L., Eeles R.A., Cook J., Snape K., Eccles D., Murray A., McCann E., Conroy D.M., Czene K., Daly M.B., Devilee P., Diez O., Ding Y.C., Domchek S.M., Dork T., dos-Santos-Silva I., Dunning A.M., Dwek M., Eccles D.M., Eliassen A.H., Engel C., Eriksson M., Evans D.G., Fasching P.A., Flyger H., Fostira F., Friedman E., Fritschi L., Frost D., Gago-Dominguez M., Gapstur S.M., Garber J., Garcia-Barberan V., Garcia-Closas M., Garcia-Saenz J.A., Gaudet M.M., Gayther S.A., Gehrig A., Georgoulias V., Giles G.G., Godwin A.K., Goldberg M.S., Goldgar D.E., Gonzalez-Neira A., Greene M.H., Guenel P., Haeberle L., Hahnen E., Haiman C.A., Hakansson N., Hall P., Hamann U., Harrington P.A., Hart S.N., He W., Hogervorst F.B.L., Hollestelle A., Hopper J.L., Horcasitas D.J., Hulick P.J., Hunter D.J., Imyanitov E.N., Fox S., Campbell I., Spurdle A., Webb P., de Fazio A., Tassell M., Kirk J., Lindeman G., Price M., Southey M., Milne R., Deb S., Bowtell D., van der Hout A.H., van den Ouweland A.M.W., Mensenkamp A.R., van Deurzen C.H.M., Kets C.M., Seynaeve C., van Asperen C.J., Aalfs C.M., Gomez Garcia E.B., van Leeuwen F.E., de Bock G.H., Meijers-Heijboer H.E.J., Obdeijn I.M., Collee J.M., Gille J.J.P., Oosterwijk J.C., Wijnen J.T., van der Kolk L.E., Hooning M.J., Ausems M.G.E.M., Mourits M.J.E., Blok M.J., Rookus M.A., Adank M.A., van der Luijt R.B., van Cronenburg T.C.T.E.F., van der Pol C.C., Russell N.S., Siesling S., Overbeek L., Wijnands R., de Lange J.L., Clarke C., Graham D., Sachchithananthan M., Marsh D., Scott R., Baxter R., Yip D., Carpenter J., Davis A., Pathmanathan N., Simpson P., Jager A., Jakubowska A., James P.A., Jensen U.B., John E.M., Jones M.E., Kaaks R., Kapoor P.M., Karlan B.Y., Keeman R., Khusnutdinova E., Kiiski J.I., Ko Y.-D., Kosma V.-M., Kraft P., Kurian A.W., Laitman Y., Lambrechts D., Le Marchand L., Lester J., Lesueur F., Lindstrom T., Lopez-Fernandez A., Loud J.T., Luccarini C., Mannermaa A., Manoukian S., Margolin S., Martens J.W.M., Mebirouk N., Meindl A., Miller A., Milne R.L., Montagna M., Nathanson K.L., Neuhausen S.L., Nevanlinna H., Nielsen F.C., O'Brien K.M., Olopade O.I., Olson J.E., Olsson H., Osorio A., Ottini L., Park-Simon T.-W., Parsons M.T., Pedersen I.S., Peshkin B., Peterlongo P., Peto J., Pharoah P.D.P., Phillips K.-A., Polley E.C., Poppe B., Presneau N., Pujana M.A., Punie K., Radice P., Rantala J., Rashid M.U., Rennert G., Rennert H.S., Robson M., Romero A., Rossing M., Saloustros E., Sandler D.P., Santella R., Scheuner M.T., Schmidt M.K., Schmidt G., Scott C., Sharma P., Soucy P., Southey M.C., Spinelli J.J., Steinsnyder Z., Stone J., Stoppa-Lyonnet D., Swerdlow A., Tamimi R.M., Tapper W.J., Taylor J.A., Terry M.B., Teule A., Thull D.L., Tischkowitz M., Toland A.E., Torres D., Trainer A.H., Truong T., Tung N., Vachon C.M., Vega A., Vijai J., Wang Q., Wappenschmidt B., Weinberg C.R., Weitzel J.N., Wendt C., Wolk A., Yadav S., Yang X.R., Yannoukakos D., Zheng W., Ziogas A., Zorn K.K., Park S.K., Thomassen M., Offit K., Schmutzler R.K., Couch F.J., Simard J., Chenevix-Trench G., Easton D.F., Andrieu N., and Antoniou A.C.
Abstract: The original version of this Article contained an error in the spelling of the author Heiko Becher, which was incorrectly given as Heko Becher. This has now been corrected in both the PDF and HTML versions of the Article.Copyright © 2021, The Author(s).
Published: 2021

9. Erratum: Author Correction: A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers (Nature communications (2021) 12 1 (1078)).

Author: Coignard J., Lush M., Beesley J., O'Mara T.A., Dennis J., Tyrer J.P., Barnes D.R., McGuffog L., Leslie G., Bolla M.K., Adank M.A., Agata S., Ahearn T., Aittomaki K., Andrulis I.L., Anton-Culver H., Arndt V., Arnold N., Aronson K.J., Arun B.K., Augustinsson A., Azzollini J., Barrowdale D., Baynes C., Becher H., Bermisheva M., Bernstein L., Bialkowska K., Blomqvist C., Bojesen S.E., Bonanni B., Borg A., Brauch H., Brenner H., Burwinkel B., Buys S.S., Caldes T., Caligo M.A., Campa D., Carter B.D., Castelao J.E., Chang-Claude J., Chanock S.J., Chung W.K., Claes K.B.M., Clarke C.L., Collee J.M., Conroy D.M., Czene K., Daly M.B., Devilee P., Diez O., Ding Y.C., Domchek S.M., Dork T., Dos-Santos-Silva I., Dunning A.M., Dwek M., Eccles D.M., Eliassen A.H., Engel C., Eriksson M., Evans D.G., Fasching P.A., Flyger H., Fostira F., Friedman E., Fritschi L., Frost D., Gago-Dominguez M., Gapstur S.M., Garber J., Garcia-Barberan V., Garcia-Closas M., Garcia-Saenz J.A., Gaudet M.M., Gayther S.A., Gehrig A., Georgoulias V., Giles G.G., Godwin A.K., Goldberg M.S., Goldgar D.E., Gonzalez-Neira A., Greene M.H., Guenel P., Haeberle L., Hahnen E., Haiman C.A., Hakansson N., Hall P., Hamann U., Harrington P.A., Hart S.N., He W., Hogervorst F.B.L., Hollestelle A., Hopper J.L., Horcasitas D.J., Hulick P.J., Hunter D.J., Imyanitov E.N., Jager A., Jakubowska A., James P.A., Jensen U.B., John E.M., Jones M.E., Kaaks R., Kapoor P.M., Karlan B.Y., Keeman R., Khusnutdinova E., Kiiski J.I., Ko Y.-D., Kosma V.-M., Kraft P., Kurian A.W., Laitman Y., Lambrechts D., Le Marchand L., Lester J., Lesueur F., Lindstrom T., Lopez-Fernandez A., Loud J.T., Luccarini C., Mannermaa A., Manoukian S., Margolin S., Martens J.W.M., Mebirouk N., Meindl A., Miller A., Milne R.L., Montagna M., Nathanson K.L., Neuhausen S.L., Nevanlinna H., Nielsen F.C., O'Brien K.M., Olopade O.I., Olson J.E., Olsson H., Osorio A., Ottini L., Park-Simon T.-W., Parsons M.T., Pedersen I.S., Peshkin B., Peterlongo P., Peto J., Pharoah P.D.P., Phillips K.-A., Polley E.C., Poppe B., Presneau N., Pujana M.A., Punie K., Radice P., Rantala J., Rashid M.U., Rennert G., Rennert H.S., Robson M., Romero A., Rossing M., Saloustros E., Sandler D.P., Santella R., Scheuner M.T., Schmidt M.K., Schmidt G., Scott C., Sharma P., Soucy P., Southey M.C., Spinelli J.J., Steinsnyder Z., Stone J., Stoppa-Lyonnet D., Swerdlow A., Tamimi R.M., Tapper W.J., Taylor J.A., Terry M.B., Teule A., Thull D.L., Tischkowitz M., Toland A.E., Torres D., Trainer A.H., Truong T., Tung N., Vachon C.M., Vega A., Vijai J., Wang Q., Wappenschmidt B., Weinberg C.R., Weitzel J.N., Wendt C., Wolk A., Yadav S., Yang X.R., Yannoukakos D., Zheng W., Ziogas A., Zorn K.K., Park S.K., Thomassen M., Offit K., Schmutzler R.K., Couch F.J., Simard J., Chenevix-Trench G., Easton D.F., Andrieu N., Antoniou A.C., Coignard J., Lush M., Beesley J., O'Mara T.A., Dennis J., Tyrer J.P., Barnes D.R., McGuffog L., Leslie G., Bolla M.K., Adank M.A., Agata S., Ahearn T., Aittomaki K., Andrulis I.L., Anton-Culver H., Arndt V., Arnold N., Aronson K.J., Arun B.K., Augustinsson A., Azzollini J., Barrowdale D., Baynes C., Becher H., Bermisheva M., Bernstein L., Bialkowska K., Blomqvist C., Bojesen S.E., Bonanni B., Borg A., Brauch H., Brenner H., Burwinkel B., Buys S.S., Caldes T., Caligo M.A., Campa D., Carter B.D., Castelao J.E., Chang-Claude J., Chanock S.J., Chung W.K., Claes K.B.M., Clarke C.L., Collee J.M., Conroy D.M., Czene K., Daly M.B., Devilee P., Diez O., Ding Y.C., Domchek S.M., Dork T., Dos-Santos-Silva I., Dunning A.M., Dwek M., Eccles D.M., Eliassen A.H., Engel C., Eriksson M., Evans D.G., Fasching P.A., Flyger H., Fostira F., Friedman E., Fritschi L., Frost D., Gago-Dominguez M., Gapstur S.M., Garber J., Garcia-Barberan V., Garcia-Closas M., Garcia-Saenz J.A., Gaudet M.M., Gayther S.A., Gehrig A., Georgoulias V., Giles G.G., Godwin A.K., Goldberg M.S., Goldgar D.E., Gonzalez-Neira A., Greene M.H., Guenel P., Haeberle L., Hahnen E., Haiman C.A., Hakansson N., Hall P., Hamann U., Harrington P.A., Hart S.N., He W., Hogervorst F.B.L., Hollestelle A., Hopper J.L., Horcasitas D.J., Hulick P.J., Hunter D.J., Imyanitov E.N., Jager A., Jakubowska A., James P.A., Jensen U.B., John E.M., Jones M.E., Kaaks R., Kapoor P.M., Karlan B.Y., Keeman R., Khusnutdinova E., Kiiski J.I., Ko Y.-D., Kosma V.-M., Kraft P., Kurian A.W., Laitman Y., Lambrechts D., Le Marchand L., Lester J., Lesueur F., Lindstrom T., Lopez-Fernandez A., Loud J.T., Luccarini C., Mannermaa A., Manoukian S., Margolin S., Martens J.W.M., Mebirouk N., Meindl A., Miller A., Milne R.L., Montagna M., Nathanson K.L., Neuhausen S.L., Nevanlinna H., Nielsen F.C., O'Brien K.M., Olopade O.I., Olson J.E., Olsson H., Osorio A., Ottini L., Park-Simon T.-W., Parsons M.T., Pedersen I.S., Peshkin B., Peterlongo P., Peto J., Pharoah P.D.P., Phillips K.-A., Polley E.C., Poppe B., Presneau N., Pujana M.A., Punie K., Radice P., Rantala J., Rashid M.U., Rennert G., Rennert H.S., Robson M., Romero A., Rossing M., Saloustros E., Sandler D.P., Santella R., Scheuner M.T., Schmidt M.K., Schmidt G., Scott C., Sharma P., Soucy P., Southey M.C., Spinelli J.J., Steinsnyder Z., Stone J., Stoppa-Lyonnet D., Swerdlow A., Tamimi R.M., Tapper W.J., Taylor J.A., Terry M.B., Teule A., Thull D.L., Tischkowitz M., Toland A.E., Torres D., Trainer A.H., Truong T., Tung N., Vachon C.M., Vega A., Vijai J., Wang Q., Wappenschmidt B., Weinberg C.R., Weitzel J.N., Wendt C., Wolk A., Yadav S., Yang X.R., Yannoukakos D., Zheng W., Ziogas A., Zorn K.K., Park S.K., Thomassen M., Offit K., Schmutzler R.K., Couch F.J., Simard J., Chenevix-Trench G., Easton D.F., Andrieu N., and Antoniou A.C.
Abstract: A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-23162-4.
Published: 2021

10. Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants.

Author: Gesta P., Mulligan A.M., Nathanson K.L., Neuhausen S.L., Nevanlinna H., Niederacher D., Nielsen F.C., Nikitina-Zake L., Nogues C., Olah E., Olopade O.I., Ong K.-R., O'Shaughnessy-Kirwan A., Osorio A., Ott C.-E., Papi L., Park S.K., Parsons M.T., Pedersen I.S., Peissel B., Peixoto A., Peterlongo P., Pfeiler G., Phillips K.-A., Prajzendanc K., Pujana M.A., Radice P., Ramser J., Ramus S.J., Rantala J., Rennert G., Risch H.A., Robson M., Ronlund K., Salani R., Schuster H., Senter L., Shah P.D., Sharma P., Side L.E., Singer C.F., Slavin T.P., Soucy P., Southey M.C., Spurdle A.B., Steinemann D., Steinsnyder Z., Stoppa-Lyonnet D., Sutter C., Tan Y.Y., Teixeira M.R., Teo S.H., Thull D.L., Tischkowitz M., Tognazzo S., Toland A.E., Trainer A.H., Tung N., van Engelen K., van Rensburg E.J., Vega A., Vierstraete J., Wagner G., Walker L., Wang-Gohrke S., Wappenschmidt B., Weitzel J.N., Yadav S., Yang X., Yannoukakos D., Zimbalatti D., Offit K., Thomassen M., Couch F.J., Schmutzler R.K., Simard J., Easton D.F., Antoniou A.C., GEMO Study Collaborators, EMBRACE Collaborators, kConFab Investigators, HEBON Investigators, GENEPSO Investigators, Barnes D.R., Rookus M.A., McGuffog L., Leslie G., Mooij T.M., Dennis J., Mavaddat N., Aittomaki K., Andrulis I.L., Arnold N., Arun B.K., Azzollini J., Balmana J., Barkardottir R.B., Benitez J., Bialkowska K., Blanco A.M., Blok M.J., Bonanni B., Boonen S.E., Borg A., Bozsik A., Bradbury A.R., Brunet J., Buys S.S., Caldes T., Caligo M.A., Campbell I., Christensen L.L., Chung W.K., Claes K.B.M., Berthet P., Colas C., Adlard J., Ahmed M., Antoniou A., Barrowdale D., Brennan P., Brewer C., Easton D., Evans D.G., Side L., Collonge-Rame M.-A., Cook J., Daly M.B., Davidson R., de la Hoya M., de Putter R., Delnatte C., Diez O., Ding Y.C., Domchek S.M., Dorfling C.M., Dumont M., Eeles R., Ejlertsen B., Engel C., Faivre L., Foretova L., Fostira F., Friedlander M., Friedman E., Frost D., Ganz P.A., Garber J., Gehrig A., Gerdes A.-M., Giraud S., Glendon G., Godwin A.K., Goldgar D.E., Gonzalez-Neira A., Greene M.H., Gschwantler-Kaulich D., Hahnen E., Hamann U., Hanson H., Hentschel J., Hogervorst F.B.L., Hooning M.J., Horvath J., Hu C., Hulick P.J., Imyanitov E.N., Chenevix-Trench G., Spurdle A., Blok M., Devilee P., Hogervorst F., Hooning M., Mensenkamp A., Meijers-Heijboer H., Rookus M., Engelen K., Andrieu N., Isaacs C., Izatt L., Izquierdo A., Jakubowska A., James P.A., Janavicius R., John E.M., Joseph V., Karlan B.Y., Kast K., Koudijs M., Kruse T.A., Kwong A., Laitman Y., Lasset C., Lazaro C., Lester J., Lesueur F., Liljegren A., Loud J.T., Lubinski J., Mai P.L., Manoukian S., Mari V., Mebirouk N., Meijers-Heijboer H.E.J., Meindl A., Mensenkamp A.R., Miller A., Montagna M., Mouret-Fourme E., Mukherjee S., Gesta P., Mulligan A.M., Nathanson K.L., Neuhausen S.L., Nevanlinna H., Niederacher D., Nielsen F.C., Nikitina-Zake L., Nogues C., Olah E., Olopade O.I., Ong K.-R., O'Shaughnessy-Kirwan A., Osorio A., Ott C.-E., Papi L., Park S.K., Parsons M.T., Pedersen I.S., Peissel B., Peixoto A., Peterlongo P., Pfeiler G., Phillips K.-A., Prajzendanc K., Pujana M.A., Radice P., Ramser J., Ramus S.J., Rantala J., Rennert G., Risch H.A., Robson M., Ronlund K., Salani R., Schuster H., Senter L., Shah P.D., Sharma P., Side L.E., Singer C.F., Slavin T.P., Soucy P., Southey M.C., Spurdle A.B., Steinemann D., Steinsnyder Z., Stoppa-Lyonnet D., Sutter C., Tan Y.Y., Teixeira M.R., Teo S.H., Thull D.L., Tischkowitz M., Tognazzo S., Toland A.E., Trainer A.H., Tung N., van Engelen K., van Rensburg E.J., Vega A., Vierstraete J., Wagner G., Walker L., Wang-Gohrke S., Wappenschmidt B., Weitzel J.N., Yadav S., Yang X., Yannoukakos D., Zimbalatti D., Offit K., Thomassen M., Couch F.J., Schmutzler R.K., Simard J., Easton D.F., Antoniou A.C., GEMO Study Collaborators, EMBRACE Collaborators, kConFab Investigators, HEBON Investigators, GENEPSO Investigators, Barnes D.R., Rookus M.A., McGuffog L., Leslie G., Mooij T.M., Dennis J., Mavaddat N., Aittomaki K., Andrulis I.L., Arnold N., Arun B.K., Azzollini J., Balmana J., Barkardottir R.B., Benitez J., Bialkowska K., Blanco A.M., Blok M.J., Bonanni B., Boonen S.E., Borg A., Bozsik A., Bradbury A.R., Brunet J., Buys S.S., Caldes T., Caligo M.A., Campbell I., Christensen L.L., Chung W.K., Claes K.B.M., Berthet P., Colas C., Adlard J., Ahmed M., Antoniou A., Barrowdale D., Brennan P., Brewer C., Easton D., Evans D.G., Side L., Collonge-Rame M.-A., Cook J., Daly M.B., Davidson R., de la Hoya M., de Putter R., Delnatte C., Diez O., Ding Y.C., Domchek S.M., Dorfling C.M., Dumont M., Eeles R., Ejlertsen B., Engel C., Faivre L., Foretova L., Fostira F., Friedlander M., Friedman E., Frost D., Ganz P.A., Garber J., Gehrig A., Gerdes A.-M., Giraud S., Glendon G., Godwin A.K., Goldgar D.E., Gonzalez-Neira A., Greene M.H., Gschwantler-Kaulich D., Hahnen E., Hamann U., Hanson H., Hentschel J., Hogervorst F.B.L., Hooning M.J., Horvath J., Hu C., Hulick P.J., Imyanitov E.N., Chenevix-Trench G., Spurdle A., Blok M., Devilee P., Hogervorst F., Hooning M., Mensenkamp A., Meijers-Heijboer H., Rookus M., Engelen K., Andrieu N., Isaacs C., Izatt L., Izquierdo A., Jakubowska A., James P.A., Janavicius R., John E.M., Joseph V., Karlan B.Y., Kast K., Koudijs M., Kruse T.A., Kwong A., Laitman Y., Lasset C., Lazaro C., Lester J., Lesueur F., Liljegren A., Loud J.T., Lubinski J., Mai P.L., Manoukian S., Mari V., Mebirouk N., Meijers-Heijboer H.E.J., Meindl A., Mensenkamp A.R., Miller A., Montagna M., Mouret-Fourme E., and Mukherjee S.
Abstract: Purpose: We assessed the associations between population-based polygenic risk scores (PRS) for breast (BC) or epithelial ovarian cancer (EOC) with cancer risks for BRCA1 and BRCA2 pathogenic variant carriers. Method(s): Retrospective cohort data on 18,935 BRCA1 and 12,339 BRCA2 female pathogenic variant carriers of European ancestry were available. Three versions of a 313 single-nucleotide polymorphism (SNP) BC PRS were evaluated based on whether they predict overall, estrogen receptor (ER)-negative, or ER-positive BC, and two PRS for overall or high-grade serous EOC. Associations were validated in a prospective cohort. Result(s): The ER-negative PRS showed the strongest association with BC risk for BRCA1 carriers (hazard ratio [HR] per standard deviation = 1.29 [95% CI 1.25-1.33], P = 3x10-72). For BRCA2, the strongest association was with overall BC PRS (HR = 1.31 [95% CI 1.27-1.36], P = 7x10-50). HR estimates decreased significantly with age and there was evidence for differences in associations by predicted variant effects on protein expression. The HR estimates were smaller than general population estimates. The high-grade serous PRS yielded the strongest associations with EOC risk for BRCA1 (HR = 1.32 [95% CI 1.25-1.40], P = 3x10-22) and BRCA2 (HR = 1.44 [95% CI 1.30-1.60], P = 4x10-12) carriers. The associations in the prospective cohort were similar. Conclusion(s): Population-based PRS are strongly associated with BC and EOC risks for BRCA1/2 carriers and predict substantial absolute risk differences for women at PRS distribution extremes.Copyright © 2020, The Author(s).
Published: 2021

11. A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers.

Author: Radice P., Romero A., Rossing M., Saloustros E., Sandler D.P., Santella R., Scheuner M.T., Schmidt M.K., Schmidt G., Scott C., Sharma P., Soucy P., Southey M.C., Spinelli J.J., Steinsnyder Z., Stone J., Stoppa-Lyonnet D., Swerdlow A., Tamimi R.M., Tapper W.J., Taylor J.A., Terry M.B., Teule A., Thull D.L., Tischkowitz M., Toland A.E., Torres D., Trainer A.H., Truong T., Tung N., Vachon C.M., Vega A., Vijai J., Wang Q., Wappenschmidt B., Weinberg C.R., Weitzel J.N., Wendt C., Wolk A., Yadav S., Yang X.R., Yannoukakos D., Zheng W., Ziogas A., Zorn K.K., Park S.K., Thomassen M., Offit K., Schmutzler R.K., Couch F.J., Simard J., Chenevix-Trench G., Easton D.F., Andrieu N., Antoniou A.C., Coignard J., Lush M., Beesley J., O'Mara T.A., Dennis J., Tyrer J.P., Barnes D.R., McGuffog L., Leslie G., Bolla M.K., Agata S., Ahearn T., Aittomaki K., Andrulis I.L., Anton-Culver H., Arndt V., Arnold N., Aronson K.J., Arun B.K., Augustinsson A., Azzollini J., Barrowdale D., Baynes C., Becher H., Bermisheva M., Bernstein L., Bialkowska K., Blomqvist C., Bojesen S.E., Bonanni B., Borg A., Brauch H., Brenner H., Burwinkel B., Buys S.S., Caldes T., Caligo M.A., Campa D., Carter B.D., Castelao J.E., Chang-Claude J., Chanock S.J., Chung W.K., Claes K.B.M., Clarke C.L., Bertrand O., Caputo S., Dupre A., Le Mentec M., Belotti M., Birot A.-M., Buecher B., Fourme E., Gauthier-Villars M., Golmard L., Houdayer C., Moncoutier V., de Pauw A., Saule C., Sinilnikova O., Mazoyer S., Damiola F., Barjhoux L., Verny-Pierre C., Leone M., Boutry-Kryza N., Calender A., Giraud S., Caron O., Guillaud-Bataille M., Bressac-de-Paillerets B., Bignon Y.-J., Uhrhammer N., Lasset C., Bonadona V., Berthet P., Vaur D., Castera L., Popovici C., Sobol H., Bourdon V., Noguchi T., Remenieras A., Nogues C., Coupier I., Pujol P., Dumont A., Revillion F., Adenis C., Muller D., Barouk-Simonet E., Bonnet F., Bubien V., Sevenet N., Longy M., Toulas C., Guimbaud R., Gladieff L., Feillel V., Leroux D., Dreyfus H., Rebischung C., Peysselon M., Coron F., Faivre L., Baurand A., Jacquot C., Bertolone G., Lizard S., Prieur F., Lebrun M., Kientz C., Ferrer S.F., Mari V., Venat-Bouvet L., Delnatte C., Bezieau S., Mortemousque I., Coulet F., Colas C., Soubrier F., Warcoin M., Sokolowska J., Bronner M., Collonge-Rame M.-A., Damette A., Gesta P., Lallaoui H., Chiesa J., Molina-Gomes D., Ingster O., Gregory H., Miedzybrodzka Z., Morrison P.J., Ong K.-R., Donaldson A., Rogers M.T., Kennedy M.J., Porteous M.E., Brewer C., Davidson R., Izatt L., Brady A., Barwell J., Adlard J., Foo C., Lalloo F., Side L.E., Eason J., Henderson A., Walker L., Eeles R.A., Cook J., Snape K., Eccles D., Murray A., McCann E., Conroy D.M., Czene K., Daly M.B., Devilee P., Diez O., Ding Y.C., Domchek S.M., Dork T., dos-Santos-Silva I., Dunning A.M., Dwek M., Eccles D.M., Eliassen A.H., Engel C., Eriksson M., Evans D.G., Fasching P.A., Flyger H., Fostira F., Friedman E., Fritschi L., Frost D., Gago-Dominguez M., Gapstur S.M., Garber J., Garcia-Barberan V., Garcia-Closas M., Garcia-Saenz J.A., Gaudet M.M., Gayther S.A., Gehrig A., Georgoulias V., Giles G.G., Godwin A.K., Goldberg M.S., Goldgar D.E., Gonzalez-Neira A., Greene M.H., Guenel P., Haeberle L., Hahnen E., Haiman C.A., Hakansson N., Hall P., Hamann U., Harrington P.A., Hart S.N., He W., Hogervorst F.B.L., Hollestelle A., Hopper J.L., Horcasitas D.J., Hulick P.J., Hunter D.J., Imyanitov E.N., Fox S., Campbell I., Spurdle A., Webb P., de Fazio A., Tassell M., Kirk J., Lindeman G., Price M., Southey M., Milne R.L., Deb S., Bowtell D., van der Hout A.H., van den Ouweland A.M.W., Mensenkamp A.R., van Deurzen C.H.M., Kets C.M., Seynaeve C., van Asperen C.J., Aalfs C.M., Gomez Garcia E.B., van Leeuwen F.E., de Bock G.H., Meijers-Heijboer H.E.J., Obdeijn I.M., Collee J.M., Gille J.J.P., Oosterwijk J.C., Wijnen J.T., van der Kolk L.E., Hooning M.J., Ausems M.G.E.M., Mourits M.J.E., Blok M.J., Rookus M.A., Adank M.A., van der Luijt R.B., van Cronenburg T.C.T.E.F., van der Pol C.C., Russell N.S., Siesling S., Overbeek L., Wijnands R., de Lange J.L., Clarke C., Graham D., Sachchithananthan M., Marsh D., Scott R., Baxter R., Yip D., Carpenter J., Davis A., Pathmanathan N., Simpson P., Jager A., Jakubowska A., James P.A., Jensen U.B., John E.M., Jones M.E., Kaaks R., Kapoor P.M., Karlan B.Y., Keeman R., Khusnutdinova E., Kiiski J.I., Ko Y.-D., Kosma V.-M., Kraft P., Kurian A.W., Laitman Y., Lambrechts D., Le Marchand L., Lester J., Lesueur F., Lindstrom T., Lopez-Fernandez A., Loud J.T., Luccarini C., Mannermaa A., Manoukian S., Margolin S., Martens J.W.M., Mebirouk N., Meindl A., Miller A., Montagna M., Nathanson K.L., Neuhausen S.L., Nevanlinna H., Nielsen F.C., O'Brien K.M., Olopade O.I., Olson J.E., Olsson H., Osorio A., Ottini L., Park-Simon T.-W., Parsons M.T., Pedersen I.S., Peshkin B., Peterlongo P., Peto J., Pharoah P.D.P., Phillips K.-A., Polley E.C., Poppe B., Presneau N., Pujana M.A., Punie K., Rantala J., Rashid M.U., Rennert G., Rennert H.S., Robson M., Radice P., Romero A., Rossing M., Saloustros E., Sandler D.P., Santella R., Scheuner M.T., Schmidt M.K., Schmidt G., Scott C., Sharma P., Soucy P., Southey M.C., Spinelli J.J., Steinsnyder Z., Stone J., Stoppa-Lyonnet D., Swerdlow A., Tamimi R.M., Tapper W.J., Taylor J.A., Terry M.B., Teule A., Thull D.L., Tischkowitz M., Toland A.E., Torres D., Trainer A.H., Truong T., Tung N., Vachon C.M., Vega A., Vijai J., Wang Q., Wappenschmidt B., Weinberg C.R., Weitzel J.N., Wendt C., Wolk A., Yadav S., Yang X.R., Yannoukakos D., Zheng W., Ziogas A., Zorn K.K., Park S.K., Thomassen M., Offit K., Schmutzler R.K., Couch F.J., Simard J., Chenevix-Trench G., Easton D.F., Andrieu N., Antoniou A.C., Coignard J., Lush M., Beesley J., O'Mara T.A., Dennis J., Tyrer J.P., Barnes D.R., McGuffog L., Leslie G., Bolla M.K., Agata S., Ahearn T., Aittomaki K., Andrulis I.L., Anton-Culver H., Arndt V., Arnold N., Aronson K.J., Arun B.K., Augustinsson A., Azzollini J., Barrowdale D., Baynes C., Becher H., Bermisheva M., Bernstein L., Bialkowska K., Blomqvist C., Bojesen S.E., Bonanni B., Borg A., Brauch H., Brenner H., Burwinkel B., Buys S.S., Caldes T., Caligo M.A., Campa D., Carter B.D., Castelao J.E., Chang-Claude J., Chanock S.J., Chung W.K., Claes K.B.M., Clarke C.L., Bertrand O., Caputo S., Dupre A., Le Mentec M., Belotti M., Birot A.-M., Buecher B., Fourme E., Gauthier-Villars M., Golmard L., Houdayer C., Moncoutier V., de Pauw A., Saule C., Sinilnikova O., Mazoyer S., Damiola F., Barjhoux L., Verny-Pierre C., Leone M., Boutry-Kryza N., Calender A., Giraud S., Caron O., Guillaud-Bataille M., Bressac-de-Paillerets B., Bignon Y.-J., Uhrhammer N., Lasset C., Bonadona V., Berthet P., Vaur D., Castera L., Popovici C., Sobol H., Bourdon V., Noguchi T., Remenieras A., Nogues C., Coupier I., Pujol P., Dumont A., Revillion F., Adenis C., Muller D., Barouk-Simonet E., Bonnet F., Bubien V., Sevenet N., Longy M., Toulas C., Guimbaud R., Gladieff L., Feillel V., Leroux D., Dreyfus H., Rebischung C., Peysselon M., Coron F., Faivre L., Baurand A., Jacquot C., Bertolone G., Lizard S., Prieur F., Lebrun M., Kientz C., Ferrer S.F., Mari V., Venat-Bouvet L., Delnatte C., Bezieau S., Mortemousque I., Coulet F., Colas C., Soubrier F., Warcoin M., Sokolowska J., Bronner M., Collonge-Rame M.-A., Damette A., Gesta P., Lallaoui H., Chiesa J., Molina-Gomes D., Ingster O., Gregory H., Miedzybrodzka Z., Morrison P.J., Ong K.-R., Donaldson A., Rogers M.T., Kennedy M.J., Porteous M.E., Brewer C., Davidson R., Izatt L., Brady A., Barwell J., Adlard J., Foo C., Lalloo F., Side L.E., Eason J., Henderson A., Walker L., Eeles R.A., Cook J., Snape K., Eccles D., Murray A., McCann E., Conroy D.M., Czene K., Daly M.B., Devilee P., Diez O., Ding Y.C., Domchek S.M., Dork T., dos-Santos-Silva I., Dunning A.M., Dwek M., Eccles D.M., Eliassen A.H., Engel C., Eriksson M., Evans D.G., Fasching P.A., Flyger H., Fostira F., Friedman E., Fritschi L., Frost D., Gago-Dominguez M., Gapstur S.M., Garber J., Garcia-Barberan V., Garcia-Closas M., Garcia-Saenz J.A., Gaudet M.M., Gayther S.A., Gehrig A., Georgoulias V., Giles G.G., Godwin A.K., Goldberg M.S., Goldgar D.E., Gonzalez-Neira A., Greene M.H., Guenel P., Haeberle L., Hahnen E., Haiman C.A., Hakansson N., Hall P., Hamann U., Harrington P.A., Hart S.N., He W., Hogervorst F.B.L., Hollestelle A., Hopper J.L., Horcasitas D.J., Hulick P.J., Hunter D.J., Imyanitov E.N., Fox S., Campbell I., Spurdle A., Webb P., de Fazio A., Tassell M., Kirk J., Lindeman G., Price M., Southey M., Milne R.L., Deb S., Bowtell D., van der Hout A.H., van den Ouweland A.M.W., Mensenkamp A.R., van Deurzen C.H.M., Kets C.M., Seynaeve C., van Asperen C.J., Aalfs C.M., Gomez Garcia E.B., van Leeuwen F.E., de Bock G.H., Meijers-Heijboer H.E.J., Obdeijn I.M., Collee J.M., Gille J.J.P., Oosterwijk J.C., Wijnen J.T., van der Kolk L.E., Hooning M.J., Ausems M.G.E.M., Mourits M.J.E., Blok M.J., Rookus M.A., Adank M.A., van der Luijt R.B., van Cronenburg T.C.T.E.F., van der Pol C.C., Russell N.S., Siesling S., Overbeek L., Wijnands R., de Lange J.L., Clarke C., Graham D., Sachchithananthan M., Marsh D., Scott R., Baxter R., Yip D., Carpenter J., Davis A., Pathmanathan N., Simpson P., Jager A., Jakubowska A., James P.A., Jensen U.B., John E.M., Jones M.E., Kaaks R., Kapoor P.M., Karlan B.Y., Keeman R., Khusnutdinova E., Kiiski J.I., Ko Y.-D., Kosma V.-M., Kraft P., Kurian A.W., Laitman Y., Lambrechts D., Le Marchand L., Lester J., Lesueur F., Lindstrom T., Lopez-Fernandez A., Loud J.T., Luccarini C., Mannermaa A., Manoukian S., Margolin S., Martens J.W.M., Mebirouk N., Meindl A., Miller A., Montagna M., Nathanson K.L., Neuhausen S.L., Nevanlinna H., Nielsen F.C., O'Brien K.M., Olopade O.I., Olson J.E., Olsson H., Osorio A., Ottini L., Park-Simon T.-W., Parsons M.T., Pedersen I.S., Peshkin B., Peterlongo P., Peto J., Pharoah P.D.P., Phillips K.-A., Polley E.C., Poppe B., Presneau N., Pujana M.A., Punie K., Rantala J., Rashid M.U., Rennert G., Rennert H.S., and Robson M.
Abstract: Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10-8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers.Copyright © 2021, The Author(s).
Published: 2021

12. Characterization of the Cancer Spectrum in Men with Germline BRCA1 and BRCA2 Pathogenic Variants: Results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA).

Author: Joseph V., Easton D.F., Ejlertsen B., Engel C., Evans D.G., Feliubadalo L., Foretova L., Fostira F., Geczi L., Gerdes A.-M., Glendon G., Godwin A.K., Goldgar D.E., Hahnen E., Hogervorst F.B.L., Hopper J.L., Hulick P.J., Isaacs C., Izquierdo A., James P.A., Janavicius R., Jensen U.B., John E.M., Konstantopoulou I., Kurian A.W., Kwong A., Landucci E., Lesueur F., Loud J.T., Machackova E., Mai P.L., Majidzadeh-A K., Manoukian S., Montagna M., Moserle L., Mulligan A.M., Nathanson K.L., Nevanlinna H., Ngeow Yuen Ye J., Nikitina-Zake L., Offit K., Olah E., Olopade O.I., Osorio A., Papi L., Park S.K., Pedersen I.S., Perez-Segura P., Petersen A.H., Pinto P., Porfirio B., Pujana M.A., Radice P., Rantala J., Rashid M.U., Rosenzweig B., Rossing M., Santamarina M., Schmutzler R.K., Senter L., Simard J., Singer C.F., Solano A.R., Southey M.C., Steele L., Steinsnyder Z., Stoppa-Lyonnet D., Tan Y.Y., Teixeira M.R., Teo S.H., Terry M.B., Thomassen M., Toland A.E., Torres-Esquius S., Tung N., Van Asperen C.J., Vega A., Viel A., Vierstraete J., Wappenschmidt B., Weitzel J.N., Wieme G., Yoon S.-Y., Zorn K.K., Mcguffog L., Parsons M.T., Hamann U., Greene M.H., Kirk J.A., Neuhausen S.L., Rebbeck T.R., Tischkowitz M., Chenevix-Trench G., Antoniou A.C., Friedman E., Ottini L., Silvestri V., Leslie G., Barnes D.R., Agnarsson B.A., Aittomaki K., Alducci E., Andrulis I.L., Barkardottir R.B., Barroso A., Barrowdale D., Benitez J., Bonanni B., Borg A., Buys S.S., Caldes T., Caligo M.A., Capalbo C., Campbell I., Chung W.K., Claes K.B.M., Colonna S.V., Cortesi L., Couch F.J., De La Hoya M., Diez O., Ding Y.C., Domchek S., Joseph V., Easton D.F., Ejlertsen B., Engel C., Evans D.G., Feliubadalo L., Foretova L., Fostira F., Geczi L., Gerdes A.-M., Glendon G., Godwin A.K., Goldgar D.E., Hahnen E., Hogervorst F.B.L., Hopper J.L., Hulick P.J., Isaacs C., Izquierdo A., James P.A., Janavicius R., Jensen U.B., John E.M., Konstantopoulou I., Kurian A.W., Kwong A., Landucci E., Lesueur F., Loud J.T., Machackova E., Mai P.L., Majidzadeh-A K., Manoukian S., Montagna M., Moserle L., Mulligan A.M., Nathanson K.L., Nevanlinna H., Ngeow Yuen Ye J., Nikitina-Zake L., Offit K., Olah E., Olopade O.I., Osorio A., Papi L., Park S.K., Pedersen I.S., Perez-Segura P., Petersen A.H., Pinto P., Porfirio B., Pujana M.A., Radice P., Rantala J., Rashid M.U., Rosenzweig B., Rossing M., Santamarina M., Schmutzler R.K., Senter L., Simard J., Singer C.F., Solano A.R., Southey M.C., Steele L., Steinsnyder Z., Stoppa-Lyonnet D., Tan Y.Y., Teixeira M.R., Teo S.H., Terry M.B., Thomassen M., Toland A.E., Torres-Esquius S., Tung N., Van Asperen C.J., Vega A., Viel A., Vierstraete J., Wappenschmidt B., Weitzel J.N., Wieme G., Yoon S.-Y., Zorn K.K., Mcguffog L., Parsons M.T., Hamann U., Greene M.H., Kirk J.A., Neuhausen S.L., Rebbeck T.R., Tischkowitz M., Chenevix-Trench G., Antoniou A.C., Friedman E., Ottini L., Silvestri V., Leslie G., Barnes D.R., Agnarsson B.A., Aittomaki K., Alducci E., Andrulis I.L., Barkardottir R.B., Barroso A., Barrowdale D., Benitez J., Bonanni B., Borg A., Buys S.S., Caldes T., Caligo M.A., Capalbo C., Campbell I., Chung W.K., Claes K.B.M., Colonna S.V., Cortesi L., Couch F.J., De La Hoya M., Diez O., Ding Y.C., and Domchek S.
Abstract: Importance: The limited data on cancer phenotypes in men with germline BRCA1 and BRCA2 pathogenic variants (PVs) have hampered the development of evidence-based recommendations for early cancer detection and risk reduction in this population. Objective(s): To compare the cancer spectrum and frequencies between male BRCA1 and BRCA2 PV carriers. Design, Setting, and Participant(s): Retrospective cohort study of 6902 men, including 3651 BRCA1 and 3251 BRCA2 PV carriers, older than 18 years recruited from cancer genetics clinics from 1966 to 2017 by 53 study groups in 33 countries worldwide collaborating through the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Clinical data and pathologic characteristics were collected. Main Outcomes and Measures: BRCA1/2 status was the outcome in a logistic regression, and cancer diagnoses were the independent predictors. All odds ratios (ORs) were adjusted for age, country of origin, and calendar year of the first interview. Result(s): Among the 6902 men in the study (median [range] age, 51.6 [18-100] years), 1634 cancers were diagnosed in 1376 men (19.9%), the majority (922 of 1,376 [67%]) being BRCA2 PV carriers. Being affected by any cancer was associated with a higher probability of being a BRCA2, rather than a BRCA1, PV carrier (OR, 3.23; 95% CI, 2.81-3.70; P <.001), as well as developing 2 (OR, 7.97; 95% CI, 5.47-11.60; P <.001) and 3 (OR, 19.60; 95% CI, 4.64-82.89; P <.001) primary tumors. A higher frequency of breast (OR, 5.47; 95% CI, 4.06-7.37; P <.001) and prostate (OR, 1.39; 95% CI, 1.09-1.78; P =.008) cancers was associated with a higher probability of being a BRCA2 PV carrier. Among cancers other than breast and prostate, pancreatic cancer was associated with a higher probability (OR, 3.00; 95% CI, 1.55-5.81; P =.001) and colorectal cancer with a lower probability (OR, 0.47; 95% CI, 0.29-0.78; P =.003) of being a BRCA2 PV carrier. Conclusions and Relevance: Significant differences in the cancer spectrum w
Published: 2021

13. Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores.

Author: Barnes D.R., Silvestri V., Leslie G., McGuffog L., Dennis J., Yang X., Adlard J., Agnarsson B.A., Ahmed M., Aittomaki K., Andrulis I.L., Arason A., Arnold N., Auber B., Azzollini J., Balmana J., Barkardottir R.B., Barrowdale D., Barwell J., Belotti M., Benitez J., Berthet P., Boonen S.E., Borg A., Bozsik A., Brady A., Brennan P., Brewer C., Brunet J., Bucalo A., Buys S.S., Caldes T., Caligo M.A., Campbell I., Cassingham H., Lotte Christensen L., Cini G., Claes K.B.M., Cook J., Coppa A., Cortesi L., Damante G., Darder E., Davidson R., de la Hoya M., De Leeneer K., de Putter R., Del Valle J., Diez O., Chun Ding Y., Domchek S.M., Donaldson A., Eason J., Eeles R., Engel C., Gareth Evans D., Feliubadalo L., Fostira F., Frone M., Frost D., Gallagher D., Gehrig A., Giraud S., Glendon G., Godwin A.K., Goldgar D.E., Greene M.H., Gregory H., Gross E., Hahnen E., Hamann U., Hansen T.V.O., Hanson H., Hentschel J., Horvath J., Izatt L., Izquierdo A., James P.A., Janavicius R., Birk Jensen U., Johannsson O.T., John E.M., Kramer G., Kroeldrup L., Kruse T.A., Lautrup C., Lazaro C., Lesueur F., Lopez-Fernandez A., Mai P.L., Manoukian S., Matrai Z., Matricardi L., Maxwell K.N., Mebirouk N., Meindl A., Montagna M., Monteiro A.N., Morrison P.J., Muranen T.A., Murray A., Nathanson K.L., Neuhausen S.L., Nevanlinna H., Nguyen-Dumont T., Niederacher D., Olah E., Olopade O.I., Palli D., Parsons M.T., Sokilde Pedersen I., Peissel B., Perez-Segura P., Peterlongo P., Petersen A.H., Pinto P., Porteous M.E., Pottinger C., Angel Pujana M., Radice P., Ramser J., Rantala J., Robson M., Rogers M.T., Ronlund K., Rump A., Maria Sanchez de Abajo A., Shah P.D., Sharif S., Side L.E., Singer C.F., Stadler Z., Steele L., Stoppa-Lyonnet D., Sutter C., Yen Tan Y., Teixeira M.R., Teule A., Thull D.L., Tischkowitz M., Toland A.E., Tommasi S., Toss A., Trainer A.H., Tripathi V., Valentini V., van Asperen C.J., Venturelli M., Viel A., Vijai J., Walker L., Wang-Gohrke S., Wappenschmidt B., Whaite A., Zanna I., Offit K., Thomassen M., Couch F.J., Schmutzler R.K., Simard J., Easton D.F., Chenevix-Trench G., Antoniou A.C., Ottini L., Barnes D.R., Silvestri V., Leslie G., McGuffog L., Dennis J., Yang X., Adlard J., Agnarsson B.A., Ahmed M., Aittomaki K., Andrulis I.L., Arason A., Arnold N., Auber B., Azzollini J., Balmana J., Barkardottir R.B., Barrowdale D., Barwell J., Belotti M., Benitez J., Berthet P., Boonen S.E., Borg A., Bozsik A., Brady A., Brennan P., Brewer C., Brunet J., Bucalo A., Buys S.S., Caldes T., Caligo M.A., Campbell I., Cassingham H., Lotte Christensen L., Cini G., Claes K.B.M., Cook J., Coppa A., Cortesi L., Damante G., Darder E., Davidson R., de la Hoya M., De Leeneer K., de Putter R., Del Valle J., Diez O., Chun Ding Y., Domchek S.M., Donaldson A., Eason J., Eeles R., Engel C., Gareth Evans D., Feliubadalo L., Fostira F., Frone M., Frost D., Gallagher D., Gehrig A., Giraud S., Glendon G., Godwin A.K., Goldgar D.E., Greene M.H., Gregory H., Gross E., Hahnen E., Hamann U., Hansen T.V.O., Hanson H., Hentschel J., Horvath J., Izatt L., Izquierdo A., James P.A., Janavicius R., Birk Jensen U., Johannsson O.T., John E.M., Kramer G., Kroeldrup L., Kruse T.A., Lautrup C., Lazaro C., Lesueur F., Lopez-Fernandez A., Mai P.L., Manoukian S., Matrai Z., Matricardi L., Maxwell K.N., Mebirouk N., Meindl A., Montagna M., Monteiro A.N., Morrison P.J., Muranen T.A., Murray A., Nathanson K.L., Neuhausen S.L., Nevanlinna H., Nguyen-Dumont T., Niederacher D., Olah E., Olopade O.I., Palli D., Parsons M.T., Sokilde Pedersen I., Peissel B., Perez-Segura P., Peterlongo P., Petersen A.H., Pinto P., Porteous M.E., Pottinger C., Angel Pujana M., Radice P., Ramser J., Rantala J., Robson M., Rogers M.T., Ronlund K., Rump A., Maria Sanchez de Abajo A., Shah P.D., Sharif S., Side L.E., Singer C.F., Stadler Z., Steele L., Stoppa-Lyonnet D., Sutter C., Yen Tan Y., Teixeira M.R., Teule A., Thull D.L., Tischkowitz M., Toland A.E., Tommasi S., Toss A., Trainer A.H., Tripathi V., Valentini V., van Asperen C.J., Venturelli M., Viel A., Vijai J., Walker L., Wang-Gohrke S., Wappenschmidt B., Whaite A., Zanna I., Offit K., Thomassen M., Couch F.J., Schmutzler R.K., Simard J., Easton D.F., Chenevix-Trench G., Antoniou A.C., and Ottini L.
Abstract: BACKGROUND: Recent population-based female breast cancer and prostate cancer polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers. METHOD(S): 483 BRCA1 and 1,318 BRCA2 European ancestry male carriers were available from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A 147-single nucleotide polymorphism (SNP) prostate cancer PRS (PRSPC) and a 313-SNP breast cancer PRS were evaluated. There were three versions of the breast cancer PRS, optimized to predict overall (PRSBC), estrogen-receptor (ER) negative (PRSER-) or ER-positive (PRSER+) breast cancer risk. RESULT(S): PRSER+ yielded the strongest association with breast cancer risk. The odds ratios (ORs) per PRSER+ standard deviation estimates were 1.40 (95% confidence interval [CI] =1.07-1.83) for BRCA1 and 1.33 (95% CI=1.16-1.52) for BRCA2 carriers. PRSPC was associated with prostate cancer risk for both BRCA1 (OR=1.73, 95% CI=1.28-2.33) and BRCA2 (OR=1.60, 95% CI=1.34-1.91) carriers. The estimated breast cancer ORs were larger after adjusting for female relative breast cancer family history. By age 85years, for BRCA2 carriers, the breast cancer risk varied from 7.7% to 18.4% and prostate cancer risk from 34.1% to 87.6% between the 5th and 95th percentiles of the PRS distributions. CONCLUSION(S): Population-based prostate and female breast cancer PRS are associated with a wide range of absolute breast and prostate cancer risks for male BRCA1 and BRCA2 carriers. These findings warrant further investigation aimed at providing personalized cancer risks for male carriers and to inform clinical management.Copyright © The Author(s) 2021. Published by Oxford University Press.
Published: 2021

14. Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses

Author: Zhan, H.Y., Ahearn, T.U., Lecarpentier, J., Barnes, D., Beesley, J., Qi, G.H., Jiang, X., O'Mara, T.A., Zhao, N., Bolla, M.K., Dunning, A.M., Dennis, J., Wang, Q., Abu Ful, Z., Aittomaki, K., Andrulis, I.L., Anton-Culver, H., Arndt, V., Aronson, K.J., Arun, B.K., Auer, P.L., Azzollini, J., Barrowdale, D., Becher, H., Beckmann, M.W., Behrens, S., Benitez, J., Bermisheva, M., Bialkowska, K., Blanco, A., Blomqvist, C., Bogdanova, N.V., Bojesen, S.E., Bonanni, B., Bondavalli, D., Borg, A., Brauch, H., Brenner, H., Briceno, I., Broeks, A., Brucker, S.Y., Bruning, T., Burwinkel, B., Buys, S.S., Byers, H., Caldes, T., Caligo, M.A., Calvello, M., Campa, D., Castelao, J.E., Chang-Claude, J., Chanock, S.J., Christiaens, M., Christiansen, H., Chung, W.K., Claes, K.B.M., Clarke, C.L., Cornelissen, S., Couch, F.J., Cox, A., Cross, S.S., Czene, K., Daly, M.B., Devilee, P., Diez, O., Domchek, S.M., Dork, T., Dwek, M., Eccles, D.M., Ekici, A.B., Evans, D.G., Fasching, P.A., Figueroa, J., Foretova, L., Fostira, F., Friedman, E., Frost, D., Gago-Dominguez, M., Gapstur, S.M., Garber, J., Garcia-Saenz, J.A., Gaudet, M.M., Gayther, S.A., Giles, G.G., Godwin, A.K., Goldberg, M.S., Goldgar, D.E., Gonzalez-Neira, A., Greene, M.H., Gronwald, J., Guenel, P., Haberle, L., Hahnen, E., Haiman, C.A., Hake, C.R., Hall, P., Hamann, U., Harkness, E.F., Heemskerk-Gerritsen, B.A.M., Hillemanns, P., Hogervorst, F.B.L., Holleczek, B., Hollestelle, A., Hooning, M.J., Hoover, R.N., Hopper, J.L., Howell, A., Huebner, H., Hulick, P.J., Imyanitov, E.N., Isaacs, C., Izatt, L., Jager, A., Jakimovska, M., Jakubowska, A., James, P., Janavicius, R., Janni, W., John, E.M., Jones, M.E., Jung, A., Kaaks, R., Kapoor, P.M., Karlan, B.Y., Keeman, R., Khan, S., Khusnutdinova, E., Kitahara, C.M., Ko, Y.D., Konstantopoulou, I., Koppert, L.B., Koutros, S., Kristensen, V.N., Laenkholm, A.V., Lambrechts, D., Larsson, S.C., Laurent-Puig, P., Lazaro, C., Lazarova, E., Lejbkowicz, F., Leslie, G., Lesueur, F., Lindblom, A., Lissowska, J., W.Y. lo, Loud, J.T., Lubinski, J., Lukomska, A., MacInnis, R.J., Mannermaa, A., Manoochehri, M., Manoukian, S., Margolin, S., Martinez, M.E., Matricardi, L., McGuffog, L., McLean, C., Mebirouk, N., Meindl, A., Menon, U., Miller, A., Mingazheva, E., Montagna, M., Mulligan, A.M., Mulot, C., Muranen, T.A., Nathanson, K.L., Neuhausen, S.L., Nevanlinna, H., Neven, P., Newman, W.G., Nielsens, F.C., Nikitina-Zake, L., Nodora, J., Offit, K., Olah, E., Olopade, O.I., Olsson, H., Orr, N., Papi, L., Papp, J., Park-Simon, T.W., Parsons, M.T., Peissel, B., Peixoto, A., Peshkin, B., Peterlongo, P., Peto, J., Phillips, K.A., Piedmonte, M., Plaseska-Karanfilska, D., Prajzendanc, K., Prentice, R., Prokofyeva, D., Rack, B., Radice, P., Ramus, S.J., Rantala, J., Rashid, M.U., Rennert, G., Rennert, H.S., Risch, H.A., Romero, A., Rookus, M.A., Rubner, M., Rudiger, T., Saloustros, E., Sampson, S., Sandler, D.P., Sawyer, E.J., Scheuner, M.T., Schmutzler, R.K., Schneeweiss, A., Schoemaker, M.J., Schottker, B., Schurmann, P., Senter, L., Sharma, P., Sherman, M.E., Shu, X.O., Singer, C.F., Smichkoska, S., Soucy, P., Southey, M.C., Spinelli, J.J., Stone, J., Stoppa-Lyonnet, D., Swerdlow, A.J., Szabo, C.I., Tamimi, R.M., Tapper, W.J., Taylor, J.A., Teixeira, M.R., Terry, M., Thomassen, M., Thull, D.L., Tischkowitz, M., Toland, A.E., Tollenaar, R.A.E.M., Tomlinson, I., Torres, D., Troester, M.A., Truong, T., Tung, N., Untch, M., Vachon, C.M., Ouweland, A.M.W. van den, Kolk, L.E. van der, Veen, E.M. van, vanRensburg, E.J., Vega, A., Wappenschmidt, B., Weinberg, C.R., Weitzel, J.N., Wildiers, H., Winqvist, R., Wolk, A., Yang, X.H.R., Yannoukakos, D., Zheng, W., Zorn, K.K., Milne, R.L., Kraft, P., Simard, J., Pharoah, P.D.P., Michailidou, K., Antoniou, A.C., Schmidt, M.K., Chenevix-Trench, G., Easton, D.F., Chatterjee, N., Garcia-Closas, M., kConFab Investigators, ABCTB Investigators, EMBRACE Study, and GEMO Study Collaborators
Abstract: Genome-wide analysis identifies 32 loci associated with breast cancer susceptibility, accounting for estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade.Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype(1-3). To identify novel loci, we performed a genome-wide association study including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. We identified 32 novel susceptibility loci (P < 5.0 x 10(-8)), 15 of which showed evidence for associations with at least one tumor feature (false discovery rate < 0.05). Five loci showed associations (P < 0.05) in opposite directions between luminal and non-luminal subtypes. In silico analyses showed that these five loci contained cell-specific enhancers that differed between normal luminal and basal mammary cells. The genetic correlations between five intrinsic-like subtypes ranged from 0.35 to 0.80. The proportion of genome-wide chip heritability explained by all known susceptibility loci was 54.2% for luminal A-like disease and 37.6% for triple-negative disease. The odds ratios of polygenic risk scores, which included 330 variants, for the highest 1% of quantiles compared with middle quantiles were 5.63 and 3.02 for luminal A-like and triple-negative disease, respectively. These findings provide an improved understanding of genetic predisposition to breast cancer subtypes and will inform the development of subtype-specific polygenic risk scores.
Published: 2020

15. Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes

Author: Fachal, L., Aschard, H., Beesley, J., Barnes, D.R., Allen, J., Kar, S., Pooley, K.A., Dennis, J., Michailidou, K., Turman, C., Soucy, P., Lemaçon, A., Lush, M., Tyrer, J.P., Ghoussaini, M., Marjaneh, M.M., Jiang, X., Agata, S., Aittomäki, K., Alonso, M.R., Andrulis, I.L., Anton-Culver, H., Antonenkova, N.N., Arason, A., Arndt, V., Aronson, K.J., Arun, B.K., Auber, B., Auer, P.L., Azzollini, J., Balmaña, J., Barkardottir, R.B., Barrowdale, D., Beeghly-Fadiel, A., Benitez, J., Bermisheva, M., Białkowska, K., Blanco, A.M., Blomqvist, C., Blot, W., Bogdanova, N.V., Bojesen, S.E., Bolla, M.K., Bonanni, B., Borg, A., Bosse, K., Brauch, H., Brenner, H., Briceno, I., Brock, I.W., Brooks-Wilson, A., Brüning, T., Burwinkel, B., Buys, S.S., Cai, Q., Caldés, T., Caligo, M.A., Camp, N.J., Campbell, I., Canzian, F., Carroll, J.S., Carter, B.D., Castelao, J.E., Chiquette, J., Christiansen, H., Chung, W.K., Claes, K.B.M., Clarke, C.L., Mari, V., Berthet, P., Castera, L., Vaur, D., Lallaoui, H., Bignon, Y.-J., Uhrhammer, N., Bonadona, V., Lasset, C., Révillion, F., Vennin, P., Muller, D., Gomes, D.M., Ingster, O., Coupier, I., Pujol, P., Collonge-Rame, M.-A., Mortemousque, I., Bera, O., Rose, M., Baurand, A., Bertolone, G., Faivre, L., Dreyfus, H., Leroux, D., Venat-Bouvet, L., Bézieau, S., Delnatte, C., Chiesa, J., Gilbert-Dussardier, B., Gesta, P., Prieur, F.P., Bronner, M., Sokolowska, J., Coulet, F., Boutry-Kryza, N., Calender, A., Giraud, S., Leone, M., Fert-Ferrer, S., Stoppa-Lyonnet, D., Jiao, Y., Lesueur, F.L., Mebirouk, N., Barouk-Simonet, E., Bubien, V., Longy, M., Sevenet, N., Gladieff, L., Toulas, C., Reimineras, A., Sobol, H., Paillerets, B.B.-D., Cabaret, O., Caron, O., Guillaud-Bataille, M., Rouleau, E., Belotti, M., Buecher, B., Caputo, S., Colas, C., Pauw, A.D., Fourme, E., Gauthier-Villars, M., Golmard, L., Moncoutier, V., Saule, C., Donaldson, A., Murray, A., Brady, A., Brewer, C., Pottinger, C., Miller, C., Gallagher, D., Gregory, H., Cook, J., Eason, J., Adlard, J., Barwell, J., Ong, K.-R., Snape, K., Walker, L., Izatt, L., Side, L., Tischkowitz, M., Rogers, M.T., Porteous, M.E., Ahmed, M., Morrison, P.J., Brennan, P., Eeles, R., Davidson, R., Collée, M., Cornelissen, S., Couch, F.J., Cox, A., Cross, S.S., Cybulski, C., Czene, K., Daly, M.B., de la Hoya, M., Devilee, P., Diez, O., Ding, Y.C., Dite, G.S., Domchek, S.M., Dörk, T., dos-Santos-Silva, I., Droit, A., Dubois, S., Dumont, M., Duran, M., Durcan, L., Dwek, M., Eccles, D.M., Engel, C., Eriksson, M., Evans, D.G., Fasching, P.A., Fletcher, O., Floris, G., Flyger, H., Foretova, L., Foulkes, W.D., Friedman, E., Fritschi, L., Frost, D., Gabrielson, M., Gago-Dominguez, M., Gambino, G., Ganz, P.A., Gapstur, S.M., Garber, J., García-Sáenz, J.A., Gaudet, M.M., Georgoulias, V., Giles, G., Glendon, G., Godwin, A.K., Goldberg, M.S., Goldgar, D.E., González-Neira, A., Tibiletti, M.G., Greene, M.H., Grip, M., Gronwald, J., Grundy, A., Guénel, P., Hahnen, E., Haiman, C.A., Håkansson, N., Hall, P., Hamann, U., Harrington, P.A., Hartikainen, J.M., Hartman, M., He, W., Healey, C.S., Heemskerk-Gerritsen, B.A.M., Heyworth, J., Hillemanns, P., Hogervorst, F.B.L., Hollestelle, A., Hooning, M., Hopper, J., Howell, A., Huang, G., Hulick, P.J., Imyanitov, E.N., Sexton, A., Christian, A., Trainer, A., Spigelman, A., Fellows, A., Shelling, A., Fazio, A.D., Blackburn, A., Crook, A., Meiser, B., Patterson, B., Clarke, C., Saunders, C., Hunt, C., Scott, C., Amor, D., Marsh, D., Edkins, E., Salisbury, E., Haan, E., Neidermayr, E., Macrea, F., Farshid, G., Lindeman, G., Chenevix-Trench, G., Mann, G., Gill, G., Thorne, H., Hickie, I., Winship, I., Flanagan, J., Kollias, J., Visvader, J., Stone, J., Taylor, J., Burke, J., Saunus, J., Forbes, J., Kirk, J., French, J., Tucker, K., Wu, K., Phillips, K., Lipton, L., Andrews, L., Lobb, L., Kentwell, M., Spurdle, M., Cummings, M., Gleeson, M., Harris, M., Jenkins, M., Young, M.A., Delatycki, M., Wallis, M., Burgess, M., Price, M., Brown, M., Southey, M., Bogwitz, M., Field, M., Friedlander, M., Gattas, M., Saleh, M., Hayward, N., Pachter, N., Cohen, P., Duijf, P., James, P., Simpson, P., Fong, P., Butow, P., Williams, R., Kefford, R., Scott, R., Milne, R.L., Balleine, R., Dawson, S.–J., Lok, S., O’Connell, S., Greening, S., Nightingale, S., Edwards, S., Fox, S., McLachlan, S.-A., Lakhani, S., Antill, Y., Aalfs, C., Meijers-Heijboer, H., van Engelen, K., Gille, H., Boere, I., van Deurzen, C., Obdeijn, I.-M., van den Ouweland, A., Seynaeve, C., Siesling, S., Verloop, J., van Asperen, C.J., van Cronenburg, T., Blok, R., de Boer, M., Garcia, E.G., Adank, M., Hogervorst, F., Jenner, D., van Leeuwen, F., Rookus, M., Russell, N., Schmidt, M., van den Belt-Dusebout, S., Kets, C., Mensenkamp, A., de Bock, T., van der Hout, A., Mourits, M., Oosterwijk, J., Ausems, M., Koudijs, M., Baxter, R., Yip, D., Carpenter, J., Davis, A., Pathmanathan, N., Graham, D., Sachchithananthan, M., Isaacs, C., Iwasaki, M., Jager, A., Jakimovska, M., Jakubowska, A., James, P.A., Janavicius, R., Jankowitz, R.C., John, E.M., Johnson, N., Jones, M.E., Jukkola-Vuorinen, A., Jung, A., Kaaks, R., Kang, D., Kapoor, P.M., Karlan, B.Y., Keeman, R., Kerin, M.J., Khusnutdinova, E., Kiiski, J.I., Kitahara, C.M., Ko, Y.-D., Konstantopoulou, I., Kosma, V.-M., Koutros, S., Kubelka-Sabit, K., Kwong, A., Kyriacou, K., Laitman, Y., Lambrechts, D., Lee, E., Leslie, G., Lester, J., Lesueur, F., Lindblom, A., Lo, W.-Y., Long, J., Lophatananon, A., Loud, J.T., Lubiński, J., MacInnis, R.J., Maishman, T., Makalic, E., Mannermaa, A., Manoochehri, M., Manoukian, S., Margolin, S., Martinez, M.E., Matsuo, K., Maurer, T., Mavroudis, D., Mayes, R., McGuffog, L., McLean, C., Meindl, A., Miller, A., Miller, N., Montagna, M., Moreno, F., Muir, K., Mulligan, A.M., Muñoz-Garzon, V.M., Muranen, T.A., Narod, S.A., Nassir, R., Nathanson, K.L., Neuhausen, S.L., Nevanlinna, H., Neven, P., Nielsen, F.C., Nikitina-Zake, L., Norman, A., Offit, K., Olah, E., Olopade, O.I., Olsson, H., Orr, N., Osorio, A., Pankratz, V.S., Papp, J., Park, S.K., Park-Simon, T.-W., Parsons, M.T., Paul, J., Pedersen, I.S., Peissel, B., Peshkin, B., Peterlongo, P., Peto, J., Plaseska-Karanfilska, D., Prajzendanc, K., Prentice, R., Presneau, N., Prokofyeva, D., Pujana, M.A., Pylkäs, K., Radice, P., Ramus, S.J., Rantala, J., Rau-Murthy, R., Rennert, G., Risch, H.A., Robson, M., Romero, A., Rossing, M., Saloustros, E., Sánchez-Herrero, E., Sandler, D.P., Santamariña, M., Sawyer, E.J., Scheuner, M.T., Schmidt, D.F., Schmutzler, R.K., Schneeweiss, A., Schoemaker, M.J., Schöttker, B., Schürmann, P., Scott, R.J., Senter, L., Seynaeve, C.M., Shah, M., Sharma, P., Shen, C.-Y., Shu, X.-O., Singer, C.F., Slavin, T.P., Smichkoska, S., Southey, M.C., Spinelli, J.J., Spurdle, A.B., Sutter, C., Swerdlow, A.J., Tamimi, R.M., Tan, Y.Y., Tapper, W.J., Taylor, J.A., Teixeira, M.R., Tengström, M., Teo, S.H., Terry, M.B., Teulé, A., Thomassen, M., Thull, D.L., Toland, A.E., Tollenaar, R.A.E.M., Tomlinson, I., Torres, D., Torres-Mejía, G., Troester, M.A., Truong, T., Tung, N., Tzardi, M., Ulmer, H.-U., Vachon, C.M., van der Kolk, L.E., van Rensburg, E.J., Vega, A., Viel, A., Vijai, J., Vogel, M.J., Wang, Q., Wappenschmidt, B., Weinberg, C.R., Weitzel, J.N., Wendt, C., Wildiers, H., Winqvist, R., Wolk, A., Wu, A.H., Yannoukakos, D., Zhang, Y., Zheng, W., Hunter, D., Pharoah, P.D.P., Chang-Claude, J., García-Closas, M., Schmidt, M.K., Kristensen, V.N., French, J.D., Edwards, S.L., Antoniou, A.C., Simard, J., Easton, D.F., Kraft, P., Dunning, A.M., Collaborators, GEMO Study, Collaborators, EMBRACE, Investigators, KConFab, Investigators, HEBON, Investigators, ABCTB, Fachal, Laura, Aschard, Hugues, Beesley, Jonathan, Barnes, Daniel R, Duijf, Pascal, Dunning, Alison M, GEMO Study Collaborators, EMBRACE Collaborators, KConFab Investigators, HEBON Investigators, ABCTB Investigators, MUMC+: MA Medische Oncologie (9), RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Klinische Genetica, MUMC+: DA KG Polikliniek (9), RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: DA KG Lab Centraal Lab (9), European Commission, Government of Canada, Canadian Institutes of Health Research, National Institutes of Health (US), Cancer Research UK, Département de Biologie Computationnelle - Department of Computational Biology, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), QIMR Berghofer Medical Research Institute, University of Cambridge [UK] (CAM), NSCAD, University of Cyprus [Nicosia], Harvard T.H. Chan School of Public Health, This work was supported by the European Union’s Horizon 2020 Research and Innovation Programme under Marie Sklodowska-Curie grant agreement number 656144. Genotyping of the OncoArray was principally funded from three sources: the PERSPECTIVE project (funded by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research, the ‘Ministère de l’Économie de la Science et de l’Innovation du Québec’ (through Genome Québec) and the Quebec Breast Cancer Foundation), the NCI Genetic Associations and Mechanisms in Oncology (GAME-ON) initiative and the Discovery, Biology and Risk of Inherited Variants in Breast Cancer (DRIVE) project (NIH grants U19 CA148065 and X01HG007492), and Cancer Research UK (C1287/A10118, C8197/A16565 and C1287/A16563). BCAC is funded by Cancer Research UK (C1287/A16563), by the European Community’s Seventh Framework Programme under grant agreement 223175 (HEALTH-F2-2009-223175) (COGS) and by the European Union’s Horizon 2020 Research and Innovation Programme under grant agreements 633784 (B-CAST) and 634935 (BRIDGES). Genotyping of the iCOGS array was funded by the European Union (HEALTH-F2-2009-223175), Cancer Research UK (C1287/A10710), the Canadian Institutes of Health Research for the ‘CIHR Team in Familial Risks of Breast Cancer’ program, and the Ministry of Economic Development, Innovation and Export Trade of Quebec (grant PSR-SIIRI-701). Combining of the GWAS data was supported in part by NIH Cancer Post-Cancer GWAS initiative grant U19 CA 148065 (DRIVE, part of the GAME-ON initiative). For a full description of funding and acknowledgments, see the Supplementary Note., We thank all of the individuals who took part in these studies, as well as all of the researchers, clinicians, technicians and administrative staff who enabled this work to be carried out, European Project: 656144,H2020,H2020-MSCA-IF-2014,RADIOGENFF(2016), European Project: 223175,EC:FP7:HEALTH,FP7-HEALTH-2007-B,COGS(2009), European Project: 633784,H2020,H2020-PHC-2014-two-stage,B-CAST(2015), European Project: 634935,H2020,H2020-PHC-2014-two-stage,BRIDGES(2015), Clinical Genetics, Medical Oncology, Pathology, Radiology & Nuclear Medicine, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), University of Cyprus [Nicosia] (UCY), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Life Course Epidemiology (LCE), Targeted Gynaecologic Oncology (TARGON), Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), Aschard, Hugues [0000-0002-7554-6783], Barnes, Daniel R [0000-0002-3781-7570], Dennis, Joe [0000-0003-4591-1214], Michailidou, Kyriaki [0000-0001-7065-1237], Lemaçon, Audrey [0000-0002-1817-7029], Andrulis, Irene L [0000-0002-4226-6435], Arason, Adalgeir [0000-0003-0480-886X], Arndt, Volker [0000-0001-9320-8684], Auber, Bernd [0000-0003-1880-291X], Azzollini, Jacopo [0000-0002-9364-9778], Bojesen, Stig E [0000-0002-4061-4133], Bonanni, Bernardo [0000-0003-3589-2128], Brauch, Hiltrud [0000-0001-7531-2736], Campbell, Ian [0000-0002-7773-4155], Carroll, Jason S [0000-0003-3643-0080], Claes, Kathleen BM [0000-0003-0841-7372], Collée, J Margriet [0000-0002-9272-9346], Devilee, Peter [0000-0002-8023-2009], Dörk, Thilo [0000-0002-9458-0282], Dwek, Miriam [0000-0001-7184-2932], Fletcher, Olivia [0000-0001-9387-7116], Floris, Giuseppe [0000-0003-2391-5425], Foulkes, William D [0000-0001-7427-4651], García-Sáenz, José A [0000-0001-6880-0301], Greene, Mark H [0000-0003-1852-9239], Guénel, Pascal [0000-0002-8359-518X], Heemskerk-Gerritsen, Bernadette AM [0000-0002-9724-6693], Hollestelle, Antoinette [0000-0003-1166-1966], Hulick, Peter J [0000-0001-8397-4078], Jakimovska, Milena [0000-0002-1506-0669], Jakubowska, Anna [0000-0002-5650-0501], James, Paul A [0000-0002-4361-4657], Jones, Michael E [0000-0001-7479-3451], Kapoor, Pooja Middha [0000-0001-5503-8215], Keeman, Renske [0000-0002-5452-9933], Konstantopoulou, Irene [0000-0002-0470-0309], Leslie, Goska [0000-0001-5756-6222], Lesueur, Fabienne [0000-0001-7404-4549], Matsuo, Keitaro [0000-0003-1761-6314], McLean, Catriona [0000-0002-0302-5727], Miller, Austin [0000-0001-9739-8462], Muir, Kenneth [0000-0001-6429-988X], Muranen, Taru A [0000-0002-5895-1808], Nathanson, Katherine L [0000-0002-6740-0901], Nevanlinna, Heli [0000-0002-0916-2976], Olopade, Olufunmilayo I [0000-0002-9936-1599], Orr, Nick [0000-0003-2866-942X], Pankratz, V Shane [0000-0002-3742-040X], Parsons, Michael T [0000-0003-3242-8477], Paul, James [0000-0001-7367-5816], Peshkin, Beth [0000-0002-2997-4701], Peterlongo, Paolo [0000-0001-6951-6855], Peto, Julian [0000-0002-1685-8912], Plaseska-Karanfilska, Dijana [0000-0001-8877-2416], Pylkäs, Katri [0000-0002-2449-0521], Radice, Paolo [0000-0001-6298-4111], Rennert, Gad [0000-0002-8512-068X], Robson, Mark [0000-0002-3109-1692], Romero, Atocha [0000-0002-1634-7397], Saloustros, Emmanouil [0000-0002-0485-0120], Scott, Christopher [0000-0003-1340-0647], Scott, Rodney J [0000-0001-7724-3404], Spurdle, Amanda B [0000-0003-1337-7897], Stone, Jennifer [0000-0001-5077-0124], Sutter, Christian [0000-0003-4051-5888], Tan, Yen Yen [0000-0003-1063-5352], Teixeira, Manuel R [0000-0002-4896-5982], Toland, Amanda E [0000-0002-0271-1792], Tomlinson, Ian [0000-0003-3037-1470], Viel, Alessandra [0000-0003-2804-0840], Vijai, Joseph [0000-0002-7933-151X], Wolk, Alicja [0000-0001-7387-6845], Yannoukakos, Drakoulis [0000-0001-7509-3510], Pharoah, Paul DP [0000-0001-8494-732X], Schmidt, Marjanka K [0000-0002-2228-429X], Milne, Roger L [0000-0001-5764-7268], Edwards, Stacey L [0000-0001-7428-4139], Simard, Jacques [0000-0001-6906-3390], Easton, Douglas F [0000-0003-2444-3247], Kraft, Peter [0000-0002-4472-8103], Dunning, Alison M [0000-0001-6651-7166], Apollo - University of Cambridge Repository, Academic Medical Center, ARD - Amsterdam Reproduction and Development, Human genetics, CCA - Cancer biology and immunology, Molecular cell biology and Immunology, Medicum, Kristiina Aittomäki / Principal Investigator, HUSLAB, Department of Medical and Clinical Genetics, University of Helsinki, HUS Comprehensive Cancer Center, Department of Oncology, Clinicum, Doctoral Programme in Clinical Research, Staff Services, INDIVIDRUG - Individualized Drug Therapy, HUS Gynecology and Obstetrics, and Department of Obstetrics and Gynecology
Subjects: CHROMATIN, Linkage disequilibrium, Genome-wide association study, Regulatory Sequences, Nucleic Acid, Genome-wide association studies, Linkage Disequilibrium, Basic medicine, 0302 clinical medicine, Breast cancer, MESH: Risk Factors, Risk Factors, COMPREHENSIVE MOLECULAR PORTRAITS, 11 Medical and Health Sciences, HEBON Investigators, Genetics & Heredity, 0303 health sciences, [STAT.AP]Statistics [stat]/Applications [stat.AP], PROTEIN FUNCTION, Tumor, breast tumor, MESH: Polymorphism, Single Nucleotide, 1184 Genetics, developmental biology, physiology, MESH: Genetic Predisposition to Disease, apoptosis, Chromosome Mapping, Single Nucleotide, 3. Good health, MESH: Linkage Disequilibrium, Female, MESH: Biomarkers, Tumor, Biomarkers, Tumor/genetics, [STAT.ME]Statistics [stat]/Methodology [stat.ME], Life Sciences & Biomedicine, SUSCEPTIBILITY LOCI, MESH: Bayes Theorem, Quantitative Trait Loci, ABCTB Investigators, INTEGRATIVE ANALYSIS, Breast Neoplasms, Computational biology, Biology, Quantitative trait locus, Breast Neoplasms/genetics, Polymorphism, Single Nucleotide, Article, ENHANCER, GEMO Study Collaborators, 03 medical and health sciences, breast cancer, SDG 3 - Good Health and Well-being, REVEALS, Genetics, Biomarkers, Tumor, MESH: Regulatory Sequences, Nucleic Acid, Humans, Genetic Predisposition to Disease, Polymorphism, GENOME-WIDE ASSOCIATION, FUNCTIONAL VARIANTS, EMBRACE Collaborators, Gene, 030304 developmental biology, Genetic association, Bayes Theorem, Genome-Wide Association Study, MESH: Humans, Science & Technology, Nucleic Acid, gene mapping, 06 Biological Sciences, MESH: Quantitative Trait Loci, DNA binding site, ESTROGEN-RECEPTOR, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Clinical medicine, Expression quantitative trait loci, MESH: Genome-Wide Association Study, Human genome, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, KConFab Investigators, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], MESH: Chromosome Mapping, Chromosome Mapping/methods, Regulatory Sequences, MESH: Female, Biomarkers, 030217 neurology & neurosurgery, MESH: Breast Neoplasms, Developmental Biology
Abstract: Genome-wide association studies have identified breast cancer risk variants in over 150 genomic regions, but the mechanisms underlying risk remain largely unknown. These regions were explored by combining association analysis with in silico genomic feature annotations. We defined 205 independent risk-associated signals with the set of credible causal variants in each one. In parallel, we used a Bayesian approach (PAINTOR) that combines genetic association, linkage disequilibrium and enriched genomic features to determine variants with high posterior probabilities of being causal. Potentially causal variants were significantly over-represented in active gene regulatory regions and transcription factor binding sites. We applied our INQUSIT pipeline for prioritizing genes as targets of those potentially causal variants, using gene expression (expression quantitative trait loci), chromatin interaction and functional annotations. Known cancer drivers, transcription factors and genes in the developmental, apoptosis, immune system and DNA integrity checkpoint gene ontology pathways were over-represented among the highest-confidence target genes., This work was supported by the European Union’s Horizon 2020 Research and Innovation Programme under Marie Sklodowska-Curie grant agreement number 656144. Genotyping of the OncoArray was principally funded from three sources: the PERSPECTIVE project (funded by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research, the ‘Ministère de l’Économie de la Science et de l’Innovation du Québec’ (through Genome Québec) and the Quebec Breast Cancer Foundation); the NCI Genetic Associations and Mechanisms in Oncology (GAME-ON) initiative and the Discovery, Biology and Risk of Inherited Variants in Breast Cancer (DRIVE) project (NIH grants U19 CA148065 and X01HG007492); and Cancer Research UK (C1287/A10118, C8197/A16565 and C1287/A16563). BCAC is funded by Cancer Research UK (C1287/A16563), by the European Community’s Seventh Framework Programme under grant agreement 223175 (HEALTH-F2-2009-223175) (COGS) and by the European Union’s Horizon 2020 Research and Innovation Programme under grant agreements 633784 (B-CAST) and 634935 (BRIDGES). Genotyping of the iCOGS array was funded by the European Union (HEALTH-F2-2009-223175), Cancer Research UK (C1287/A10710), the Canadian Institutes of Health Research for the ‘CIHR Team in Familial Risks of Breast Cancer’ program, and the Ministry of Economic Development, Innovation and Export Trade of Quebec (grant PSR-SIIRI-701). Combining of the GWAS data was supported in part by NIH Cancer Post-Cancer GWAS initiative grant U19 CA 148065 (DRIVE; part of the GAME-ON initiative).
Published: 2020

16. Association of Genomic Domains in BRCA1 and BRCA2 with Prostate Cancer Risk and Aggressiveness

Author: Patel, V.L., Busch, E.L., Friebel, T.M., Cronin, A., Leslie, G., McGuffog, L., Adlard, J., Agata, S., Agnarsson, B.A., Ahmed, M., Aittomaki, K., Alducci, E., Andrulis, I.L., Arason, A., Arnold, N., Artioli, G., Arver, B., Auber, B., Azzollini, J., Balmana, J., Barkardottir, R.B., Barnes, D.R., Barroso, A., Barrowdale, D., Belotti, M., Benitez, J., Bertelsen, B., Blok, M.J., Bodrogi, I., Bonadona, V., Bonanni, B., Bondavalli, D., Boonen, S.E., Borde, J., Borg, A., Bradbury, A.R., Brady, A., Brewer, C., Brunet, J., Buecher, B., Buys, S.S., Cabezas-Camarero, S., Caldes, T., Caliebe, A., Caligo, M.A., Calvello, M., Campbell, I.G., Carnevali, I., Carrasco, E., Chan, T.L., Chu, A.T.W., Chung, W.K., Claes, K.B.M., Cook, J., Cortesi, L., Couch, F.J., Daly, M.B., Damante, G., Darder, E., Davidson, R., Hoya, M. de la, Puppa, L.D., Dennis, J., Diez, O., Ding, Y.C., Ditsch, N., Domchek, S.M., Donaldson, A., Dworniczak, B., Easton, D.F., Eccles, D.M., Eeles, R.A., Ehrencrona, H., Ejlertsen, B., Engel, C., Evans, D.G., Faivre, L., Faust, U., Feliubadalo, L., Foretova, L., Fostira, F., Fountzilas, G., Frost, D., Garcia-Barberan, V., Garre, P., Gauthier-Villars, M., Geczi, L., Gehrig, A., Gerdes, A.M., Gesta, P., Giannini, G., Glendon, G., Godwin, A.K., Goldgar, D.E., Greene, M.H., Gutierrez-Barrera, A.M., Hahnen, E., Hamann, U., Mensenkamp, A.R., Nielsen, H., Rebbeck, T.R., Patel, V.L., Busch, E.L., Friebel, T.M., Cronin, A., Leslie, G., McGuffog, L., Adlard, J., Agata, S., Agnarsson, B.A., Ahmed, M., Aittomaki, K., Alducci, E., Andrulis, I.L., Arason, A., Arnold, N., Artioli, G., Arver, B., Auber, B., Azzollini, J., Balmana, J., Barkardottir, R.B., Barnes, D.R., Barroso, A., Barrowdale, D., Belotti, M., Benitez, J., Bertelsen, B., Blok, M.J., Bodrogi, I., Bonadona, V., Bonanni, B., Bondavalli, D., Boonen, S.E., Borde, J., Borg, A., Bradbury, A.R., Brady, A., Brewer, C., Brunet, J., Buecher, B., Buys, S.S., Cabezas-Camarero, S., Caldes, T., Caliebe, A., Caligo, M.A., Calvello, M., Campbell, I.G., Carnevali, I., Carrasco, E., Chan, T.L., Chu, A.T.W., Chung, W.K., Claes, K.B.M., Cook, J., Cortesi, L., Couch, F.J., Daly, M.B., Damante, G., Darder, E., Davidson, R., Hoya, M. de la, Puppa, L.D., Dennis, J., Diez, O., Ding, Y.C., Ditsch, N., Domchek, S.M., Donaldson, A., Dworniczak, B., Easton, D.F., Eccles, D.M., Eeles, R.A., Ehrencrona, H., Ejlertsen, B., Engel, C., Evans, D.G., Faivre, L., Faust, U., Feliubadalo, L., Foretova, L., Fostira, F., Fountzilas, G., Frost, D., Garcia-Barberan, V., Garre, P., Gauthier-Villars, M., Geczi, L., Gehrig, A., Gerdes, A.M., Gesta, P., Giannini, G., Glendon, G., Godwin, A.K., Goldgar, D.E., Greene, M.H., Gutierrez-Barrera, A.M., Hahnen, E., Hamann, U., Mensenkamp, A.R., Nielsen, H., and Rebbeck, T.R.
Abstract: Contains fulltext : 218251.pdf (Publisher’s version ) (Closed access), Pathogenic sequence variants (PSV) in BRCA1 or BRCA2 (BRCA1/2) are associated with increased risk and severity of prostate cancer. We evaluated whether PSVs in BRCA1/2 were associated with risk of overall prostate cancer or high grade (Gleason 8+) prostate cancer using an international sample of 65 BRCA1 and 171 BRCA2 male PSV carriers with prostate cancer, and 3,388 BRCA1 and 2,880 BRCA2 male PSV carriers without prostate cancer. PSVs in the 3' region of BRCA2 (c.7914+) were significantly associated with elevated risk of prostate cancer compared with reference bin c.1001-c.7913 [HR = 1.78; 95% confidence interval (CI), 1.25-2.52; P = 0.001], as well as elevated risk of Gleason 8+ prostate cancer (HR = 3.11; 95% CI, 1.63-5.95; P = 0.001). c.756-c.1000 was also associated with elevated prostate cancer risk (HR = 2.83; 95% CI, 1.71-4.68; P = 0.00004) and elevated risk of Gleason 8+ prostate cancer (HR = 4.95; 95% CI, 2.12-11.54; P = 0.0002). No genotype-phenotype associations were detected for PSVs in BRCA1. These results demonstrate that specific BRCA2 PSVs may be associated with elevated risk of developing aggressive prostate cancer. SIGNIFICANCE: Aggressive prostate cancer risk in BRCA2 mutation carriers may vary according to the specific BRCA2 mutation inherited by the at-risk individual.
Published: 2020

17. Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants

Author: Barnes, D.R., Rookus, Matti A., McGuffog, L., Leslie, G., Mooij, T.M., Dennis, J., Mavaddat, N., Adlard, J., Ahmed, M., Aittomäki, K., Andrieu, N., Andrulis, I.L., Arnold, N., Arun, B.K., Azzollini, J., Balmaña, J., Barkardottir, R.B., Barrowdale, D., Benitez, J., Berthet, P., Białkowska, K., Blanco, A.M., Blok, M.J., Bonanni, B., Boonen, S.E., Borg, Å., Bozsik, A., Bradbury, A.R., Brennan, P., Brewer, C., Brunet, J., Buys, S.S., Caldés, T., Caligo, M.A., Campbell, I., Christensen, L.L., Chung, W.K., Claes, K.B.M., Colas, C., Collonge-Rame, M.A., Cook, J., Daly, M.B., Davidson, R., Hoya, M. de la, Putter, R. de, Delnatte, C., Devilee, P., Diez, O., Ding, Y.C., Domchek, S.M., Dorfling, C.M., Dumont, M., Eeles, R., Ejlertsen, B., Engel, C., Evans, D.G., Faivre, L., Foretova, L., Fostira, F., Friedlander, M., Friedman, E., Frost, D., Ganz, P.A., Garber, J., Gehrig, A., Gerdes, A.M., Gesta, P., Giraud, S., Glendon, G., Godwin, A.K., Goldgar, D.E., González-Neira, A., Greene, M.H., Gschwantler-Kaulich, D., Hahnen, E., Hamann, U., Hanson, H., Hentschel, J., Hogervorst, F.B., Hooning, M.J., Horvath, J., Hu, C., Hulick, P.J., Imyanitov, E.N., Isaacs, C., Izatt, L., Izquierdo, A., Jakubowska, A., James, P.A., Janavicius, R., John, E.M., Joseph, V., Karlan, B.Y., Kast, K., Koudijs, M., Kruse, T.A., Kwong, A., Laitman, Y., Lasset, C., Mensenkamp, A.R., Chenevix-Trench, G., Antoniou, A.C., Barnes, D.R., Rookus, Matti A., McGuffog, L., Leslie, G., Mooij, T.M., Dennis, J., Mavaddat, N., Adlard, J., Ahmed, M., Aittomäki, K., Andrieu, N., Andrulis, I.L., Arnold, N., Arun, B.K., Azzollini, J., Balmaña, J., Barkardottir, R.B., Barrowdale, D., Benitez, J., Berthet, P., Białkowska, K., Blanco, A.M., Blok, M.J., Bonanni, B., Boonen, S.E., Borg, Å., Bozsik, A., Bradbury, A.R., Brennan, P., Brewer, C., Brunet, J., Buys, S.S., Caldés, T., Caligo, M.A., Campbell, I., Christensen, L.L., Chung, W.K., Claes, K.B.M., Colas, C., Collonge-Rame, M.A., Cook, J., Daly, M.B., Davidson, R., Hoya, M. de la, Putter, R. de, Delnatte, C., Devilee, P., Diez, O., Ding, Y.C., Domchek, S.M., Dorfling, C.M., Dumont, M., Eeles, R., Ejlertsen, B., Engel, C., Evans, D.G., Faivre, L., Foretova, L., Fostira, F., Friedlander, M., Friedman, E., Frost, D., Ganz, P.A., Garber, J., Gehrig, A., Gerdes, A.M., Gesta, P., Giraud, S., Glendon, G., Godwin, A.K., Goldgar, D.E., González-Neira, A., Greene, M.H., Gschwantler-Kaulich, D., Hahnen, E., Hamann, U., Hanson, H., Hentschel, J., Hogervorst, F.B., Hooning, M.J., Horvath, J., Hu, C., Hulick, P.J., Imyanitov, E.N., Isaacs, C., Izatt, L., Izquierdo, A., Jakubowska, A., James, P.A., Janavicius, R., John, E.M., Joseph, V., Karlan, B.Y., Kast, K., Koudijs, M., Kruse, T.A., Kwong, A., Laitman, Y., Lasset, C., Mensenkamp, A.R., Chenevix-Trench, G., and Antoniou, A.C.
Abstract: Contains fulltext : 229292.pdf (Publisher’s version ) (Open Access), PURPOSE: We assessed the associations between population-based polygenic risk scores (PRS) for breast (BC) or epithelial ovarian cancer (EOC) with cancer risks for BRCA1 and BRCA2 pathogenic variant carriers. METHODS: Retrospective cohort data on 18,935 BRCA1 and 12,339 BRCA2 female pathogenic variant carriers of European ancestry were available. Three versions of a 313 single-nucleotide polymorphism (SNP) BC PRS were evaluated based on whether they predict overall, estrogen receptor (ER)-negative, or ER-positive BC, and two PRS for overall or high-grade serous EOC. Associations were validated in a prospective cohort. RESULTS: The ER-negative PRS showed the strongest association with BC risk for BRCA1 carriers (hazard ratio [HR] per standard deviation = 1.29 [95% CI 1.25-1.33], P = 3×10(-72)). For BRCA2, the strongest association was with overall BC PRS (HR = 1.31 [95% CI 1.27-1.36], P = 7×10(-50)). HR estimates decreased significantly with age and there was evidence for differences in associations by predicted variant effects on protein expression. The HR estimates were smaller than general population estimates. The high-grade serous PRS yielded the strongest associations with EOC risk for BRCA1 (HR = 1.32 [95% CI 1.25-1.40], P = 3×10(-22)) and BRCA2 (HR = 1.44 [95% CI 1.30-1.60], P = 4×10(-12)) carriers. The associations in the prospective cohort were similar. CONCLUSION: Population-based PRS are strongly associated with BC and EOC risks for BRCA1/2 carriers and predict substantial absolute risk differences for women at PRS distribution extremes.
Published: 2020

18. Association of genomic domains in BRCA1 and BRCA2 with prostate cancer risk and aggressiveness.

Author: Engel C., Schmutzler R.K., Schuster H., Senter L., Seynaeve C.M., Shah P.D., Sharma P., Shin V.Y., Silvestri V., Simard J., Singer C.F., Skytte A.-B., Snape K., Solano A.R., Soucy P., Southey M.C., Spurdle A.B., Steele L., Steinemann D., Stoppa-Lyonnet D., Stradella A., Sunde L., Sutter C., Tan Y.Y., Teixeira M.R., Teo S.H., Thomassen M., Tibiletti M.G., Tischkowitz M., Tognazzo S., Toland A.E., Tommasi S., Torres D., Toss A., Trainer A.H., Tung N., Van Asperen C.J., Van Der Baan F.H., Van Der Kolk L.E., Van Der Luijt R.B., Van Hest L.P., Varesco L., Varon-Mateeva R., Viel A., Vierstrate J., Villa R., Von Wachenfeldt A., Wagner P., Wang-Gohrke S., Wappenschmidt B., Weitzel J.N., Wieme G., Yadav S., Yannoukakos D., Yoon S.-Y., Zanzottera C., Zorn K.K., D'Amico A.V., Freedman M.L., Pomerantz M.M., Chenevix-Trench G., Antoniou A.C., Neuhausen S.L., Ottini L., Nielsen H.R., Rebbeck T.R., Patel V.L., Busch E.L., Friebel T.M., Cronin A., Leslie G., McGuffog L., Adlard J., Agata S., Agnarsson B.A., Ahmed M., Aittom K., Alducci E., Andrulis I.L., Arason A., Arnold N., Artioli G., Arver B., Auber B., Azzollini J., Balmana J., Barkardottir R.B., Barnes D.R., Barroso A., Barrowdale D., Belotti M., Benitez J., Bertelsen B., Blok M.J., Bodrogi I., Bonadona V., Bonanni B., Bondavalli D., Boonen S.E., Borde J., Borg A., Bradbury A.R., Brady A., Brewer C., Brunet J., Buecher B., Buys S.S., Cabezas-Camarero S., Caldes T., Caliebe A., Caligo M.A., Calvello M., Campbell I.G., Carnevali I., Carrasco E., Chan T.L., Chu A.T.W., Chung W.K., Claes K.B.M., Cook J., Cortesi L., Couch F.J., Daly M.B., Damante G., Darder E., Davidson R., De La Hoya M., Della Puppa L., Dennis J., Diez O., Ding Y.C., Ditsch N., Domchek S.M., Donaldson A., Dworniczak B., Easton D.F., Eccles D.M., Eeles R.A., Ehrencrona H., Ejlertsen B., Evans D.G., Faivre L., Faust U., Feliubadalo L., Foretova L., Fostira F., Fountzilas G., Frost D., Garcia-Barberan V., Garre P., Gauthier-Villars M., Geczi L., Gehrig A., Gerdes A.-M., Gesta P., Giannini G., Glendon G., Godwin A.K., Goldgar D.E., Greene M.H., Gutierrez-Barrera A.M., Hahnen E., Hamann U., Hauke J., Herold N., Hogervorst F.B.L., Honisch E., Hopper J.L., Hulick P.J., Izatt L., Jager A., James P., Janavicius R., Jensen U.B., Jensen T.D., Johannsson O.Th., John E.M., Joseph V., Kang E., Kast K., Kiiski J.I., Kim S.-W., Kim Z., Ko K.-P., Konstantopoulou I., Kramer G., Krogh L., Kruse T.A., Kwong A., Larsen M., Lasset C., Lautrup C., Lazaro C., Lee J., Lee J.W., Lee M.H., Lemke J., Lesueur F., Liljegren A., Lindblom A., Llovet P., Lopez-Fernandez A., Lopez-Perolio I., Lorca V., Loud J.T., Ma E.S.K., Mai P.L., Manoukian S., Mari V., Martin L., Matricardi L., Mebirouk N., Medici V., Meijers-Heijboer H.E.J., Meindl A., Mensenkamp A.R., Miller C., Gomes D.M., Montagna M., Mooij T.M., Moserle L., Mouret-Fourme E., Mulligan A.M., Nathanson K.L., Navratilova M., Nevanlinna H., Niederacher D., Cilius Nielsen F.C., Nikitina-Zake L., Offit K., Olah E., Olopade O.I., Ong K.-R., Osorio A., Ott C.-E., Palli D., Park S.K., Parsons M.T., Pedersen I.S., Peissel B., Peixoto A., Perez-Segura P., Peterlongo P., Petersen A.H., Porteous M.E., Pujana M.A., Radice P., Ramser J., Rantala J., Rashid M.U., Rhiem K., Rizzolo P., Robson M.E., Rookus M.A., Rossing C.M., Ruddy K.J., Santos C., Saule C., Scarpitta R., Engel C., Schmutzler R.K., Schuster H., Senter L., Seynaeve C.M., Shah P.D., Sharma P., Shin V.Y., Silvestri V., Simard J., Singer C.F., Skytte A.-B., Snape K., Solano A.R., Soucy P., Southey M.C., Spurdle A.B., Steele L., Steinemann D., Stoppa-Lyonnet D., Stradella A., Sunde L., Sutter C., Tan Y.Y., Teixeira M.R., Teo S.H., Thomassen M., Tibiletti M.G., Tischkowitz M., Tognazzo S., Toland A.E., Tommasi S., Torres D., Toss A., Trainer A.H., Tung N., Van Asperen C.J., Van Der Baan F.H., Van Der Kolk L.E., Van Der Luijt R.B., Van Hest L.P., Varesco L., Varon-Mateeva R., Viel A., Vierstrate J., Villa R., Von Wachenfeldt A., Wagner P., Wang-Gohrke S., Wappenschmidt B., Weitzel J.N., Wieme G., Yadav S., Yannoukakos D., Yoon S.-Y., Zanzottera C., Zorn K.K., D'Amico A.V., Freedman M.L., Pomerantz M.M., Chenevix-Trench G., Antoniou A.C., Neuhausen S.L., Ottini L., Nielsen H.R., Rebbeck T.R., Patel V.L., Busch E.L., Friebel T.M., Cronin A., Leslie G., McGuffog L., Adlard J., Agata S., Agnarsson B.A., Ahmed M., Aittom K., Alducci E., Andrulis I.L., Arason A., Arnold N., Artioli G., Arver B., Auber B., Azzollini J., Balmana J., Barkardottir R.B., Barnes D.R., Barroso A., Barrowdale D., Belotti M., Benitez J., Bertelsen B., Blok M.J., Bodrogi I., Bonadona V., Bonanni B., Bondavalli D., Boonen S.E., Borde J., Borg A., Bradbury A.R., Brady A., Brewer C., Brunet J., Buecher B., Buys S.S., Cabezas-Camarero S., Caldes T., Caliebe A., Caligo M.A., Calvello M., Campbell I.G., Carnevali I., Carrasco E., Chan T.L., Chu A.T.W., Chung W.K., Claes K.B.M., Cook J., Cortesi L., Couch F.J., Daly M.B., Damante G., Darder E., Davidson R., De La Hoya M., Della Puppa L., Dennis J., Diez O., Ding Y.C., Ditsch N., Domchek S.M., Donaldson A., Dworniczak B., Easton D.F., Eccles D.M., Eeles R.A., Ehrencrona H., Ejlertsen B., Evans D.G., Faivre L., Faust U., Feliubadalo L., Foretova L., Fostira F., Fountzilas G., Frost D., Garcia-Barberan V., Garre P., Gauthier-Villars M., Geczi L., Gehrig A., Gerdes A.-M., Gesta P., Giannini G., Glendon G., Godwin A.K., Goldgar D.E., Greene M.H., Gutierrez-Barrera A.M., Hahnen E., Hamann U., Hauke J., Herold N., Hogervorst F.B.L., Honisch E., Hopper J.L., Hulick P.J., Izatt L., Jager A., James P., Janavicius R., Jensen U.B., Jensen T.D., Johannsson O.Th., John E.M., Joseph V., Kang E., Kast K., Kiiski J.I., Kim S.-W., Kim Z., Ko K.-P., Konstantopoulou I., Kramer G., Krogh L., Kruse T.A., Kwong A., Larsen M., Lasset C., Lautrup C., Lazaro C., Lee J., Lee J.W., Lee M.H., Lemke J., Lesueur F., Liljegren A., Lindblom A., Llovet P., Lopez-Fernandez A., Lopez-Perolio I., Lorca V., Loud J.T., Ma E.S.K., Mai P.L., Manoukian S., Mari V., Martin L., Matricardi L., Mebirouk N., Medici V., Meijers-Heijboer H.E.J., Meindl A., Mensenkamp A.R., Miller C., Gomes D.M., Montagna M., Mooij T.M., Moserle L., Mouret-Fourme E., Mulligan A.M., Nathanson K.L., Navratilova M., Nevanlinna H., Niederacher D., Cilius Nielsen F.C., Nikitina-Zake L., Offit K., Olah E., Olopade O.I., Ong K.-R., Osorio A., Ott C.-E., Palli D., Park S.K., Parsons M.T., Pedersen I.S., Peissel B., Peixoto A., Perez-Segura P., Peterlongo P., Petersen A.H., Porteous M.E., Pujana M.A., Radice P., Ramser J., Rantala J., Rashid M.U., Rhiem K., Rizzolo P., Robson M.E., Rookus M.A., Rossing C.M., Ruddy K.J., Santos C., Saule C., and Scarpitta R.
Abstract: Pathogenic sequence variants (PSV) in BRCA1 or BRCA2 (BRCA1/2) are associated with increased risk and severity of prostate cancer. We evaluated whether PSVs in BRCA1/2 were associated with risk of overall prostate cancer or high grade (Gleason 8) prostate cancer using an international sample of 65 BRCA1 and 171 BRCA2 male PSV carriers with prostate cancer, and 3,388 BRCA1 and 2,880 BRCA2 male PSV carriers without prostate cancer. PSVs in the 30 region of BRCA2 (c.7914) were significantly associated with elevated risk of prostate cancer compared with reference bin c.1001c.7913 [HR 1/4 1.78; 95% confidence interval (CI), 1.25-2.52; P 1/4 0.001], as well as elevated risk of Gleason 8 prostate cancer (HR 1/4 3.11; 95% CI, 1.63-5.95; P 1/4 0.001). c.756-c.1000 was also associated with elevated prostate cancer risk (HR 1/4 2.83; 95% CI, 1.71-4.68; P 1/4 0.00004) and elevated risk of Gleason 8 prostate cancer (HR 1/4 4.95; 95% CI, 2.12-11.54; P 1/4 0.0002). No genotype-phenotype associations were detected for PSVs in BRCA1. These results demonstrate that specific BRCA2 PSVs may be associated with elevated risk of developing aggressive prostate cancer.Copyright © 2020 American Association for Cancer Research.
Published: 2020

19. Assessment of polygenic architecture and risk prediction based on common variants across fourteen cancers.

Author: Houlston R., Choudhury P.P., Easton D.F., Milne R.L., Simard J., Hall P., Michailidou K., Dennis J., Schmidt M.K., Chang-Claude J., Gharahkhani P., Whiteman D., O'Mara T.A., Spurdle A.B., Thompson D.J., Tomlinson I., De Vivo I., Campbell P.T., Hoffmeister M., Jenkins M., Peters U., Hsu L., Gruber S.B., Casey G., Schmit S.L., Landi M.T., Law M.H., Iles M.M., Demenais F., Kumar R., MacGregor S., Bishop D.T., Ward S.V., Bondy M.L., Wiencke J.K., Melin B., Barnholtz-Sloan J., Kinnersley B., Wrensch M.R., Hung R.J., Caporaso N.E., Berndt S.I., Birmann B.M., Camp N.J., Kraft P., Rothman N., Slager S.L., Berchuck A., Pharoah P.D.P., Sellers T.A., Gayther S.A., Pearce C.L., Goode E.L., Schildkraut J.M., Moysich K.B., Amos C.I., Brennan P., McKay J., Amundadottir L.T., Jacobs E.J., Klein A.P., Petersen G.M., Risch H.A., Stolzenberg-Solomon R.Z., Wolpin B.M., Li D., Eeles R.A., Haiman C.A., Kote-Jarai Z., Schumacher F.R., Al Olama A.A., Purdue M.P., Scelo G., Dalgaard M.D., Greene M.H., Grotmol T., Kanetsky P.A., McGlynn K.A., Nathanson K.L., Turnbull C., Wiklund F., Chanock S.J., Chatterjee N., Garcia-Closas M., Zhang Y.D., Hurson A.N., Zhang H., Houlston R., Choudhury P.P., Easton D.F., Milne R.L., Simard J., Hall P., Michailidou K., Dennis J., Schmidt M.K., Chang-Claude J., Gharahkhani P., Whiteman D., O'Mara T.A., Spurdle A.B., Thompson D.J., Tomlinson I., De Vivo I., Campbell P.T., Hoffmeister M., Jenkins M., Peters U., Hsu L., Gruber S.B., Casey G., Schmit S.L., Landi M.T., Law M.H., Iles M.M., Demenais F., Kumar R., MacGregor S., Bishop D.T., Ward S.V., Bondy M.L., Wiencke J.K., Melin B., Barnholtz-Sloan J., Kinnersley B., Wrensch M.R., Hung R.J., Caporaso N.E., Berndt S.I., Birmann B.M., Camp N.J., Kraft P., Rothman N., Slager S.L., Berchuck A., Pharoah P.D.P., Sellers T.A., Gayther S.A., Pearce C.L., Goode E.L., Schildkraut J.M., Moysich K.B., Amos C.I., Brennan P., McKay J., Amundadottir L.T., Jacobs E.J., Klein A.P., Petersen G.M., Risch H.A., Stolzenberg-Solomon R.Z., Wolpin B.M., Li D., Eeles R.A., Haiman C.A., Kote-Jarai Z., Schumacher F.R., Al Olama A.A., Purdue M.P., Scelo G., Dalgaard M.D., Greene M.H., Grotmol T., Kanetsky P.A., McGlynn K.A., Nathanson K.L., Turnbull C., Wiklund F., Chanock S.J., Chatterjee N., Garcia-Closas M., Zhang Y.D., Hurson A.N., and Zhang H.
Abstract: Genome-wide association studies (GWAS) have led to the identification of hundreds of susceptibility loci across cancers, but the impact of further studies remains uncertain. Here we analyse summary-level data from GWAS of European ancestry across fourteen cancer sites to estimate the number of common susceptibility variants (polygenicity) and underlying effect-size distribution. All cancers show a high degree of polygenicity, involving at a minimum of thousands of loci. We project that sample sizes required to explain 80% of GWAS heritability vary from 60,000 cases for testicular to over 1,000,000 cases for lung cancer. The maximum relative risk achievable for subjects at the 99th risk percentile of underlying polygenic risk scores (PRS), compared to average risk, ranges from 12 for testicular to 2.5 for ovarian cancer. We show that PRS have potential for risk stratification for cancers of breast, colon and prostate, but less so for others because of modest heritability and lower incidence.Copyright © 2020, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.
Published: 2020

20. Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes.

Author: Ramus S.J., Carroll J.S., Schneeweiss A., Schoemaker M.J., Schottker B., Schurmann P., Scott C., Scott R.J., Senter L., Shah M., Sharma P., Shen C.-Y., Shu X.-O., Singer C.F., Slavin T.P., Smichkoska S., Spinelli J.J., Spurdle A.B., Sutter C., Swerdlow A.J., Tamimi R.M., Tan Y.Y., Tapper W.J., Taylor J., Teixeira M.R., Tengstrom M., Teo S.H., Terry M.B., Teule A., Thomassen M., Thull D.L., Toland A.E., Tollenaar R.A.E.M., Tomlinson I., Torres D., Torres-Mejia G., Troester M.A., Truong T., Tung N., Tzardi M., Ulmer H.-U., Vachon C.M., van der Kolk L.E., van Rensburg E.J., Vega A., Viel A., Vijai J., Vogel M.J., Wang Q., Wappenschmidt B., Weinberg C.R., Weitzel J.N., Wendt C., Wildiers H., Winqvist R., Wolk A., Wu A.H., Yannoukakos D., Zhang Y., Zheng W., Hunter D., Pharoah P.D.P., Chang-Claude J., Garcia-Closas M., Schmidt M.K., Kristensen V.N., French J.D., Antoniou A.C., Chenevix-Trench G., Simard J., Easton D.F., Kraft P., Allen J., Harris M., Fachal L., Aschard H., Beesley J., Barnes D.R., Kar S., Pooley K.A., Dennis J., Michailidou K., Turman C., Soucy P., Lemacon A., Lush M., Tyrer J.P., Ghoussaini M., Marjaneh M.M., Jiang X., Agata S., Aittomaki K., Alonso M.R., Andrulis I.L., Anton-Culver H., Antonenkova N.N., Arason A., Arndt V., Aronson K.J., Arun B.K., Auber B., Auer P.L., Azzollini J., Balmana J., Barkardottir R.B., Barrowdale D., Beeghly-Fadiel A., Benitez J., Bermisheva M., Bialkowska K., Blanco A.M., Blomqvist C., Blot W., Bogdanova N.V., Bojesen S.E., Bolla M.K., Bonanni B., Borg A., Bosse K., Brauch H., Brenner H., Briceno I., Brock I.W., Brooks-Wilson A., Bruning T., Burwinkel B., Buys S.S., Cai Q., Caldes T., Caligo M.A., Camp N.J., Campbell I., Carter B.D., Castelao J.E., Chiquette J., Christiansen H., Chung W.K., Claes K.B.M., Clarke C.L., Mari V., Berthet P., Castera L., Vaur D., Lallaoui H., Bignon Y.-J., Uhrhammer N., Bonadona V., Lasset C., Revillion F., Vennin P., Muller D., Gomes D.M., Ingster O., Coupier I., Pujol P., Collonge-Rame M.-A., Mortemousque I., Bera O., Rose M., Baurand A., Bertolone G., Faivre L., Dreyfus H., Leroux D., Venat-Bouvet L., Bezieau S., Delnatte C., Chiesa J., Gilbert-Dussardier B., Gesta P., Prieur F.P., Bronner M., Sokolowska J., Coulet F., Boutry-Kryza N., Calender A., Giraud S., Leone M., Fert-Ferrer S., Stoppa-Lyonnet D., Jiao Y., Lesueur F.L., Mebirouk N., Barouk-Simonet E., Bubien V., Longy M., Sevenet N., Gladieff L., Toulas C., Reimineras A., Sobol H., Paillerets B.B.-D., Cabaret O., Caron O., Guillaud-Bataille M., Rouleau E., Belotti M., Buecher B., Caputo S., Colas C., Pauw A.D., Fourme E., Gauthier-Villars M., Golmard L., Moncoutier V., Saule C., Donaldson A., Murray A., Brady A., Brewer C., Pottinger C., Miller C., Gallagher D., Gregory H., Cook J., Eason J., Adlard J., Barwell J., Ong K.-R., Snape K., Walker L., Izatt L., Side L., Tischkowitz M., Rogers M.T., Porteous M.E., Ahmed M., Morrison P.J., Brennan P., Eeles R., Davidson R., Collee J.M., Cornelissen S., Couch F.J., Cox A., Cross S.S., Cybulski C., Czene K., Daly M.B., de la Hoya M., Devilee P., Diez O., Ding Y.C., Dite G.S., Domchek S.M., Dork T., dos-Santos-Silva I., Droit A., Dubois S., Dumont M., Duran M., Durcan L., Dwek M., Eccles D.M., Engel C., Eriksson M., Evans D.G., Fasching P.A., Fletcher O., Floris G., Flyger H., Foretova L., Foulkes W.D., Friedman E., Fritschi L., Frost D., Gabrielson M., Gago-Dominguez M., Gambino G., Ganz P.A., Gapstur S.M., Garber J., Garcia-Saenz J.A., Gaudet M.M., Georgoulias V., Giles G., Glendon G., Godwin A.K., Goldberg M.S., Goldgar D.E., Gonzalez-Neira A., Tibiletti M.G., Greene M.H., Grip M., Gronwald J., Grundy A., Guenel P., Hahnen E., Haiman C.A., Hakansson N., Hall P., Hamann U., Harrington P.A., Hartikainen J.M., Hartman M., He W., Healey C.S., Heemskerk-Gerritsen B.A.M., Heyworth J., Hillemanns P., Hogervorst F.B.L., Hollestelle A., Hooning M., Hopper J., Howell A., Huang G., Hulick P.J., Imyanitov E.N., Sexton A., Christian A., Trainer A., Spigelman A., Fellows A., Shelling A., Fazio A.D., Blackburn A., Crook A., Meiser B., Patterson B., Clarke C., Saunders C., Hunt C., Amor D., Marsh D., Edkins E., Salisbury E., Haan E., Neidermayr E., Macrea F., Farshid G., Lindeman G., Trench G., Mann G., Gill G., Thorne H., Hickie I., Winship I., Flanagan J., Kollias J., Visvader J., Stone J., Burke J., Saunus J., Forbes J., French J., Tucker K., Wu K., Phillips K., Lipton L., Andrews L., Lobb L., Kentwell M., Spurdle M., Cummings M., Gleeson M., Jenkins M., Young M.A., Delatycki M., Wallis M., Burgess M., Price M., Brown M., Southey M., Bogwitz M., Field M., Friedlander M., Gattas M., Saleh M., Hayward N., Pachter N., Cohen P., Duijf P., James P., Simpson P., Fong P., Butow P., Williams R., Kefford R., Scott R., Milne R.L., Balleine R., Dawson S.-J., Lok S., O'Connell S., Greening S., Nightingale S., Edwards S., Fox S., McLachlan S.-A., Lakhani S., Antill Y., Aalfs C., Meijers-Heijboer H., van Engelen K., Gille H., Boere I., Collee M., van Deurzen C., Obdeijn I.-M., van den Ouweland A., Seynaeve C., Siesling S., Verloop J., van Asperen C., van Cronenburg T., Blok R., de Boer M., Garcia E.G., Adank M., Hogervorst F., Jenner D., van Leeuwen F., Rookus M., Russell N., Schmidt M., van den Belt-Dusebout S., Kets C., Mensenkamp A., de Bock T., van der Hout A., Mourits M., Oosterwijk J., Ausems M., Koudijs M., Baxter R., Yip D., Carpenter J., Davis A., Pathmanathan N., Graham D., Sachchithananthan M., Isaacs C., Iwasaki M., Jager A., Jakimovska M., Jakubowska A., Janavicius R., Jankowitz R.C., John E.M., Johnson N., Jones M.E., Jukkola-Vuorinen A., Jung A., Kaaks R., Kang D., Kapoor P.M., Karlan B.Y., Keeman R., Kerin M.J., Khusnutdinova E., Kiiski J.I., Kirk J., Kitahara C.M., Ko Y.-D., Konstantopoulou I., Kosma V.-M., Koutros S., Kubelka-Sabit K., Kwong A., Kyriacou K., Laitman Y., Lambrechts D., Lee E., Leslie G., Lester J., Lesueur F., Lindblom A., Lo W.-Y., Long J., Lophatananon A., Loud J.T., Lubinski J., MacInnis R.J., Maishman T., Makalic E., Mannermaa A., Manoochehri M., Manoukian S., Margolin S., Martinez M.E., Matsuo K., Maurer T., Mavroudis D., Mayes R., McGuffog L., McLean C., Meindl A., Miller A., Miller N., Montagna M., Moreno F., Muir K., Mulligan A.M., Munoz-Garzon V.M., Muranen T.A., Narod S.A., Nassir R., Nathanson K.L., Neuhausen S.L., Nevanlinna H., Neven P., Nielsen F.C., Nikitina-Zake L., Norman A., Offit K., Olah E., Olopade O.I., Olsson H., Orr N., Osorio A., Pankratz V.S., Papp J., Park S.K., Park-Simon T.-W., Parsons M.T., Paul J., Pedersen I.S., Peissel B., Peshkin B., Peterlongo P., Peto J., Plaseska-Karanfilska D., Prajzendanc K., Prentice R., Presneau N., Prokofyeva D., Pujana M.A., Pylkas K., Radice P., Canzian F., Rantala J., Rau-Murthy R., Rennert G., Risch H.A., Robson M., Romero A., Rossing M., Saloustros E., Sanchez-Herrero E., Sandler D.P., Santamarina M., Sawyer E.J., Scheuner M.T., Schmidt D.F., Schmutzler R.K., Ramus S.J., Carroll J.S., Schneeweiss A., Schoemaker M.J., Schottker B., Schurmann P., Scott C., Scott R.J., Senter L., Shah M., Sharma P., Shen C.-Y., Shu X.-O., Singer C.F., Slavin T.P., Smichkoska S., Spinelli J.J., Spurdle A.B., Sutter C., Swerdlow A.J., Tamimi R.M., Tan Y.Y., Tapper W.J., Taylor J., Teixeira M.R., Tengstrom M., Teo S.H., Terry M.B., Teule A., Thomassen M., Thull D.L., Toland A.E., Tollenaar R.A.E.M., Tomlinson I., Torres D., Torres-Mejia G., Troester M.A., Truong T., Tung N., Tzardi M., Ulmer H.-U., Vachon C.M., van der Kolk L.E., van Rensburg E.J., Vega A., Viel A., Vijai J., Vogel M.J., Wang Q., Wappenschmidt B., Weinberg C.R., Weitzel J.N., Wendt C., Wildiers H., Winqvist R., Wolk A., Wu A.H., Yannoukakos D., Zhang Y., Zheng W., Hunter D., Pharoah P.D.P., Chang-Claude J., Garcia-Closas M., Schmidt M.K., Kristensen V.N., French J.D., Antoniou A.C., Chenevix-Trench G., Simard J., Easton D.F., Kraft P., Allen J., Harris M., Fachal L., Aschard H., Beesley J., Barnes D.R., Kar S., Pooley K.A., Dennis J., Michailidou K., Turman C., Soucy P., Lemacon A., Lush M., Tyrer J.P., Ghoussaini M., Marjaneh M.M., Jiang X., Agata S., Aittomaki K., Alonso M.R., Andrulis I.L., Anton-Culver H., Antonenkova N.N., Arason A., Arndt V., Aronson K.J., Arun B.K., Auber B., Auer P.L., Azzollini J., Balmana J., Barkardottir R.B., Barrowdale D., Beeghly-Fadiel A., Benitez J., Bermisheva M., Bialkowska K., Blanco A.M., Blomqvist C., Blot W., Bogdanova N.V., Bojesen S.E., Bolla M.K., Bonanni B., Borg A., Bosse K., Brauch H., Brenner H., Briceno I., Brock I.W., Brooks-Wilson A., Bruning T., Burwinkel B., Buys S.S., Cai Q., Caldes T., Caligo M.A., Camp N.J., Campbell I., Carter B.D., Castelao J.E., Chiquette J., Christiansen H., Chung W.K., Claes K.B.M., Clarke C.L., Mari V., Berthet P., Castera L., Vaur D., Lallaoui H., Bignon Y.-J., Uhrhammer N., Bonadona V., Lasset C., Revillion F., Vennin P., Muller D., Gomes D.M., Ingster O., Coupier I., Pujol P., Collonge-Rame M.-A., Mortemousque I., Bera O., Rose M., Baurand A., Bertolone G., Faivre L., Dreyfus H., Leroux D., Venat-Bouvet L., Bezieau S., Delnatte C., Chiesa J., Gilbert-Dussardier B., Gesta P., Prieur F.P., Bronner M., Sokolowska J., Coulet F., Boutry-Kryza N., Calender A., Giraud S., Leone M., Fert-Ferrer S., Stoppa-Lyonnet D., Jiao Y., Lesueur F.L., Mebirouk N., Barouk-Simonet E., Bubien V., Longy M., Sevenet N., Gladieff L., Toulas C., Reimineras A., Sobol H., Paillerets B.B.-D., Cabaret O., Caron O., Guillaud-Bataille M., Rouleau E., Belotti M., Buecher B., Caputo S., Colas C., Pauw A.D., Fourme E., Gauthier-Villars M., Golmard L., Moncoutier V., Saule C., Donaldson A., Murray A., Brady A., Brewer C., Pottinger C., Miller C., Gallagher D., Gregory H., Cook J., Eason J., Adlard J., Barwell J., Ong K.-R., Snape K., Walker L., Izatt L., Side L., Tischkowitz M., Rogers M.T., Porteous M.E., Ahmed M., Morrison P.J., Brennan P., Eeles R., Davidson R., Collee J.M., Cornelissen S., Couch F.J., Cox A., Cross S.S., Cybulski C., Czene K., Daly M.B., de la Hoya M., Devilee P., Diez O., Ding Y.C., Dite G.S., Domchek S.M., Dork T., dos-Santos-Silva I., Droit A., Dubois S., Dumont M., Duran M., Durcan L., Dwek M., Eccles D.M., Engel C., Eriksson M., Evans D.G., Fasching P.A., Fletcher O., Floris G., Flyger H., Foretova L., Foulkes W.D., Friedman E., Fritschi L., Frost D., Gabrielson M., Gago-Dominguez M., Gambino G., Ganz P.A., Gapstur S.M., Garber J., Garcia-Saenz J.A., Gaudet M.M., Georgoulias V., Giles G., Glendon G., Godwin A.K., Goldberg M.S., Goldgar D.E., Gonzalez-Neira A., Tibiletti M.G., Greene M.H., Grip M., Gronwald J., Grundy A., Guenel P., Hahnen E., Haiman C.A., Hakansson N., Hall P., Hamann U., Harrington P.A., Hartikainen J.M., Hartman M., He W., Healey C.S., Heemskerk-Gerritsen B.A.M., Heyworth J., Hillemanns P., Hogervorst F.B.L., Hollestelle A., Hooning M., Hopper J., Howell A., Huang G., Hulick P.J., Imyanitov E.N., Sexton A., Christian A., Trainer A., Spigelman A., Fellows A., Shelling A., Fazio A.D., Blackburn A., Crook A., Meiser B., Patterson B., Clarke C., Saunders C., Hunt C., Amor D., Marsh D., Edkins E., Salisbury E., Haan E., Neidermayr E., Macrea F., Farshid G., Lindeman G., Trench G., Mann G., Gill G., Thorne H., Hickie I., Winship I., Flanagan J., Kollias J., Visvader J., Stone J., Burke J., Saunus J., Forbes J., French J., Tucker K., Wu K., Phillips K., Lipton L., Andrews L., Lobb L., Kentwell M., Spurdle M., Cummings M., Gleeson M., Jenkins M., Young M.A., Delatycki M., Wallis M., Burgess M., Price M., Brown M., Southey M., Bogwitz M., Field M., Friedlander M., Gattas M., Saleh M., Hayward N., Pachter N., Cohen P., Duijf P., James P., Simpson P., Fong P., Butow P., Williams R., Kefford R., Scott R., Milne R.L., Balleine R., Dawson S.-J., Lok S., O'Connell S., Greening S., Nightingale S., Edwards S., Fox S., McLachlan S.-A., Lakhani S., Antill Y., Aalfs C., Meijers-Heijboer H., van Engelen K., Gille H., Boere I., Collee M., van Deurzen C., Obdeijn I.-M., van den Ouweland A., Seynaeve C., Siesling S., Verloop J., van Asperen C., van Cronenburg T., Blok R., de Boer M., Garcia E.G., Adank M., Hogervorst F., Jenner D., van Leeuwen F., Rookus M., Russell N., Schmidt M., van den Belt-Dusebout S., Kets C., Mensenkamp A., de Bock T., van der Hout A., Mourits M., Oosterwijk J., Ausems M., Koudijs M., Baxter R., Yip D., Carpenter J., Davis A., Pathmanathan N., Graham D., Sachchithananthan M., Isaacs C., Iwasaki M., Jager A., Jakimovska M., Jakubowska A., Janavicius R., Jankowitz R.C., John E.M., Johnson N., Jones M.E., Jukkola-Vuorinen A., Jung A., Kaaks R., Kang D., Kapoor P.M., Karlan B.Y., Keeman R., Kerin M.J., Khusnutdinova E., Kiiski J.I., Kirk J., Kitahara C.M., Ko Y.-D., Konstantopoulou I., Kosma V.-M., Koutros S., Kubelka-Sabit K., Kwong A., Kyriacou K., Laitman Y., Lambrechts D., Lee E., Leslie G., Lester J., Lesueur F., Lindblom A., Lo W.-Y., Long J., Lophatananon A., Loud J.T., Lubinski J., MacInnis R.J., Maishman T., Makalic E., Mannermaa A., Manoochehri M., Manoukian S., Margolin S., Martinez M.E., Matsuo K., Maurer T., Mavroudis D., Mayes R., McGuffog L., McLean C., Meindl A., Miller A., Miller N., Montagna M., Moreno F., Muir K., Mulligan A.M., Munoz-Garzon V.M., Muranen T.A., Narod S.A., Nassir R., Nathanson K.L., Neuhausen S.L., Nevanlinna H., Neven P., Nielsen F.C., Nikitina-Zake L., Norman A., Offit K., Olah E., Olopade O.I., Olsson H., Orr N., Osorio A., Pankratz V.S., Papp J., Park S.K., Park-Simon T.-W., Parsons M.T., Paul J., Pedersen I.S., Peissel B., Peshkin B., Peterlongo P., Peto J., Plaseska-Karanfilska D., Prajzendanc K., Prentice R., Presneau N., Prokofyeva D., Pujana M.A., Pylkas K., Radice P., Canzian F., Rantala J., Rau-Murthy R., Rennert G., Risch H.A., Robson M., Romero A., Rossing M., Saloustros E., Sanchez-Herrero E., Sandler D.P., Santamarina M., Sawyer E.J., Scheuner M.T., Schmidt D.F., and Schmutzler R.K.
Abstract: Genome-wide association studies have identified breast cancer risk variants in over 150 genomic regions, but the mechanisms underlying risk remain largely unknown. These regions were explored by combining association analysis with in silico genomic feature annotations. We defined 205 independent risk-associated signals with the set of credible causal variants in each one. In parallel, we used a Bayesian approach (PAINTOR) that combines genetic association, linkage disequilibrium and enriched genomic features to determine variants with high posterior probabilities of being causal. Potentially causal variants were significantly over-represented in active gene regulatory regions and transcription factor binding sites. We applied our INQUSIT pipeline for prioritizing genes as targets of those potentially causal variants, using gene expression (expression quantitative trait loci), chromatin interaction and functional annotations. Known cancer drivers, transcription factors and genes in the developmental, apoptosis, immune system and DNA integrity checkpoint gene ontology pathways were over-represented among the highest-confidence target genes.Copyright © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.
Published: 2020

21. Transcriptome-wide association study of breast cancer risk by estrogen-receptor status.

Author: Eriksson M., Peterlongo P., Peto J., Pharoah P.D.P., Phillips K.-A., Plaseska-Karanfilska D., Poppe B., Pradhan N., Prajzendanc K., Presneau N., Punie K., Pylkas K., Radice P., Rantala J., Rashid M.U., Rennert G., Risch H.A., Robson M., Romero A., Saloustros E., Sandler D.P., Santos C., Sawyer E.J., Schmidt M.K., Schmidt D.F., Schmutzler R.K., Schoemaker M.J., Scott R.J., Sharma P., Shu X.-O., Simard J., Singer C.F., Skytte A.-B., Soucy P., Southey M.C., Spinelli J.J., Spurdle A.B., Stone J., Swerdlow A.J., Tapper W.J., Taylor J.A., Teixeira M.R., Terry M.B., Teule A., Thomassen M., Thone K., Thull D.L., Tischkowitz M., Toland A.E., Tollenaar R.A.E.M., Torres D., Truong T., Tung N., Vachon C.M., van Asperen C.J., van den Ouweland A.M.W., van Rensburg E.J., Vega A., Viel A., Vieiro-Balo P., Wang Q., Wappenschmidt B., Weinberg C.R., Weitzel J.N., Wendt C., Winqvist R., Yang X.R., Yannoukakos D., Ziogas A., Milne R.L., Easton D.F., Chenevix-Trench G., Zheng W., Kraft P., Jiang X., Feng H., Gusev A., Pasaniuc B., Wu L., Long J., Abu-full Z., Aittomaki K., Andrulis I.L., Anton-Culver H., Antoniou A.C., Arason A., Arndt V., Aronson K.J., Arun B.K., Asseryanis E., Auer P.L., Azzollini J., Balmana J., Barkardottir R.B., Barnes D.R., Barrowdale D., Beckmann M.W., Behrens S., Benitez J., Bermisheva M., Bialkowska K., Blanco A., Blomqvist C., Boeckx B., Bogdanova N.V., Bojesen S.E., Bolla M.K., Bonanni B., Borg A., Brauch H., Brenner H., Briceno I., Broeks A., Bruning T., Burwinkel B., Cai Q., Caldes T., Caligo M.A., Campbell I., Canisius S., Campa D., Carter B.D., Carter J., Castelao J.E., Chang-Claude J., Chanock S.J., Christiansen H., Chung W.K., Claes K.B.M., Clarke C.L., Couch F.J., Cox A., Cross S.S., Cybulski C., Czene K., Daly M.B., de la Hoya M., De Leeneer K., Dennis J., Devilee P., Diez O., Domchek S.M., Dork T., dos-Santos-Silva I., Dunning A.M., Dwek M., Eccles D.M., Ejlertsen B., Ellberg C., Engel C., Fasching P.A., Fletcher O., Flyger H., Fostira F., Friedman E., Fritschi L., Frost D., Gabrielson M., Ganz P.A., Gapstur S.M., Garber J., Garcia-Closas M., Garcia-Saenz J.A., Gaudet M.M., Giles G.G., Glendon G., Godwin A.K., Goldberg M.S., Goldgar D.E., Gonzalez-Neira A., Greene M.H., Gronwald J., Guenel P., Haiman C.A., Hall P., Hamann U., Hake C., He W., Heyworth J., Hogervorst F.B.L., Hollestelle A., Hooning M.J., Hoover R.N., Hopper J.L., Huang G., Hulick P.J., Humphreys K., Imyanitov E.N., Isaacs C., Jakimovska M., Jakubowska A., James P., Janavicius R., Jankowitz R.C., John E.M., Johnson N., Joseph V., Jung A., Karlan B.Y., Khusnutdinova E., Kiiski J.I., Konstantopoulou I., Kristensen V.N., Laitman Y., Lambrechts D., Lazaro C., Leroux D., Leslie G., Lester J., Lesueur F., Lindor N., Lindstrom S., Lo W.-Y., Loud J.T., Lubinski J., Makalic E., Mannermaa A., Manoochehri M., Manoukian S., Margolin S., Martens J.W.M., Martinez M.E., Matricardi L., Maurer T., Mavroudis D., McGuffog L., Meindl A., Menon U., Michailidou K., Kapoor P.M., Miller A., Montagna M., Moreno F., Moserle L., Mulligan A.M., Muranen T.A., Nathanson K.L., Neuhausen S.L., Nevanlinna H., Nevelsteen I., Nielsen F.C., Nikitina-Zake L., Offit K., Olah E., Olopade O.I., Olsson H., Osorio A., Papp J., Park-Simon T.-W., Parsons M.T., Pedersen I.S., Peixoto A., Eriksson M., Peterlongo P., Peto J., Pharoah P.D.P., Phillips K.-A., Plaseska-Karanfilska D., Poppe B., Pradhan N., Prajzendanc K., Presneau N., Punie K., Pylkas K., Radice P., Rantala J., Rashid M.U., Rennert G., Risch H.A., Robson M., Romero A., Saloustros E., Sandler D.P., Santos C., Sawyer E.J., Schmidt M.K., Schmidt D.F., Schmutzler R.K., Schoemaker M.J., Scott R.J., Sharma P., Shu X.-O., Simard J., Singer C.F., Skytte A.-B., Soucy P., Southey M.C., Spinelli J.J., Spurdle A.B., Stone J., Swerdlow A.J., Tapper W.J., Taylor J.A., Teixeira M.R., Terry M.B., Teule A., Thomassen M., Thone K., Thull D.L., Tischkowitz M., Toland A.E., Tollenaar R.A.E.M., Torres D., Truong T., Tung N., Vachon C.M., van Asperen C.J., van den Ouweland A.M.W., van Rensburg E.J., Vega A., Viel A., Vieiro-Balo P., Wang Q., Wappenschmidt B., Weinberg C.R., Weitzel J.N., Wendt C., Winqvist R., Yang X.R., Yannoukakos D., Ziogas A., Milne R.L., Easton D.F., Chenevix-Trench G., Zheng W., Kraft P., Jiang X., Feng H., Gusev A., Pasaniuc B., Wu L., Long J., Abu-full Z., Aittomaki K., Andrulis I.L., Anton-Culver H., Antoniou A.C., Arason A., Arndt V., Aronson K.J., Arun B.K., Asseryanis E., Auer P.L., Azzollini J., Balmana J., Barkardottir R.B., Barnes D.R., Barrowdale D., Beckmann M.W., Behrens S., Benitez J., Bermisheva M., Bialkowska K., Blanco A., Blomqvist C., Boeckx B., Bogdanova N.V., Bojesen S.E., Bolla M.K., Bonanni B., Borg A., Brauch H., Brenner H., Briceno I., Broeks A., Bruning T., Burwinkel B., Cai Q., Caldes T., Caligo M.A., Campbell I., Canisius S., Campa D., Carter B.D., Carter J., Castelao J.E., Chang-Claude J., Chanock S.J., Christiansen H., Chung W.K., Claes K.B.M., Clarke C.L., Couch F.J., Cox A., Cross S.S., Cybulski C., Czene K., Daly M.B., de la Hoya M., De Leeneer K., Dennis J., Devilee P., Diez O., Domchek S.M., Dork T., dos-Santos-Silva I., Dunning A.M., Dwek M., Eccles D.M., Ejlertsen B., Ellberg C., Engel C., Fasching P.A., Fletcher O., Flyger H., Fostira F., Friedman E., Fritschi L., Frost D., Gabrielson M., Ganz P.A., Gapstur S.M., Garber J., Garcia-Closas M., Garcia-Saenz J.A., Gaudet M.M., Giles G.G., Glendon G., Godwin A.K., Goldberg M.S., Goldgar D.E., Gonzalez-Neira A., Greene M.H., Gronwald J., Guenel P., Haiman C.A., Hall P., Hamann U., Hake C., He W., Heyworth J., Hogervorst F.B.L., Hollestelle A., Hooning M.J., Hoover R.N., Hopper J.L., Huang G., Hulick P.J., Humphreys K., Imyanitov E.N., Isaacs C., Jakimovska M., Jakubowska A., James P., Janavicius R., Jankowitz R.C., John E.M., Johnson N., Joseph V., Jung A., Karlan B.Y., Khusnutdinova E., Kiiski J.I., Konstantopoulou I., Kristensen V.N., Laitman Y., Lambrechts D., Lazaro C., Leroux D., Leslie G., Lester J., Lesueur F., Lindor N., Lindstrom S., Lo W.-Y., Loud J.T., Lubinski J., Makalic E., Mannermaa A., Manoochehri M., Manoukian S., Margolin S., Martens J.W.M., Martinez M.E., Matricardi L., Maurer T., Mavroudis D., McGuffog L., Meindl A., Menon U., Michailidou K., Kapoor P.M., Miller A., Montagna M., Moreno F., Moserle L., Mulligan A.M., Muranen T.A., Nathanson K.L., Neuhausen S.L., Nevanlinna H., Nevelsteen I., Nielsen F.C., Nikitina-Zake L., Offit K., Olah E., Olopade O.I., Olsson H., Osorio A., Papp J., Park-Simon T.-W., Parsons M.T., Pedersen I.S., and Peixoto A.
Abstract: Previous transcriptome-wide association studies (TWAS) have identified breast cancer risk genes by integrating data from expression quantitative loci and genome-wide association studies (GWAS), but analyses of breast cancer subtype-specific associations have been limited. In this study, we conducted a TWAS using gene expression data from GTEx and summary statistics from the hitherto largest GWAS meta-analysis conducted for breast cancer overall, and by estrogen receptor subtypes (ER+ and ER-). We further compared associations with ER+ and ER- subtypes, using a case-only TWAS approach. We also conducted multigene conditional analyses in regions with multiple TWAS associations. Two genes, STXBP4 and HIST2H2BA, were specifically associated with ER+ but not with ER- breast cancer. We further identified 30 TWAS-significant genes associated with overall breast cancer risk, including four that were not identified in previous studies. Conditional analyses identified single independent breast-cancer gene in three of six regions harboring multiple TWAS-significant genes. Our study provides new information on breast cancer genetics and biology, particularly about genomic differences between ER+ and ER- breast cancer.Copyright © 2020 The Authors. Genetic Epidemiology published by Wiley Periodicals, Inc.
Published: 2020

22. Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses.

Author: Goldgar D.E., Newman W.G., Nielsen F.C., Nikitina-Zake L., Nodora J., Offit K., Olah E., Olopade O.I., Olsson H., Orr N., Papi L., Papp J., Park-Simon T.-W., Parsons M.T., Peissel B., Peixoto A., Peshkin B., Peterlongo P., Peto J., Phillips K.-A., Piedmonte M., Plaseska-Karanfilska D., Prajzendanc K., Prentice R., Prokofyeva D., Rack B., Radice P., Ramus S.J., Rantala J., Rashid M.U., Rennert G., Rennert H.S., Risch H.A., Romero A., Rookus M.A., Rubner M., Rudiger T., Saloustros E., Sampson S., Sandler D.P., Sawyer E.J., Scheuner M.T., Schmutzler R.K., Schneeweiss A., Schoemaker M.J., Schottker B., Schurmann P., Senter L., Sharma P., Sherman M.E., Shu X.-O., Singer C.F., Smichkoska S., Soucy P., Southey M.C., Spinelli J.J., Stone J., Stoppa-Lyonnet D., Swerdlow A.J., Szabo C.I., Tamimi R.M., Tapper W.J., Taylor J.A., Teixeira M.R., Terry M.B., Thomassen M., Thull D.L., Tischkowitz M., Toland A.E., Tollenaar R.A.E.M., Tomlinson I., Torres D., Troester M.A., Truong T., Tung N., Untch M., Vachon C.M., van den Ouweland A.M.W., van der Kolk L.E., van Veen E.M., vanRensburg E.J., Vega A., Wappenschmidt B., Weinberg C.R., Weitzel J.N., Wildiers H., Winqvist R., Wolk A., Yang X.R., Yannoukakos D., Zheng W., Zorn K.K., Milne R.L., Kraft P., Simard J., Pharoah P.D.P., Michailidou K., Antoniou A.C., Schmidt M.K., Chenevix-Trench G., Easton D.F., Chatterjee N., Garcia-Closas M., Zhang H., Ahearn T.U., Lecarpentier J., Barnes D., Beesley J., Qi G., Jiang X., O'Mara T.A., Zhao N., Bolla M.K., Dunning A.M., Dennis J., Wang Q., Ful Z.A., Aittomaki K., Andrulis I.L., Anton-Culver H., Arndt V., Aronson K.J., Arun B.K., Auer P.L., Azzollini J., Barrowdale D., Becher H., Beckmann M.W., Behrens S., Benitez J., Bermisheva M., Bialkowska K., Blanco A., Blomqvist C., Bogdanova N.V., Bojesen S.E., Bonanni B., Bondavalli D., Borg A., Brauch H., Brenner H., Briceno I., Broeks A., Brucker S.Y., Bruning T., Burwinkel B., Buys S.S., Byers H., Caldes T., Caligo M.A., Calvello M., Campa D., Castelao J.E., Chang-Claude J., Chanock S.J., Christiaens M., Christiansen H., Chung W.K., Claes K.B.M., Clarke C.L., Cornelissen S., Couch F.J., Cox A., Cross S.S., Czene K., Daly M.B., Devilee P., Diez O., Domchek S.M., Dork T., Dwek M., Eccles D.M., Ekici A.B., Evans D.G., Fasching P.A., Figueroa J., Foretova L., Fostira F., Friedman E., Frost D., Gago-Dominguez M., Gapstur S.M., Garber J., Garcia-Saenz J.A., Gaudet M.M., Gayther S.A., Giles G.G., Godwin A.K., Goldberg M.S., Gonzalez-Neira A., Greene M.H., Gronwald J., Guenel P., Haberle L., Hahnen E., Haiman C.A., Hake C.R., Hall P., Hamann U., Harkness E.F., Heemskerk-Gerritsen B.A.M., Hillemanns P., Hogervorst F.B.L., Holleczek B., Hollestelle A., Hooning M.J., Hoover R.N., Hopper J.L., Howell A., Huebner H., Hulick P.J., Imyanitov E.N., Isaacs C., Izatt L., Jager A., Jakimovska M., Jakubowska A., James P., Janavicius R., Janni W., John E.M., Jones M.E., Jung A., Kaaks R., Kapoor P.M., Karlan B.Y., Keeman R., Khan S., Khusnutdinova E., Kitahara C.M., Ko Y.-D., Konstantopoulou I., Koppert L.B., Koutros S., Kristensen V.N., Laenkholm A.-V., Lambrechts D., Larsson S.C., Laurent-Puig P., Lazaro C., Lazarova E., Lejbkowicz F., Leslie G., Lesueur F., Lindblom A., Lissowska J., Lo W.-Y., Loud J.T., Lubinski J., Lukomska A., MacInnis R.J., Mannermaa A., Manoochehri M., Manoukian S., Margolin S., Martinez M.E., Matricardi L., McGuffog L., McLean C., Mebirouk N., Meindl A., Menon U., Miller A., Mingazheva E., Montagna M., Mulligan A.M., Mulot C., Muranen T.A., Nathanson K.L., Neuhausen S.L., Nevanlinna H., Neven P., Goldgar D.E., Newman W.G., Nielsen F.C., Nikitina-Zake L., Nodora J., Offit K., Olah E., Olopade O.I., Olsson H., Orr N., Papi L., Papp J., Park-Simon T.-W., Parsons M.T., Peissel B., Peixoto A., Peshkin B., Peterlongo P., Peto J., Phillips K.-A., Piedmonte M., Plaseska-Karanfilska D., Prajzendanc K., Prentice R., Prokofyeva D., Rack B., Radice P., Ramus S.J., Rantala J., Rashid M.U., Rennert G., Rennert H.S., Risch H.A., Romero A., Rookus M.A., Rubner M., Rudiger T., Saloustros E., Sampson S., Sandler D.P., Sawyer E.J., Scheuner M.T., Schmutzler R.K., Schneeweiss A., Schoemaker M.J., Schottker B., Schurmann P., Senter L., Sharma P., Sherman M.E., Shu X.-O., Singer C.F., Smichkoska S., Soucy P., Southey M.C., Spinelli J.J., Stone J., Stoppa-Lyonnet D., Swerdlow A.J., Szabo C.I., Tamimi R.M., Tapper W.J., Taylor J.A., Teixeira M.R., Terry M.B., Thomassen M., Thull D.L., Tischkowitz M., Toland A.E., Tollenaar R.A.E.M., Tomlinson I., Torres D., Troester M.A., Truong T., Tung N., Untch M., Vachon C.M., van den Ouweland A.M.W., van der Kolk L.E., van Veen E.M., vanRensburg E.J., Vega A., Wappenschmidt B., Weinberg C.R., Weitzel J.N., Wildiers H., Winqvist R., Wolk A., Yang X.R., Yannoukakos D., Zheng W., Zorn K.K., Milne R.L., Kraft P., Simard J., Pharoah P.D.P., Michailidou K., Antoniou A.C., Schmidt M.K., Chenevix-Trench G., Easton D.F., Chatterjee N., Garcia-Closas M., Zhang H., Ahearn T.U., Lecarpentier J., Barnes D., Beesley J., Qi G., Jiang X., O'Mara T.A., Zhao N., Bolla M.K., Dunning A.M., Dennis J., Wang Q., Ful Z.A., Aittomaki K., Andrulis I.L., Anton-Culver H., Arndt V., Aronson K.J., Arun B.K., Auer P.L., Azzollini J., Barrowdale D., Becher H., Beckmann M.W., Behrens S., Benitez J., Bermisheva M., Bialkowska K., Blanco A., Blomqvist C., Bogdanova N.V., Bojesen S.E., Bonanni B., Bondavalli D., Borg A., Brauch H., Brenner H., Briceno I., Broeks A., Brucker S.Y., Bruning T., Burwinkel B., Buys S.S., Byers H., Caldes T., Caligo M.A., Calvello M., Campa D., Castelao J.E., Chang-Claude J., Chanock S.J., Christiaens M., Christiansen H., Chung W.K., Claes K.B.M., Clarke C.L., Cornelissen S., Couch F.J., Cox A., Cross S.S., Czene K., Daly M.B., Devilee P., Diez O., Domchek S.M., Dork T., Dwek M., Eccles D.M., Ekici A.B., Evans D.G., Fasching P.A., Figueroa J., Foretova L., Fostira F., Friedman E., Frost D., Gago-Dominguez M., Gapstur S.M., Garber J., Garcia-Saenz J.A., Gaudet M.M., Gayther S.A., Giles G.G., Godwin A.K., Goldberg M.S., Gonzalez-Neira A., Greene M.H., Gronwald J., Guenel P., Haberle L., Hahnen E., Haiman C.A., Hake C.R., Hall P., Hamann U., Harkness E.F., Heemskerk-Gerritsen B.A.M., Hillemanns P., Hogervorst F.B.L., Holleczek B., Hollestelle A., Hooning M.J., Hoover R.N., Hopper J.L., Howell A., Huebner H., Hulick P.J., Imyanitov E.N., Isaacs C., Izatt L., Jager A., Jakimovska M., Jakubowska A., James P., Janavicius R., Janni W., John E.M., Jones M.E., Jung A., Kaaks R., Kapoor P.M., Karlan B.Y., Keeman R., Khan S., Khusnutdinova E., Kitahara C.M., Ko Y.-D., Konstantopoulou I., Koppert L.B., Koutros S., Kristensen V.N., Laenkholm A.-V., Lambrechts D., Larsson S.C., Laurent-Puig P., Lazaro C., Lazarova E., Lejbkowicz F., Leslie G., Lesueur F., Lindblom A., Lissowska J., Lo W.-Y., Loud J.T., Lubinski J., Lukomska A., MacInnis R.J., Mannermaa A., Manoochehri M., Manoukian S., Margolin S., Martinez M.E., Matricardi L., McGuffog L., McLean C., Mebirouk N., Meindl A., Menon U., Miller A., Mingazheva E., Montagna M., Mulligan A.M., Mulot C., Muranen T.A., Nathanson K.L., Neuhausen S.L., Nevanlinna H., and Neven P.
Abstract: Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype1-3. To identify novel loci, we performed a genome-wide association study including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. We identified 32 novel susceptibility loci (P < 5.0 x 10-8), 15 of which showed evidence for associations with at least one tumor feature (false discovery rate < 0.05). Five loci showed associations (P < 0.05) in opposite directions between luminal and non-luminal subtypes. In silico analyses showed that these five loci contained cell-specific enhancers that differed between normal luminal and basal mammary cells. The genetic correlations between five intrinsic-like subtypes ranged from 0.35 to 0.80. The proportion of genome-wide chip heritability explained by all known susceptibility loci was 54.2% for luminal A-like disease and 37.6% for triple-negative disease. The odds ratios of polygenic risk scores, which included 330 variants, for the highest 1% of quantiles compared with middle quantiles were 5.63 and 3.02 for luminal A-like and triple-negative disease, respectively. These findings provide an improved understanding of genetic predisposition to breast cancer subtypes and will inform the development of subtype-specific polygenic risk scores.Copyright © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.
Published: 2020

23. Transcriptome-wide association study of breast cancer risk by estrogen-receptor status

Author: Feng, H. (Helian), Gusev, A. (Alexander), Pasaniuc, B. (Bogdan), Wu, L. (Lang), Long, J. (Jirong), Abu-full, Z. (Zomoroda), Aittomäki, K. (Kristiina), Andrulis, I.L. (Irene L.), Anton-Culver, H. (Hoda), Antoniou, A.C. (Antonis C.), Arason, A. (Adalgeir), Arndt, V. (Volker), Aronson, K.J. (Kristan J.), Arun, B.K. (Banu), Asseryanis, E. (Ella), Auer, P.L. (Paul L.), Azzollini, J., Balmaña, J. (Judith), Barkardottir, R.B. (Rosa B.), Barnes, D. (Daniel), Barrowdale, D. (Daniel), Beckmann, M.W. (Matthias), Behrens, T.W. (Timothy), Benítez, J. (Javier), Bermisheva, M. (Marina), Białkowska, K. (Katarzyna), Blanco, A. (Ana), Blomqvist, C. (Carl), Boeckx, B. (Bram), Bogdanova, N.V. (Natalia V.), Bojesen, S.E. (Stig), Bolla, M.K. (Manjeet K.), Bonnani, B. (Bernardo), Borg, Å. (Åke), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Briceno, I. (Ignacio), Broeks, A. (Annegien), Brüning, T. (Thomas), Burwinkel, B. (Barbara), Cai, Q. (Qiuyin), Caldes, T. (Trinidad), Caligo, M.A. (Maria A.), Campbell, I. (Ian), Canisius, S. (Sander), Campa, D. (Daniele), Carter, B.D. (Brian D.), Carter, J. (Jonathan), Castelao, J.E. (Jose ), Chang-Claude, J. (Jenny), Chanock, S.J. (Stephen), Christiansen, H. (Hans), Chung, W. (Wendy), Claes, K.B.M. (Kathleen B. M.), Clarke, C. (Christine), Couch, F.J. (Fergus), Cox, A. (Angela), Cross, S.S. (Simon S.), Cybulski, C. (Cezary), Czene, K. (Kamila), Daly, M.B. (Mary), de la Hoya, M. (Miguel), De Leeneer, K. (Kim), Dennis, J. (Joe), Devilee, P. (Peter), Diez, O. (Orland), Domchek, S.M. (Susan), Dörk, T. (Thilo), Santos Silva, I. (Isabel) dos, Dunning, A.M. (Alison M.), Dwek, M. (Miriam), Eccles, D.M. (Diana M.), Ejlertsen, B. (Bent), Ellberg, C. (Carolina), Engel, C. (Christoph), Eriksson, M. (Mikael), Fasching, P.A. (Peter), Fletcher, O. (Olivia), Flyger, H. (Henrik), Fostira, F. (Florentia), Friedman, E. (Eitan), Fritschi, L. (Lin), Frost, D. (Debra), Gabrielson, M. (Marike), Ganz, P.A. (Patricia A.), Gapstur, S.M. (Susan M.), Garber, J. (Judy), García-Closas, M. (Montserrat), García-Sáenz, J.A. (José A.), Gaudet, M.M. (Mia M.), Giles, G.G. (Graham G.), Glendon, G. (Gord), Godwin, A.K. (Andrew), Goldberg, M.S. (Mark), Radice, P. (Paolo), González-Neira, A. (Anna), Greene, M.H. (Mark H.), Gronwald, J. (Jacek), Guénel, P. (Pascal), Haiman, C.A. (Christopher), Hall, P. (Per), Hamann, U. (Ute), Hake, C. (Christopher), He, W. (Wei), Heyworth, J. (Jane), Hogervorst, F.B.L. (Frans B.L.), Hollestelle, A. (Antoinette), Hooning, M.J. (Maartje J.), Hoover, R.N. (Robert), Hopper, J.L. (John), Huang, G. (Guanmengqian), Hulick, P.J. (Peter J.), Humphreys, K. (Keith), Imyanitov, E.N. (Evgeny), Isaacs, C. (Claudine), Jakimovska, M. (Milena), Jakubowska, A. (Anna), James, M. (Margaret), Janavicius, R. (Ramunas), Jankowitz, R.C. (Rachel C.), John, E.M. (Esther), Johnson, N. (Nichola), Joseph, V. (Vijai), Jung, A. (Audrey), Karlan, B.Y. (Beth), Khusnutdinova, E.K. (Elza), Kiiski, J.I. (Johanna I.), Konstantopoulou, I. (Irene), Kristensen, V. (Vessela), Laitman, Y. (Yael), Lambrechts, D. (Diether), Lázaro, C. (Conxi), Leroux, D. (Dominique), Leslie, G. (Goska), Lester, J. (Jenny), Lesueur, F. (Fabienne), Lindor, N.M. (Noralane), Lindström, S. (Sara), Lo, W.-Y. (Wing-Yee), Loud, J.T. (Jennifer T.), Lubinski, J. (Jan), Makalic, E. (Enes), Mannermaa, A. (Arto), Manoochehri, M. (Mehdi), Manoukian, S. (Siranoush), Margolin, S. (Sara), Martens, J.W.M. (John), Martinez, M.E. (Maria E.), Matricardi, L. (Laura), Maurer, T. (Tabea), Mavroudis, D. (Dimitris), McGuffog, L. (Lesley), Meindl, A. (Alfons), Menon, U. (Usha), Michailidou, K. (Kyriaki), Kapoor, P.M. (Pooja M.), Miller, A. (Austin), Montagna, M. (Marco), Moreno, F. (Fernando), Moserle, L. (Lidia), Mulligan, A.-M. (Anna-Marie), Muranen, T.A. (Taru A.), Nathanson, K.L. (Katherine), Floris, O.A.M., Nevanlinna, H. (Heli), Nevelsteen, I. (Ines), Nielsen, F. (Finn), Nikitina-Zake, L. (Liene), Offit, K. (Kenneth), Olah, E., Olopade, O.I. (Olofunmilayo), Olsson, H. (Håkan), Osorio, A. (Ana), Papp, J. (Janos), Park-Simon, T.-W. (Tjoung-Won), Parsons, M. (Marilyn), Pedersen, I.S. (Inge S.), Peixoto, A. (Ana), Peterlongo, P. (Paolo), Peto, J. (Julian), Pharoah, P.D.P. (Paul), Phillips, K.-A. (Kelly-Anne), Plaseska-Karanfilska, D. (Dijana), Poppe, B. (Bruce), Pradhan, N. (Nisha), Prajzendanc, K. (Karolina), Presneau, N. (Nadege), Punie, K. (Kevin), Pylkäs, K. (Katri), Rantala, J. (Johanna), Rashid, M.U. (Muhammad), Rennert, G. (Gad), Risch, H.A. (Harvey A.), Robson, M. (Mark), Romero, A. (Atocha), Saloustros, E. (Emmanouil), Sandler, D.P. (Dale P.), Santos, C. (Catarina), Sawyer, E.J. (Elinor), Schmidt, M.K. (Marjanka), Schmidt, D.F. (Daniel), Schmutzler, R.K. (Rita), Schoemaker, M.J. (Minouk J.), Scott, R.J. (Rodney), Sharma, P. (Priyanka), Shu, X.-O. (Xiao-Ou), Simard, J. (Jacques), Singer, C.F. (Christian), Skytte, A.-B. (Anne-Bine), Soucy, P. (Penny), Southey, M.C. (Melissa), Spinelli, J.J. (John J.), Spurdle, A.B. (Amanda), Stone, J. (Jennifer), Swerdlow, A.J. (Anthony ), Tapper, W.J. (William J.), Taylor, J.A. (Jack A.), Teixeira, P.J., Terry, M.B. (Mary Beth), Teulé, A. (Alex), Thomassen, M. (Mads), Thöne, K. (Kathrin), Thull, D.L. (Darcy L.), Tischkowitz, M. (Marc), Toland, A.E. (Amanda), Tollenaar, R.A.E.M. (Rob), Torres, D. (Diana), Truong, T. (Thérèse), Tung, N. (Nadine), Vachon, C. (Celine), van Asperen, C.J. (Christi J.), Ouweland, A.M.W. (Ans) van den, Rensburg, E.J. (Elizabeth) van, Vega, A. (Ana), Viel, A. (Alessandra), Vieiro-Balo, P. (Paula), Wang, Q. (Qin), Wappenschmidt, B. (Barbara), Weinberg, C.R. (Clarice R.), Weitzel, J.N. (Jeffrey), Wendt, C. (Camilla), Winqvist, R. (Robert), Yang, X.R. (Xiaohong R.), Yannoukakos, D. (Drakoulis), Ziogas, A. (Argyrios), Milne, R.L. (Roger), Adamo, P. (Pio) d', Chenevix-Trench, G. (Georgia), Zheng, W. (Wei), Kraft, P. (Peter), Jiang, X. (Xia), Feng, H. (Helian), Gusev, A. (Alexander), Pasaniuc, B. (Bogdan), Wu, L. (Lang), Long, J. (Jirong), Abu-full, Z. (Zomoroda), Aittomäki, K. (Kristiina), Andrulis, I.L. (Irene L.), Anton-Culver, H. (Hoda), Antoniou, A.C. (Antonis C.), Arason, A. (Adalgeir), Arndt, V. (Volker), Aronson, K.J. (Kristan J.), Arun, B.K. (Banu), Asseryanis, E. (Ella), Auer, P.L. (Paul L.), Azzollini, J., Balmaña, J. (Judith), Barkardottir, R.B. (Rosa B.), Barnes, D. (Daniel), Barrowdale, D. (Daniel), Beckmann, M.W. (Matthias), Behrens, T.W. (Timothy), Benítez, J. (Javier), Bermisheva, M. (Marina), Białkowska, K. (Katarzyna), Blanco, A. (Ana), Blomqvist, C. (Carl), Boeckx, B. (Bram), Bogdanova, N.V. (Natalia V.), Bojesen, S.E. (Stig), Bolla, M.K. (Manjeet K.), Bonnani, B. (Bernardo), Borg, Å. (Åke), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Briceno, I. (Ignacio), Broeks, A. (Annegien), Brüning, T. (Thomas), Burwinkel, B. (Barbara), Cai, Q. (Qiuyin), Caldes, T. (Trinidad), Caligo, M.A. (Maria A.), Campbell, I. (Ian), Canisius, S. (Sander), Campa, D. (Daniele), Carter, B.D. (Brian D.), Carter, J. (Jonathan), Castelao, J.E. (Jose ), Chang-Claude, J. (Jenny), Chanock, S.J. (Stephen), Christiansen, H. (Hans), Chung, W. (Wendy), Claes, K.B.M. (Kathleen B. M.), Clarke, C. (Christine), Couch, F.J. (Fergus), Cox, A. (Angela), Cross, S.S. (Simon S.), Cybulski, C. (Cezary), Czene, K. (Kamila), Daly, M.B. (Mary), de la Hoya, M. (Miguel), De Leeneer, K. (Kim), Dennis, J. (Joe), Devilee, P. (Peter), Diez, O. (Orland), Domchek, S.M. (Susan), Dörk, T. (Thilo), Santos Silva, I. (Isabel) dos, Dunning, A.M. (Alison M.), Dwek, M. (Miriam), Eccles, D.M. (Diana M.), Ejlertsen, B. (Bent), Ellberg, C. (Carolina), Engel, C. (Christoph), Eriksson, M. (Mikael), Fasching, P.A. (Peter), Fletcher, O. (Olivia), Flyger, H. (Henrik), Fostira, F. (Florentia), Friedman, E. (Eitan), Fritschi, L. (Lin), Frost, D. (Debra), Gabrielson, M. (Marike), Ganz, P.A. (Patricia A.), Gapstur, S.M. (Susan M.), Garber, J. (Judy), García-Closas, M. (Montserrat), García-Sáenz, J.A. (José A.), Gaudet, M.M. (Mia M.), Giles, G.G. (Graham G.), Glendon, G. (Gord), Godwin, A.K. (Andrew), Goldberg, M.S. (Mark), Radice, P. (Paolo), González-Neira, A. (Anna), Greene, M.H. (Mark H.), Gronwald, J. (Jacek), Guénel, P. (Pascal), Haiman, C.A. (Christopher), Hall, P. (Per), Hamann, U. (Ute), Hake, C. (Christopher), He, W. (Wei), Heyworth, J. (Jane), Hogervorst, F.B.L. (Frans B.L.), Hollestelle, A. (Antoinette), Hooning, M.J. (Maartje J.), Hoover, R.N. (Robert), Hopper, J.L. (John), Huang, G. (Guanmengqian), Hulick, P.J. (Peter J.), Humphreys, K. (Keith), Imyanitov, E.N. (Evgeny), Isaacs, C. (Claudine), Jakimovska, M. (Milena), Jakubowska, A. (Anna), James, M. (Margaret), Janavicius, R. (Ramunas), Jankowitz, R.C. (Rachel C.), John, E.M. (Esther), Johnson, N. (Nichola), Joseph, V. (Vijai), Jung, A. (Audrey), Karlan, B.Y. (Beth), Khusnutdinova, E.K. (Elza), Kiiski, J.I. (Johanna I.), Konstantopoulou, I. (Irene), Kristensen, V. (Vessela), Laitman, Y. (Yael), Lambrechts, D. (Diether), Lázaro, C. (Conxi), Leroux, D. (Dominique), Leslie, G. (Goska), Lester, J. (Jenny), Lesueur, F. (Fabienne), Lindor, N.M. (Noralane), Lindström, S. (Sara), Lo, W.-Y. (Wing-Yee), Loud, J.T. (Jennifer T.), Lubinski, J. (Jan), Makalic, E. (Enes), Mannermaa, A. (Arto), Manoochehri, M. (Mehdi), Manoukian, S. (Siranoush), Margolin, S. (Sara), Martens, J.W.M. (John), Martinez, M.E. (Maria E.), Matricardi, L. (Laura), Maurer, T. (Tabea), Mavroudis, D. (Dimitris), McGuffog, L. (Lesley), Meindl, A. (Alfons), Menon, U. (Usha), Michailidou, K. (Kyriaki), Kapoor, P.M. (Pooja M.), Miller, A. (Austin), Montagna, M. (Marco), Moreno, F. (Fernando), Moserle, L. (Lidia), Mulligan, A.-M. (Anna-Marie), Muranen, T.A. (Taru A.), Nathanson, K.L. (Katherine), Floris, O.A.M., Nevanlinna, H. (Heli), Nevelsteen, I. (Ines), Nielsen, F. (Finn), Nikitina-Zake, L. (Liene), Offit, K. (Kenneth), Olah, E., Olopade, O.I. (Olofunmilayo), Olsson, H. (Håkan), Osorio, A. (Ana), Papp, J. (Janos), Park-Simon, T.-W. (Tjoung-Won), Parsons, M. (Marilyn), Pedersen, I.S. (Inge S.), Peixoto, A. (Ana), Peterlongo, P. (Paolo), Peto, J. (Julian), Pharoah, P.D.P. (Paul), Phillips, K.-A. (Kelly-Anne), Plaseska-Karanfilska, D. (Dijana), Poppe, B. (Bruce), Pradhan, N. (Nisha), Prajzendanc, K. (Karolina), Presneau, N. (Nadege), Punie, K. (Kevin), Pylkäs, K. (Katri), Rantala, J. (Johanna), Rashid, M.U. (Muhammad), Rennert, G. (Gad), Risch, H.A. (Harvey A.), Robson, M. (Mark), Romero, A. (Atocha), Saloustros, E. (Emmanouil), Sandler, D.P. (Dale P.), Santos, C. (Catarina), Sawyer, E.J. (Elinor), Schmidt, M.K. (Marjanka), Schmidt, D.F. (Daniel), Schmutzler, R.K. (Rita), Schoemaker, M.J. (Minouk J.), Scott, R.J. (Rodney), Sharma, P. (Priyanka), Shu, X.-O. (Xiao-Ou), Simard, J. (Jacques), Singer, C.F. (Christian), Skytte, A.-B. (Anne-Bine), Soucy, P. (Penny), Southey, M.C. (Melissa), Spinelli, J.J. (John J.), Spurdle, A.B. (Amanda), Stone, J. (Jennifer), Swerdlow, A.J. (Anthony ), Tapper, W.J. (William J.), Taylor, J.A. (Jack A.), Teixeira, P.J., Terry, M.B. (Mary Beth), Teulé, A. (Alex), Thomassen, M. (Mads), Thöne, K. (Kathrin), Thull, D.L. (Darcy L.), Tischkowitz, M. (Marc), Toland, A.E. (Amanda), Tollenaar, R.A.E.M. (Rob), Torres, D. (Diana), Truong, T. (Thérèse), Tung, N. (Nadine), Vachon, C. (Celine), van Asperen, C.J. (Christi J.), Ouweland, A.M.W. (Ans) van den, Rensburg, E.J. (Elizabeth) van, Vega, A. (Ana), Viel, A. (Alessandra), Vieiro-Balo, P. (Paula), Wang, Q. (Qin), Wappenschmidt, B. (Barbara), Weinberg, C.R. (Clarice R.), Weitzel, J.N. (Jeffrey), Wendt, C. (Camilla), Winqvist, R. (Robert), Yang, X.R. (Xiaohong R.), Yannoukakos, D. (Drakoulis), Ziogas, A. (Argyrios), Milne, R.L. (Roger), Adamo, P. (Pio) d', Chenevix-Trench, G. (Georgia), Zheng, W. (Wei), Kraft, P. (Peter), and Jiang, X. (Xia)
Abstract: Previous transcriptome-wide association studies (TWAS) have identified breast cancer risk genes by integrating data from expression quantitative loci and genome-wide association studies (GWAS), but analyses of breast cancer subtype-specific associations have been limited. In this study, we conducted a TWAS using gene expression data from GTEx and summary statistics from the hitherto largest GWAS meta-analysis conducted for breast cancer overall, and by estrogen receptor subtypes (ER+ and ER−). We further compared associations with ER+ and ER− subtypes, using a case-only TWAS approach. We also conducted multigene conditional analyses in regions with multiple TWAS associations. Two genes, STXBP4 and HIST2H2BA, were specifically associated with ER+ but not with ER– breast cancer. We further identified 30 TWAS-significant genes associated with overall breast cancer risk, including four that were not identified in previous studies. Conditional analyses identified single independent breast-cancer gene in three of six regions harboring multiple TWAS-significant genes. Our study provides new information on breast cancer genetics and biology, particularly about genomic differences between ER+ and ER− breast cancer.
Published: 2020
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24. Shared heritability and functional enrichment across six solid cancers (vol 10, 431, 2019)

Author: Jiang, X., Finucane, H.K., Schumacher, F.R., Schmit, S.L., Tyrer, J.P., Han, Y., Michailidou, K., Lesseur, C., Kuchenbaecker, K.B., Dennis, J., Conti, D.V., Casey, G., Gaudet, M.M., Huyghe, J.R., Albanes, D., Aldrich, M.C., Andrew, A.S., Andrulis, I.L., Anton-Culver, H., Antoniou, A.C., Antonenkova, N.N., Arnold, S.M., Aronson, K.J., Arun, B.K., Bandera, E.V., Barkardottir, R.B., Barnes, D.R., Batra, J., Beckmann, M.W., Benitez, J., Benlloch, S., Berchuck, A., Berndt, S.I., Bickeboller, H., Bien, S.A., Blomqvist, C., Boccia, S., Bogdanova, N.V., Bojesen, S.E., Bolla, M.K., Brauch, H., Brenner, H., Brenton, J.D., Brook, M.N., Brunet, J., Brunnstrom, H., Buchanan, D.D., Burwinkel, B., Butzow, R., Cadoni, G., Caldes, T., Caligo, M.A., Campbell, I., Campbell, P.T., Cancel-Tassin, G., Cannon-Albright, L., Campa, D., Caporaso, N., Carvalho, A.L., Chan, A.T., Chang-Claude, J., Chanock, S.J., Chen, C., Christiani, D.C., Claes, K.B.M., Claessens, F., Clements, J., Collee, J.M., Correa, M.C., Couch, F.J., Cox, A., Cunningham, J.M., Cybulski, C., Czene, K., Daly, M.B., deFazio, A., Devilee, P., Diez, O., Gago-Dominguez, M., Donovan, J.L., Dork, T., Duell, E.J., Dunning, A.M., Dwek, M., Eccles, D.M., Edlund, C.K., Edwards, D.R.V., Ellberg, C., Evans, D.G., Fasching, P.A., Ferris, R.L., Liloglou, T., Figueiredo, J.C., Fletcher, O., Fortner, R.T., Fostira, F., Franceschi, S., Friedman, E., Gallinger, S.J., Ganz, P.A., Garber, J., Garcia-Saenz, J.A., Gayther, S.A., Giles, G.G., Godwin, A.K., Goldberg, M.S., Goldgar, D.E., Goode, E.L., Goodman, M.T., Goodman, G., Grankvist, K., Greene, M.H., Gronberg, H., Gronwald, J., Guenel, P., Hakansson, N., Hall, P., Hamann, U., Hamdy, F.C., Hamilton, R.J., Hampe, J., Haugen, A., Heitz, F., Herrero, R., Hillemanns, P., Hoffmeister, M., Hogdall, E., Hong, Y.C., Hopper, J.L., Houlston, R., Hulick, P.J., Hunter, D.J., Huntsman, D.G., Idos, G., Imyanitov, E.N., Ingles, S.A., Isaacs, C., Jakubowska, A., James, P., Jenkins, M.A., Johansson, M., John, E.M., Joshi, A.D., Kaneva, R., Karlan, B.Y., Kelemen, L.E., Kuhl, T., Khaw, K.T., Khusnutdinova, E., Kibel, A.S., Kiemeney, L.A., Kim, J., Kjaer, S.K., Knight, J.A., Kogevinas, M., Kote-Jarai, Z., Koutros, S., Kristensen, V.N., Kupryjanczyk, J., Lacko, M., Lam, S., Lambrechts, D., Landi, M.T., Lazarus, P., N.D. le, Lee, E., Lejbkowicz, F., Lenz, H.J., Leslie, G., Lessel, D., Lester, J., Levine, D.A., Li, L., Li, C.I., Lindblom, A., Lindor, N.M., Liu, G., Loupakis, F., Lubinski, J., Maehle, L., Maier, C., Mannermaa, A., Marchand, L., Margolin, S., May, T., McGuffog, L., Meindl, A., Middha, P., Miller, A., Milne, R.L., MacInnis, R.J., Modugno, F., Montagna, M., Moreno, V., Moysich, K.B., Mucci, L., Muir, K., Mulligan, A.M., Nathanson, K.L., Neal, D.E., Ness, A.R., Neuhausen, S.L., Nevanlinna, H., Newcomb, P.A., Newcomb, L.F., Nielsen, F.C., Nikitina-Zake, L., Nordestgaard, B.G., Nussbaum, R.L., Offit, K., Olah, E., Olama, A.A. al, Olopade, O.I., Olshan, A.F., Olsson, H., Osorio, A., Pandha, H., Park, J.Y., Pashayan, N., Parsons, M.T., Pejovic, T., Penney, K.L., Peters, W.H.M., Phelan, C.M., Phipps, A.I., Plaseska-Karanfilska, D., Pring, M., Prokofyeva, D., Radice, P., Stefansson, K., Ramus, S.J., Raskin, L., Rennert, G., Rennert, H.S., Rensburg, E.J., Riggan, M.J., Risch, H.A., Risch, A., Roobol, M.J., Rosenstein, B.S., Rossing, M.A., Ruyck, K., Saloustros, E., Sandler, D.P., Sawyer, E.J., Schabath, M.B., Schleutker, J., Schmidt, M.K., Setiawan, V.W., Shen, H.B., Siegel, E.M., Sieh, W., Singer, C.F., Slattery, M.L., Sorensen, K.D., Southey, M.C., Spurdle, A.B., Stanford, J.L., Stevens, V.L., Stintzing, S., Stone, J., Sundfeldt, K., Sutphen, R., Swerdlow, A.J., Tajara, E.H., Tangen, C.M., Tardon, A., Taylor, J.A., Teare, M.D., Teixeira, M.R., Terry, M.B., Terry, K.L., Thibodeau, S.N., Thomassen, M., Bjorge, L., Tischkowitz, M., Toland, A.E., Torres, D., Townsend, P.A., Travis, R.C., Tung, N., and Tworoger
Published: 2019

25. Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers

Author: Qian, F., Rookus, Matti A., Leslie, G., Risch, H.A., Greene, M.H., Aalfs, C.M., Adank, M.A., Adlard, J., Agnarsson, B.A., Ahmed, M., Aittomaki, K., Andrulis, I.L., Arnold, N., Arun, B.K., Ausems, M., Azzollini, J., Barrowdale, D., Barwell, J., Benitez, J., Bialkowska, K., Bonadona, V., Borde, J., Borg, A., Bradbury, A.R., Brunet, J., Buys, S.S., Caldes, T., Caligo, M.A., Campbell, I., Carter, J., Chiquette, J., Chung, W.K., Claes, K.B.M., Collee, J.M., Collonge-Rame, M.A., Couch, F.J., Daly, M.B., Delnatte, C., Diez, O., Domchek, S.M., Dorfling, C.M., Eason, J., Easton, D.F., Eeles, R., Engel, C., Evans, D.G., Faivre, L., Feliubadalo, L., Foretova, L., Friedman, E., Frost, D., Ganz, P.A., Garber, J., Garcia-Barberan, V., Gehrig, A., Glendon, G., Godwin, A.K., Garcia, E.B., Hamann, U., Hauke, J., Hopper, J.L., Hulick, P.J., Imyanitov, E.N., Isaacs, C., Izatt, L., Jakubowska, A., Janavicius, R., John, E.M., Karlan, B.Y., Kets, C.M., Laitman, Y., Lazaro, C., Leroux, D., Lester, J., Lesueur, F., Loud, J.T., Lubinski, J., Lukomska, A., McGuffog, L., Mebirouk, N., Meijers-Heijboer, H.E., Meindl, A., Miller, A., Montagna, M., Mooij, T.M., Mouret-Fourme, E., Nathanson, K.L., Nehoray, B., Neuhausen, S.L., Nevanlinna, H., Nielsen, F.C., Offit, K., Olah, E., Ong, K.R., Oosterwijk, J.C, Ottini, L., Parsons, M.T., Peterlongo, P., Pfeiler, G., Pradhan, N., et al., Qian, F., Rookus, Matti A., Leslie, G., Risch, H.A., Greene, M.H., Aalfs, C.M., Adank, M.A., Adlard, J., Agnarsson, B.A., Ahmed, M., Aittomaki, K., Andrulis, I.L., Arnold, N., Arun, B.K., Ausems, M., Azzollini, J., Barrowdale, D., Barwell, J., Benitez, J., Bialkowska, K., Bonadona, V., Borde, J., Borg, A., Bradbury, A.R., Brunet, J., Buys, S.S., Caldes, T., Caligo, M.A., Campbell, I., Carter, J., Chiquette, J., Chung, W.K., Claes, K.B.M., Collee, J.M., Collonge-Rame, M.A., Couch, F.J., Daly, M.B., Delnatte, C., Diez, O., Domchek, S.M., Dorfling, C.M., Eason, J., Easton, D.F., Eeles, R., Engel, C., Evans, D.G., Faivre, L., Feliubadalo, L., Foretova, L., Friedman, E., Frost, D., Ganz, P.A., Garber, J., Garcia-Barberan, V., Gehrig, A., Glendon, G., Godwin, A.K., Garcia, E.B., Hamann, U., Hauke, J., Hopper, J.L., Hulick, P.J., Imyanitov, E.N., Isaacs, C., Izatt, L., Jakubowska, A., Janavicius, R., John, E.M., Karlan, B.Y., Kets, C.M., Laitman, Y., Lazaro, C., Leroux, D., Lester, J., Lesueur, F., Loud, J.T., Lubinski, J., Lukomska, A., McGuffog, L., Mebirouk, N., Meijers-Heijboer, H.E., Meindl, A., Miller, A., Montagna, M., Mooij, T.M., Mouret-Fourme, E., Nathanson, K.L., Nehoray, B., Neuhausen, S.L., Nevanlinna, H., Nielsen, F.C., Offit, K., Olah, E., Ong, K.R., Oosterwijk, J.C, Ottini, L., Parsons, M.T., Peterlongo, P., Pfeiler, G., and Pradhan, N., et al.
Abstract: Contains fulltext : 208524.pdf (publisher's version ) (Open Access), BACKGROUND: Height and body mass index (BMI) are associated with higher ovarian cancer risk in the general population, but whether such associations exist among BRCA1/2 mutation carriers is unknown. METHODS: We applied a Mendelian randomisation approach to examine height/BMI with ovarian cancer risk using the Consortium of Investigators for the Modifiers of BRCA1/2 (CIMBA) data set, comprising 14,676 BRCA1 and 7912 BRCA2 mutation carriers, with 2923 ovarian cancer cases. We created a height genetic score (height-GS) using 586 height-associated variants and a BMI genetic score (BMI-GS) using 93 BMI-associated variants. Associations were assessed using weighted Cox models. RESULTS: Observed height was not associated with ovarian cancer risk (hazard ratio [HR]: 1.07 per 10-cm increase in height, 95% confidence interval [CI]: 0.94-1.23). Height-GS showed similar results (HR = 1.02, 95% CI: 0.85-1.23). Higher BMI was significantly associated with increased risk in premenopausal women with HR = 1.25 (95% CI: 1.06-1.48) and HR = 1.59 (95% CI: 1.08-2.33) per 5-kg/m(2) increase in observed and genetically determined BMI, respectively. No association was found for postmenopausal women. Interaction between menopausal status and BMI was significant (Pinteraction < 0.05). CONCLUSION: Our observation of a positive association between BMI and ovarian cancer risk in premenopausal BRCA1/2 mutation carriers is consistent with findings in the general population.
Published: 2019

26. The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer.

Author: Boutry-Kryza N., Rantala J., Rashid M.U., Rau-Murthy R., Rennert G., Lejbkowicz F., Rhenius V., Romero A., Rookus M.A., Ross E.A., Rossing M., Rudaitis V., Ruebner M., Saloustros E., Sanden K., Santamarina M., Scheuner M.T., Schmutzler R.K., Schneider M., Scott C., Senter L., Shah M., Sharma P., Shu X.-O., Simard J., Singer C.F., Sohn C., Soucy P., Southey M.C., Spinelli J.J., Steele L., Stoppa-Lyonnet D., Tapper W.J., Teixeira M.R., Terry M.B., Thomassen M., Thompson J., Thull D.L., Tischkowitz M., Tollenaar R.A.E.M., Torres D., Troester M.A., Truong T., Tung N., Untch M., Vachon C.M., van Rensburg E.J., van Veen E.M., Vega A., Viel A., Wappenschmidt B., Weitzel J.N., Wendt C., Wieme G., Wolk A., Yang X.R., Zheng W., Ziogas A., Zorn K.K., Dunning A.M., Lush M., Wang Q., McGuffog L., Parsons M.T., Pharoah P.D.P., Fostira F., Toland A.E., Andrulis I.L., Ramus S.J., Swerdlow A.J., Greene M.H., Chung W.K., Milne R.L., Chenevix-Trench G., Dork T., Schmidt M.K., Easton D.F., Radice P., Hahnen E., Antoniou A.C., Couch F.J., Nevanlinna H., Surralles J., Peterlongo P., Harris M., Figlioli G., Bogliolo M., Catucci I., Caleca L., Lasheras S.V., Pujol R., Kiiski J.I., Muranen T.A., Barnes D.R., Dennis J., Michailidou K., Bolla M.K., Leslie G., Aalfs C.M., Balleine R., Baxter R., Braye S., Carpenter J., Dahlstrom J., Forbes J., Lee C.S., Marsh D., Morey A., Pathmanathan N., Scott R., Simpson P., Spigelman A., Wilcken N., Yip D., Zeps N., Adank M.A., Adlard J., Agata S., Cadoo K., Agnarsson B.A., Ahearn T., Aittomaki K., Ambrosone C.B., Andrews L., Anton-Culver H., Antonenkova N.N., Arndt V., Arnold N., Aronson K.J., Arun B.K., Asseryanis E., Auber B., Auvinen P., Azzollini J., Balmana J., Barkardottir R.B., Barrowdale D., Barwell J., Beane Freeman L.E., Beauparlant C.J., Beckmann M.W., Behrens S., Benitez J., Berger R., Bermisheva M., Blanco A.M., Blomqvist C., Bogdanova N.V., Bojesen A., Bojesen S.E., Bonanni B., Borg A., Brady A.F., Brauch H., Brenner H., Bruning T., Burwinkel B., Buys S.S., Caldes T., Caliebe A., Caligo M.A., Campa D., Campbell I.G., Canzian F., Castelao J.E., Chang-Claude J., Chanock S.J., Claes K.B.M., Clarke C.L., Collavoli A., Conner T.A., Cox D.G., Cybulski C., Czene K., Daly M.B., de la Hoya M., Devilee P., Diez O., Ding Y.C., Dite G.S., Ditsch N., Domchek S.M., Dorfling C.M., dos-Santos-Silva I., Durda K., Dwek M., Eccles D.M., Ekici A.B., Eliassen A.H., Ellberg C., Eriksson M., Evans D.G., Fasching P.A., Figueroa J., Flyger H., Foulkes W.D., Friebel T.M., Friedman E., Gabrielson M., Gaddam P., Gago-Dominguez M., Gao C., Gapstur S.M., Garber J., Garcia-Closas M., Garcia-Saenz J.A., Gaudet M.M., Gayther S.A., Belotti M., Bertrand O., Birot A.-M., Buecher B., Caputo S., Dupre A., Fourme E., Gauthier-Villars M., Golmard L., Le Mentec M., Moncoutier V., de Pauw A., Saule C., Calender A., Giraud S., Leone M., Bressac-de-Paillerets B., Caron O., Guillaud-Bataille M., Bignon Y.-J., Uhrhammer N., Bonadona V., Lasset C., Berthet P., Castera L., Vaur D., Bourdon V., Nogues C., Noguchi T., Popovici C., Remenieras A., Sobol H., Coupier I., Pujol P., Adenis C., Dumont A., Revillion F., Muller D., Barouk-Simonet E., Bonnet F., Bubien V., Longy M., Sevenet N., Gladieff L., Guimbaud R., Feillel V., Toulas C., Dreyfus H., Leroux C.D., Peysselon M., Rebischung C., Legrand C., Baurand A., Bertolone G., Coron F., Faivre L., Jacquot C., Lizard S., Kientz C., Lebrun M., Prieur F., Fert-Ferrer S., Mari V., Venat-Bouvet L., Bezieau S., Delnatte C., Mortemousque I., Colas C., Coulet F., Soubrier F., Warcoin M., Bronner M., Sokolowska J., Collonge-Rame M.-A., Damette A., Gesta P., Lallaoui H., Chiesa J., Molina-Gomes D., Ingster O., Manouvrier-Hanu S., Lejeune S., Giles G.G., Glendon G., Godwin A.K., Goldberg M.S., Goldgar D.E., Guenel P., Gutierrez-Barrera A.M., Haeberle L., Haiman C.A., Hakansson N., Hall P., Hamann U., Harrington P.A., Hein A., Heyworth J., Hillemanns P., Hollestelle A., Hopper J.L., Hosgood H.D., Howell A., Hu C., Hulick P.J., Hunter D.J., Imyanitov E.N., Aghmesheh M., Greening S., Amor D., Gattas M., Botes L., Buckley M., Friedlander M., Koehler J., Meiser B., Saleh M., Salisbury E., Trainer A., Tucker K., Antill Y., Dobrovic A., Fellows A., Fox S., Nightingale S., Phillips K., Sambrook J., Thorne H., Armitage S., Arnold L., Kefford R., Kirk J., Rickard E., Bastick P., Beesley J., Hayward N., Spurdle A., Walker L., Beilby J., Saunders C., Bennett I., Blackburn A., Bogwitz M., Gaff C., Lindeman G., Pachter N., Sexton A., Visvader J., Taylor J., Winship I., Brennan M., Brown M., French J., Edwards S., Burgess M., Burke J., Patterson B., Butow P., Culling B., Caldon L., Callen D., Chauhan D., Eisenbruch M., Heiniger L., Chauhan M., Christian A., Dixon J., Kidd A., Cohen P., Colley A., Fenton G., Crook A., Dickson R., Field M., Cui J., Cummings M., Dawson S.-J., DeFazio A., Delatycki M., Dudding T., Edkins T., Farshid G., Flanagan J., Fong P., Forrest L., Gallego-Ortega D., George P., Gill G., Kollias J., Haan E., Hart S., Jenkins M., Hunt C., Lakhani S., Lipton L., Lobb L., Mann G., McLachlan S.A., O'Connell S., O'Sullivan S., Pieper E., Robinson B., Saunus J., Scott E., Shelling A., Williams R., Young M.A., Isaacs C., Jakimovska M., Jakubowska A., James P., Janavicius R., Janni W., John E.M., Jones M.E., Jung A., Kaaks R., Karlan B.Y., Khusnutdinova E., Kitahara C.M., Konstantopoulou I., Koutros S., Kraft P., Lambrechts D., Lazaro C., Le Marchand L., Lester J., Lesueur F., Lilyquist J., Loud J.T., Lu K.H., Luben R.N., Lubinski J., Mannermaa A., Manoochehri M., Manoukian S., Margolin S., Martens J.W.M., Maurer T., Mavroudis D., Mebirouk N., Meindl A., Menon U., Miller A., Montagna M., Nathanson K.L., Neuhausen S.L., Newman W.G., Nguyen-Dumont T., Nielsen F.C., Nielsen S., Nikitina-Zake L., Offit K., Olah E., Olopade O.I., Olshan A.F., Olson J.E., Olsson H., Osorio A., Ottini L., Peissel B., Peixoto A., Peto J., Plaseska-Karanfilska D., Pocza T., Presneau N., Pujana M.A., Punie K., Rack B., Boutry-Kryza N., Rantala J., Rashid M.U., Rau-Murthy R., Rennert G., Lejbkowicz F., Rhenius V., Romero A., Rookus M.A., Ross E.A., Rossing M., Rudaitis V., Ruebner M., Saloustros E., Sanden K., Santamarina M., Scheuner M.T., Schmutzler R.K., Schneider M., Scott C., Senter L., Shah M., Sharma P., Shu X.-O., Simard J., Singer C.F., Sohn C., Soucy P., Southey M.C., Spinelli J.J., Steele L., Stoppa-Lyonnet D., Tapper W.J., Teixeira M.R., Terry M.B., Thomassen M., Thompson J., Thull D.L., Tischkowitz M., Tollenaar R.A.E.M., Torres D., Troester M.A., Truong T., Tung N., Untch M., Vachon C.M., van Rensburg E.J., van Veen E.M., Vega A., Viel A., Wappenschmidt B., Weitzel J.N., Wendt C., Wieme G., Wolk A., Yang X.R., Zheng W., Ziogas A., Zorn K.K., Dunning A.M., Lush M., Wang Q., McGuffog L., Parsons M.T., Pharoah P.D.P., Fostira F., Toland A.E., Andrulis I.L., Ramus S.J., Swerdlow A.J., Greene M.H., Chung W.K., Milne R.L., Chenevix-Trench G., Dork T., Schmidt M.K., Easton D.F., Radice P., Hahnen E., Antoniou A.C., Couch F.J., Nevanlinna H., Surralles J., Peterlongo P., Harris M., Figlioli G., Bogliolo M., Catucci I., Caleca L., Lasheras S.V., Pujol R., Kiiski J.I., Muranen T.A., Barnes D.R., Dennis J., Michailidou K., Bolla M.K., Leslie G., Aalfs C.M., Balleine R., Baxter R., Braye S., Carpenter J., Dahlstrom J., Forbes J., Lee C.S., Marsh D., Morey A., Pathmanathan N., Scott R., Simpson P., Spigelman A., Wilcken N., Yip D., Zeps N., Adank M.A., Adlard J., Agata S., Cadoo K., Agnarsson B.A., Ahearn T., Aittomaki K., Ambrosone C.B., Andrews L., Anton-Culver H., Antonenkova N.N., Arndt V., Arnold N., Aronson K.J., Arun B.K., Asseryanis E., Auber B., Auvinen P., Azzollini J., Balmana J., Barkardottir R.B., Barrowdale D., Barwell J., Beane Freeman L.E., Beauparlant C.J., Beckmann M.W., Behrens S., Benitez J., Berger R., Bermisheva M., Blanco A.M., Blomqvist C., Bogdanova N.V., Bojesen A., Bojesen S.E., Bonanni B., Borg A., Brady A.F., Brauch H., Brenner H., Bruning T., Burwinkel B., Buys S.S., Caldes T., Caliebe A., Caligo M.A., Campa D., Campbell I.G., Canzian F., Castelao J.E., Chang-Claude J., Chanock S.J., Claes K.B.M., Clarke C.L., Collavoli A., Conner T.A., Cox D.G., Cybulski C., Czene K., Daly M.B., de la Hoya M., Devilee P., Diez O., Ding Y.C., Dite G.S., Ditsch N., Domchek S.M., Dorfling C.M., dos-Santos-Silva I., Durda K., Dwek M., Eccles D.M., Ekici A.B., Eliassen A.H., Ellberg C., Eriksson M., Evans D.G., Fasching P.A., Figueroa J., Flyger H., Foulkes W.D., Friebel T.M., Friedman E., Gabrielson M., Gaddam P., Gago-Dominguez M., Gao C., Gapstur S.M., Garber J., Garcia-Closas M., Garcia-Saenz J.A., Gaudet M.M., Gayther S.A., Belotti M., Bertrand O., Birot A.-M., Buecher B., Caputo S., Dupre A., Fourme E., Gauthier-Villars M., Golmard L., Le Mentec M., Moncoutier V., de Pauw A., Saule C., Calender A., Giraud S., Leone M., Bressac-de-Paillerets B., Caron O., Guillaud-Bataille M., Bignon Y.-J., Uhrhammer N., Bonadona V., Lasset C., Berthet P., Castera L., Vaur D., Bourdon V., Nogues C., Noguchi T., Popovici C., Remenieras A., Sobol H., Coupier I., Pujol P., Adenis C., Dumont A., Revillion F., Muller D., Barouk-Simonet E., Bonnet F., Bubien V., Longy M., Sevenet N., Gladieff L., Guimbaud R., Feillel V., Toulas C., Dreyfus H., Leroux C.D., Peysselon M., Rebischung C., Legrand C., Baurand A., Bertolone G., Coron F., Faivre L., Jacquot C., Lizard S., Kientz C., Lebrun M., Prieur F., Fert-Ferrer S., Mari V., Venat-Bouvet L., Bezieau S., Delnatte C., Mortemousque I., Colas C., Coulet F., Soubrier F., Warcoin M., Bronner M., Sokolowska J., Collonge-Rame M.-A., Damette A., Gesta P., Lallaoui H., Chiesa J., Molina-Gomes D., Ingster O., Manouvrier-Hanu S., Lejeune S., Giles G.G., Glendon G., Godwin A.K., Goldberg M.S., Goldgar D.E., Guenel P., Gutierrez-Barrera A.M., Haeberle L., Haiman C.A., Hakansson N., Hall P., Hamann U., Harrington P.A., Hein A., Heyworth J., Hillemanns P., Hollestelle A., Hopper J.L., Hosgood H.D., Howell A., Hu C., Hulick P.J., Hunter D.J., Imyanitov E.N., Aghmesheh M., Greening S., Amor D., Gattas M., Botes L., Buckley M., Friedlander M., Koehler J., Meiser B., Saleh M., Salisbury E., Trainer A., Tucker K., Antill Y., Dobrovic A., Fellows A., Fox S., Nightingale S., Phillips K., Sambrook J., Thorne H., Armitage S., Arnold L., Kefford R., Kirk J., Rickard E., Bastick P., Beesley J., Hayward N., Spurdle A., Walker L., Beilby J., Saunders C., Bennett I., Blackburn A., Bogwitz M., Gaff C., Lindeman G., Pachter N., Sexton A., Visvader J., Taylor J., Winship I., Brennan M., Brown M., French J., Edwards S., Burgess M., Burke J., Patterson B., Butow P., Culling B., Caldon L., Callen D., Chauhan D., Eisenbruch M., Heiniger L., Chauhan M., Christian A., Dixon J., Kidd A., Cohen P., Colley A., Fenton G., Crook A., Dickson R., Field M., Cui J., Cummings M., Dawson S.-J., DeFazio A., Delatycki M., Dudding T., Edkins T., Farshid G., Flanagan J., Fong P., Forrest L., Gallego-Ortega D., George P., Gill G., Kollias J., Haan E., Hart S., Jenkins M., Hunt C., Lakhani S., Lipton L., Lobb L., Mann G., McLachlan S.A., O'Connell S., O'Sullivan S., Pieper E., Robinson B., Saunus J., Scott E., Shelling A., Williams R., Young M.A., Isaacs C., Jakimovska M., Jakubowska A., James P., Janavicius R., Janni W., John E.M., Jones M.E., Jung A., Kaaks R., Karlan B.Y., Khusnutdinova E., Kitahara C.M., Konstantopoulou I., Koutros S., Kraft P., Lambrechts D., Lazaro C., Le Marchand L., Lester J., Lesueur F., Lilyquist J., Loud J.T., Lu K.H., Luben R.N., Lubinski J., Mannermaa A., Manoochehri M., Manoukian S., Margolin S., Martens J.W.M., Maurer T., Mavroudis D., Mebirouk N., Meindl A., Menon U., Miller A., Montagna M., Nathanson K.L., Neuhausen S.L., Newman W.G., Nguyen-Dumont T., Nielsen F.C., Nielsen S., Nikitina-Zake L., Offit K., Olah E., Olopade O.I., Olshan A.F., Olson J.E., Olsson H., Osorio A., Ottini L., Peissel B., Peixoto A., Peto J., Plaseska-Karanfilska D., Pocza T., Presneau N., Pujana M.A., Punie K., and Rack B.
Abstract: Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM-/- patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors.Copyright © 2019, The Author(s).
Published: 2019

27. Shared heritability and functional enrichment across six solid cancers.

Author: Fletcher O., Tardon A., Taylor J.A., Teare M.D., Teixeira M.R., Terry M.B., Terry K.L., Thibodeau S.N., Thomassen M., Bjorge L., Tischkowitz M., Toland A.E., Torres D., Townsend P.A., Travis R.C., Tung N., Tworoger S.S., Ulrich C.M., Usmani N., Vachon C.M., Van Nieuwenhuysen E., Vega A., Aguado-Barrera M.E., Wang Q., Webb P.M., Weinberg C.R., Weinstein S., Weissler M.C., Weitzel J.N., West C.M.L., White E., Whittemore A.S., Wichmann H.-E., Wiklund F., Winqvist R., Wolk A., Woll P., Woods M., Wu A.H., Wu X., Yannoukakos D., Zheng W., Zienolddiny S., Ziogas A., Zorn K.K., Lane J.M., Saxena R., Thomas D., Hung R.J., Diergaarde B., McKay J., Peters U., Hsu L., Garcia-Closas M., Eeles R.A., Chenevix-Trench G., Brennan P.J., Haiman C.A., Simard J., Easton D.F., Gruber S.B., Pharoah P.D.P., Price A.L., Pasaniuc B., Amos C.I., Kraft P., Lindstrom S., Chen C., Anton-Culver H., Antoniou A.C., Antonenkova N.N., Arnold S.M., Jiang X., Finucane H.K., Schumacher F.R., Schmit S.L., Tyrer J.P., Han Y., Michailidou K., Lesseur C., Kuchenbaecker K.B., Dennis J., Conti D.V., Casey G., Gaudet M.M., Huyghe J.R., Albanes D., Aldrich M.C., Andrew A.S., Andrulis I.L., Aronson K.J., Arun B.K., Bandera E.V., Barkardottir R.B., Barnes D.R., Batra J., Beckmann M.W., Benitez J., Benlloch S., Berchuck A., Berndt S.I., Bickeboller H., Bien S.A., Blomqvist C., Boccia S., Bogdanova N.V., Bojesen S.E., Bolla M.K., Brauch H., Brenner H., Brenton J.D., Brook M.N., Brunet J., Brunnstrom H., Buchanan D.D., Burwinkel B., Butzow R., Cadoni G., Caldes T., Caligo M.A., Campbell I., Campbell P.T., Cancel-Tassin G., Cannon-Albright L., Campa D., Caporaso N., Carvalho A.L., Chan A.T., Chang-Claude J., Chanock S.J., Christiani D.C., Claes K.B.M., Claessens F., Clements J., Collee J.M., Correa M.C., Couch F.J., Cox A., Cunningham J.M., Cybulski C., Czene K., Daly M.B., deFazio A., Devilee P., Diez O., Gago-Dominguez M., Donovan J.L., Dork T., Duell E.J., Dunning A.M., Dwek M., Eccles D.M., Edlund C.K., Edwards D.R.V., Ellberg C., Evans D.G., Fasching P.A., Ferris R.L., Liloglou T., Figueiredo J.C., Fortner R.T., Fostira F., Franceschi S., Friedman E., Gallinger S.J., Ganz P.A., Garber J., Garcia-Saenz J.A., Gayther S.A., Giles G.G., Godwin A.K., Goldberg M.S., Goldgar D.E., Goode E.L., Goodman M.T., Goodman G., Grankvist K., Greene M.H., Gronberg H., Gronwald J., Guenel P., Hakansson N., Hall P., Hamann U., Hamdy F.C., Hamilton R.J., Hampe J., Haugen A., Heitz F., Herrero R., Hillemanns P., Hoffmeister M., Hogdall E., Hong Y.-C., Hopper J.L., Houlston R., Hulick P.J., Hunter D.J., Huntsman D.G., Idos G., Imyanitov E.N., Ingles S.A., Isaacs C., Jakubowska A., James P., Jenkins M.A., Johansson M., John E.M., Joshi A.D., Kaneva R., Karlan B.Y., Kelemen L.E., Kuhl T., Khaw K.-T., Khusnutdinova E., Kibel A.S., Kiemeney L.A., Kim J., Kjaer S.K., Knight J.A., Kogevinas M., Kote-Jarai Z., Koutros S., Kristensen V.N., Kupryjanczyk J., Lacko M., Lam S., Lambrechts D., Landi M.T., Lazarus P., Le N.D., Lee E., Lejbkowicz F., Lenz H.-J., Leslie G., Lessel D., Lester J., Levine D.A., Li L., Li C.I., Lindblom A., Lindor N.M., Liu G., Loupakis F., Lubinski J., Maehle L., Maier C., Mannermaa A., Marchand L.L., Margolin S., May T., McGuffog L., Meindl A., Middha P., Miller A., Milne R.L., MacInnis R.J., Modugno F., Montagna M., Moreno V., Moysich K.B., Mucci L., Muir K., Mulligan A.M., Nathanson K.L., Neal D.E., Ness A.R., Neuhausen S.L., Nevanlinna H., Newcomb P.A., Newcomb L.F., Nielsen F.C., Nikitina-Zake L., Nordestgaard B.G., Nussbaum R.L., Offit K., Olah E., Olama A.A.A., Olopade O.I., Olshan A.F., Olsson H., Osorio A., Pandha H., Park J.Y., Pashayan N., Parsons M.T., Pejovic T., Penney K.L., Peters W.H.M., Phelan C.M., Phipps A.I., Plaseska-Karanfilska D., Pring M., Prokofyeva D., Radice P., Stefansson K., Ramus S.J., Raskin L., Rennert G., Rennert H.S., van Rensburg E.J., Riggan M.J., Risch H.A., Risch A., Roobol M.J., Rosenstein B.S., Rossing M.A., De Ruyck K., Saloustros E., Sandler D.P., Sawyer E.J., Schabath M.B., Schleutker J., Schmidt M.K., Setiawan V.W., Shen H., Siegel E.M., Sieh W., Singer C.F., Slattery M.L., Sorensen K.D., Southey M.C., Spurdle A.B., Stanford J.L., Stevens V.L., Stintzing S., Stone J., Sundfeldt K., Sutphen R., Swerdlow A.J., Tajara E.H., Tangen C.M., Fletcher O., Tardon A., Taylor J.A., Teare M.D., Teixeira M.R., Terry M.B., Terry K.L., Thibodeau S.N., Thomassen M., Bjorge L., Tischkowitz M., Toland A.E., Torres D., Townsend P.A., Travis R.C., Tung N., Tworoger S.S., Ulrich C.M., Usmani N., Vachon C.M., Van Nieuwenhuysen E., Vega A., Aguado-Barrera M.E., Wang Q., Webb P.M., Weinberg C.R., Weinstein S., Weissler M.C., Weitzel J.N., West C.M.L., White E., Whittemore A.S., Wichmann H.-E., Wiklund F., Winqvist R., Wolk A., Woll P., Woods M., Wu A.H., Wu X., Yannoukakos D., Zheng W., Zienolddiny S., Ziogas A., Zorn K.K., Lane J.M., Saxena R., Thomas D., Hung R.J., Diergaarde B., McKay J., Peters U., Hsu L., Garcia-Closas M., Eeles R.A., Chenevix-Trench G., Brennan P.J., Haiman C.A., Simard J., Easton D.F., Gruber S.B., Pharoah P.D.P., Price A.L., Pasaniuc B., Amos C.I., Kraft P., Lindstrom S., Chen C., Anton-Culver H., Antoniou A.C., Antonenkova N.N., Arnold S.M., Jiang X., Finucane H.K., Schumacher F.R., Schmit S.L., Tyrer J.P., Han Y., Michailidou K., Lesseur C., Kuchenbaecker K.B., Dennis J., Conti D.V., Casey G., Gaudet M.M., Huyghe J.R., Albanes D., Aldrich M.C., Andrew A.S., Andrulis I.L., Aronson K.J., Arun B.K., Bandera E.V., Barkardottir R.B., Barnes D.R., Batra J., Beckmann M.W., Benitez J., Benlloch S., Berchuck A., Berndt S.I., Bickeboller H., Bien S.A., Blomqvist C., Boccia S., Bogdanova N.V., Bojesen S.E., Bolla M.K., Brauch H., Brenner H., Brenton J.D., Brook M.N., Brunet J., Brunnstrom H., Buchanan D.D., Burwinkel B., Butzow R., Cadoni G., Caldes T., Caligo M.A., Campbell I., Campbell P.T., Cancel-Tassin G., Cannon-Albright L., Campa D., Caporaso N., Carvalho A.L., Chan A.T., Chang-Claude J., Chanock S.J., Christiani D.C., Claes K.B.M., Claessens F., Clements J., Collee J.M., Correa M.C., Couch F.J., Cox A., Cunningham J.M., Cybulski C., Czene K., Daly M.B., deFazio A., Devilee P., Diez O., Gago-Dominguez M., Donovan J.L., Dork T., Duell E.J., Dunning A.M., Dwek M., Eccles D.M., Edlund C.K., Edwards D.R.V., Ellberg C., Evans D.G., Fasching P.A., Ferris R.L., Liloglou T., Figueiredo J.C., Fortner R.T., Fostira F., Franceschi S., Friedman E., Gallinger S.J., Ganz P.A., Garber J., Garcia-Saenz J.A., Gayther S.A., Giles G.G., Godwin A.K., Goldberg M.S., Goldgar D.E., Goode E.L., Goodman M.T., Goodman G., Grankvist K., Greene M.H., Gronberg H., Gronwald J., Guenel P., Hakansson N., Hall P., Hamann U., Hamdy F.C., Hamilton R.J., Hampe J., Haugen A., Heitz F., Herrero R., Hillemanns P., Hoffmeister M., Hogdall E., Hong Y.-C., Hopper J.L., Houlston R., Hulick P.J., Hunter D.J., Huntsman D.G., Idos G., Imyanitov E.N., Ingles S.A., Isaacs C., Jakubowska A., James P., Jenkins M.A., Johansson M., John E.M., Joshi A.D., Kaneva R., Karlan B.Y., Kelemen L.E., Kuhl T., Khaw K.-T., Khusnutdinova E., Kibel A.S., Kiemeney L.A., Kim J., Kjaer S.K., Knight J.A., Kogevinas M., Kote-Jarai Z., Koutros S., Kristensen V.N., Kupryjanczyk J., Lacko M., Lam S., Lambrechts D., Landi M.T., Lazarus P., Le N.D., Lee E., Lejbkowicz F., Lenz H.-J., Leslie G., Lessel D., Lester J., Levine D.A., Li L., Li C.I., Lindblom A., Lindor N.M., Liu G., Loupakis F., Lubinski J., Maehle L., Maier C., Mannermaa A., Marchand L.L., Margolin S., May T., McGuffog L., Meindl A., Middha P., Miller A., Milne R.L., MacInnis R.J., Modugno F., Montagna M., Moreno V., Moysich K.B., Mucci L., Muir K., Mulligan A.M., Nathanson K.L., Neal D.E., Ness A.R., Neuhausen S.L., Nevanlinna H., Newcomb P.A., Newcomb L.F., Nielsen F.C., Nikitina-Zake L., Nordestgaard B.G., Nussbaum R.L., Offit K., Olah E., Olama A.A.A., Olopade O.I., Olshan A.F., Olsson H., Osorio A., Pandha H., Park J.Y., Pashayan N., Parsons M.T., Pejovic T., Penney K.L., Peters W.H.M., Phelan C.M., Phipps A.I., Plaseska-Karanfilska D., Pring M., Prokofyeva D., Radice P., Stefansson K., Ramus S.J., Raskin L., Rennert G., Rennert H.S., van Rensburg E.J., Riggan M.J., Risch H.A., Risch A., Roobol M.J., Rosenstein B.S., Rossing M.A., De Ruyck K., Saloustros E., Sandler D.P., Sawyer E.J., Schabath M.B., Schleutker J., Schmidt M.K., Setiawan V.W., Shen H., Siegel E.M., Sieh W., Singer C.F., Slattery M.L., Sorensen K.D., Southey M.C., Spurdle A.B., Stanford J.L., Stevens V.L., Stintzing S., Stone J., Sundfeldt K., Sutphen R., Swerdlow A.J., Tajara E.H., and Tangen C.M.
Abstract: Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (rg = 0.57, p = 4.6 x 10-8), breast and ovarian cancer (rg = 0.24, p = 7 x 10-5), breast and lung cancer (rg = 0.18, p =1.5 x 10-6) and breast and colorectal cancer (rg = 0.15, p = 1.1 x 10-4). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.Copyright © 2019, The Author(s).
Published: 2019

28. Publisher Correction: Shared heritability and functional enrichment across six solid cancers (Nature Communications, (2019), 10, 1, (431), 10.1038/s41467-018-08054-4).

Author: Tangen C.M., Wu X., Yannoukakos D., Zheng W., Zienolddiny S., Ziogas A., Zorn K.K., Lane J.M., Saxena R., Thomas D., Hung R.J., Diergaarde B., McKay J., Peters U., Hsu L., Garcia-Closas M., Eeles R.A., Chenevix-Trench G., Brennan P.J., Haiman C.A., Simard J., Easton D.F., Gruber S.B., Pharoah P.D.P., Price A.L., Pasaniuc B., Amos C.I., Kraft P., Lindstrom S., Chen C., Jiang X., Finucane H.K., Schumacher F.R., Schmit S.L., Tyrer J.P., Han Y., Michailidou K., Lesseur C., Kuchenbaecker K.B., Dennis J., Conti D.V., Casey G., Gaudet M.M., Huyghe J.R., Albanes D., Aldrich M.C., Andrew A.S., Andrulis I.L., Anton-Culver H., Antoniou A.C., Antonenkova N.N., Arnold S.M., Aronson K.J., Arun B.K., Bandera E.V., Barkardottir R.B., Barnes D.R., Batra J., Beckmann M.W., Benitez J., Benlloch S., Berchuck A., Berndt S.I., Bickeboller H., Bien S.A., Blomqvist C., Boccia S., Bogdanova N.V., Bojesen S.E., Bolla M.K., Brauch H., Brenner H., Brenton J.D., Brook M.N., Brunet J., Brunnstrom H., Buchanan D.D., Burwinkel B., Butzow R., Cadoni G., Caldes T., Caligo M.A., Campbell I., Campbell P.T., Cancel-Tassin G., Cannon-Albright L., Campa D., Caporaso N., Carvalho A.L., Chan A.T., Chang-Claude J., Chanock S.J., Christiani D.C., Claes K.B.M., Claessens F., Clements J., Collee J.M., Correa M.C., Couch F.J., Cox A., Cunningham J.M., Cybulski C., Czene K., Daly M.B., deFazio A., Devilee P., Diez O., Gago-Dominguez M., Donovan J.L., Dork T., Duell E.J., Dunning A.M., Dwek M., Eccles D.M., Edlund C.K., Edwards D.R.V., Ellberg C., Evans D.G., Fasching P.A., Ferris R.L., Liloglou T., Figueiredo J.C., Fletcher O., Fortner R.T., Fostira F., Franceschi S., Friedman E., Gallinger S.J., Ganz P.A., Garber J., Garcia-Saenz J.A., Gayther S.A., Giles G.G., Godwin A.K., Goldberg M.S., Goldgar D.E., Goode E.L., Goodman M.T., Goodman G., Grankvist K., Greene M.H., Gronberg H., Gronwald J., Guenel P., Hakansson N., Hall P., Hamann U., Hamdy F.C., Hamilton R.J., Hampe J., Haugen A., Heitz F., Herrero R., Hillemanns P., Hoffmeister M., Hogdall E., Hong Y.-C., Hopper J.L., Houlston R., Hulick P.J., Hunter D.J., Huntsman D.G., Idos G., Imyanitov E.N., Ingles S.A., Isaacs C., Jakubowska A., James P., Jenkins M.A., Johansson M., John E.M., Joshi A.D., Kaneva R., Karlan B.Y., Kelemen L.E., Kuhl T., Khaw K.-T., Khusnutdinova E., Kibel A.S., Kiemeney L.A., Kim J., Kjaer S.K., Knight J.A., Kogevinas M., Kote-Jarai Z., Koutros S., Kristensen V.N., Kupryjanczyk J., Lacko M., Lam S., Lambrechts D., Landi M.T., Lazarus P., Le N.D., Lee E., Lejbkowicz F., Lenz H.-J., Leslie G., Lessel D., Lester J., Levine D.A., Li L., Li C.I., Lindblom A., Lindor N.M., Liu G., Loupakis F., Lubinski J., Maehle L., Maier C., Mannermaa A., Marchand L.L., Margolin S., May T., McGuffog L., Meindl A., Middha P., Miller A., Milne R.L., MacInnis R.J., Modugno F., Montagna M., Moreno V., Moysich K.B., Mucci L., Muir K., Mulligan A.M., Nathanson K.L., Neal D.E., Ness A.R., Neuhausen S.L., Nevanlinna H., Newcomb P.A., Newcomb L.F., Nielsen F.C., Nikitina-Zake L., Nordestgaard B.G., Nussbaum R.L., Offit K., Olah E., Olama A.A.A., Olopade O.I., Olshan A.F., Olsson H., Osorio A., Pandha H., Park J.Y., Pashayan N., Parsons M.T., Pejovic T., Penney K.L., Peters W.H.M., Phelan C.M., Phipps A.I., Plaseska-Karanfilska D., Pring M., Prokofyeva D., Radice P., Stefansson K., Ramus S.J., Raskin L., Rennert G., Rennert H.S., van Rensburg E.J., Riggan M.J., Risch H.A., Risch A., Roobol M.J., Rosenstein B.S., Rossing M.A., De Ruyck K., Saloustros E., Sandler D.P., Sawyer E.J., Schabath M.B., Schleutker J., Schmidt M.K., Setiawan V.W., Shen H., Siegel E.M., Sieh W., Singer C.F., Slattery M.L., Sorensen K.D., Southey M.C., Spurdle A.B., Stanford J.L., Stevens V.L., Stintzing S., Stone J., Sundfeldt K., Sutphen R., Swerdlow A.J., Tajara E.H., Tardon A., Taylor J.A., Teare M.D., Teixeira M.R., Terry M.B., Terry K.L., Thibodeau S.N., Thomassen M., Bjorge L., Tischkowitz M., Toland A.E., Torres D., Townsend P.A., Travis R.C., Tung N., Tworoger S.S., Ulrich C.M., Usmani N., Vachon C.M., Van Nieuwenhuysen E., Vega A., Aguado-Barrera M.E., Wang Q., Webb P.M., Weinberg C.R., Weinstein S., Weissler M.C., Weitzel J.N., West C.M.L., White E., Whittemore A.S., Wichmann H.-E., Wiklund F., Winqvist R., Wolk A., Woll P., Woods M., Wu A.H., Tangen C.M., Wu X., Yannoukakos D., Zheng W., Zienolddiny S., Ziogas A., Zorn K.K., Lane J.M., Saxena R., Thomas D., Hung R.J., Diergaarde B., McKay J., Peters U., Hsu L., Garcia-Closas M., Eeles R.A., Chenevix-Trench G., Brennan P.J., Haiman C.A., Simard J., Easton D.F., Gruber S.B., Pharoah P.D.P., Price A.L., Pasaniuc B., Amos C.I., Kraft P., Lindstrom S., Chen C., Jiang X., Finucane H.K., Schumacher F.R., Schmit S.L., Tyrer J.P., Han Y., Michailidou K., Lesseur C., Kuchenbaecker K.B., Dennis J., Conti D.V., Casey G., Gaudet M.M., Huyghe J.R., Albanes D., Aldrich M.C., Andrew A.S., Andrulis I.L., Anton-Culver H., Antoniou A.C., Antonenkova N.N., Arnold S.M., Aronson K.J., Arun B.K., Bandera E.V., Barkardottir R.B., Barnes D.R., Batra J., Beckmann M.W., Benitez J., Benlloch S., Berchuck A., Berndt S.I., Bickeboller H., Bien S.A., Blomqvist C., Boccia S., Bogdanova N.V., Bojesen S.E., Bolla M.K., Brauch H., Brenner H., Brenton J.D., Brook M.N., Brunet J., Brunnstrom H., Buchanan D.D., Burwinkel B., Butzow R., Cadoni G., Caldes T., Caligo M.A., Campbell I., Campbell P.T., Cancel-Tassin G., Cannon-Albright L., Campa D., Caporaso N., Carvalho A.L., Chan A.T., Chang-Claude J., Chanock S.J., Christiani D.C., Claes K.B.M., Claessens F., Clements J., Collee J.M., Correa M.C., Couch F.J., Cox A., Cunningham J.M., Cybulski C., Czene K., Daly M.B., deFazio A., Devilee P., Diez O., Gago-Dominguez M., Donovan J.L., Dork T., Duell E.J., Dunning A.M., Dwek M., Eccles D.M., Edlund C.K., Edwards D.R.V., Ellberg C., Evans D.G., Fasching P.A., Ferris R.L., Liloglou T., Figueiredo J.C., Fletcher O., Fortner R.T., Fostira F., Franceschi S., Friedman E., Gallinger S.J., Ganz P.A., Garber J., Garcia-Saenz J.A., Gayther S.A., Giles G.G., Godwin A.K., Goldberg M.S., Goldgar D.E., Goode E.L., Goodman M.T., Goodman G., Grankvist K., Greene M.H., Gronberg H., Gronwald J., Guenel P., Hakansson N., Hall P., Hamann U., Hamdy F.C., Hamilton R.J., Hampe J., Haugen A., Heitz F., Herrero R., Hillemanns P., Hoffmeister M., Hogdall E., Hong Y.-C., Hopper J.L., Houlston R., Hulick P.J., Hunter D.J., Huntsman D.G., Idos G., Imyanitov E.N., Ingles S.A., Isaacs C., Jakubowska A., James P., Jenkins M.A., Johansson M., John E.M., Joshi A.D., Kaneva R., Karlan B.Y., Kelemen L.E., Kuhl T., Khaw K.-T., Khusnutdinova E., Kibel A.S., Kiemeney L.A., Kim J., Kjaer S.K., Knight J.A., Kogevinas M., Kote-Jarai Z., Koutros S., Kristensen V.N., Kupryjanczyk J., Lacko M., Lam S., Lambrechts D., Landi M.T., Lazarus P., Le N.D., Lee E., Lejbkowicz F., Lenz H.-J., Leslie G., Lessel D., Lester J., Levine D.A., Li L., Li C.I., Lindblom A., Lindor N.M., Liu G., Loupakis F., Lubinski J., Maehle L., Maier C., Mannermaa A., Marchand L.L., Margolin S., May T., McGuffog L., Meindl A., Middha P., Miller A., Milne R.L., MacInnis R.J., Modugno F., Montagna M., Moreno V., Moysich K.B., Mucci L., Muir K., Mulligan A.M., Nathanson K.L., Neal D.E., Ness A.R., Neuhausen S.L., Nevanlinna H., Newcomb P.A., Newcomb L.F., Nielsen F.C., Nikitina-Zake L., Nordestgaard B.G., Nussbaum R.L., Offit K., Olah E., Olama A.A.A., Olopade O.I., Olshan A.F., Olsson H., Osorio A., Pandha H., Park J.Y., Pashayan N., Parsons M.T., Pejovic T., Penney K.L., Peters W.H.M., Phelan C.M., Phipps A.I., Plaseska-Karanfilska D., Pring M., Prokofyeva D., Radice P., Stefansson K., Ramus S.J., Raskin L., Rennert G., Rennert H.S., van Rensburg E.J., Riggan M.J., Risch H.A., Risch A., Roobol M.J., Rosenstein B.S., Rossing M.A., De Ruyck K., Saloustros E., Sandler D.P., Sawyer E.J., Schabath M.B., Schleutker J., Schmidt M.K., Setiawan V.W., Shen H., Siegel E.M., Sieh W., Singer C.F., Slattery M.L., Sorensen K.D., Southey M.C., Spurdle A.B., Stanford J.L., Stevens V.L., Stintzing S., Stone J., Sundfeldt K., Sutphen R., Swerdlow A.J., Tajara E.H., Tardon A., Taylor J.A., Teare M.D., Teixeira M.R., Terry M.B., Terry K.L., Thibodeau S.N., Thomassen M., Bjorge L., Tischkowitz M., Toland A.E., Torres D., Townsend P.A., Travis R.C., Tung N., Tworoger S.S., Ulrich C.M., Usmani N., Vachon C.M., Van Nieuwenhuysen E., Vega A., Aguado-Barrera M.E., Wang Q., Webb P.M., Weinberg C.R., Weinstein S., Weissler M.C., Weitzel J.N., West C.M.L., White E., Whittemore A.S., Wichmann H.-E., Wiklund F., Winqvist R., Wolk A., Woll P., Woods M., and Wu A.H.
Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.Copyright © 2019, The Author(s).
Published: 2019

29. Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer.

Author: Herold N., Rantala J., Rennert G., Risch H.A., Saloustros E., Sanden K., Sawyer E.J., Schmidt M.K., Schmutzler R.K., Sharma P., Shu X.-O., Simard J., Singer C.F., Soucy P., Southey M.C., Spinelli J.J., Spurdle A.B., Stone J., Swerdlow A.J., Tapper W.J., Taylor J.A., Teixeira M.R., Terry M.B., Teule A., Thomassen M., Thone K., Thull D.L., Tischkowitz M., Toland A.E., Torres D., Truong T., Tung N., Vachon C.M., van Asperen C.J., van den Ouweland A.M.W., van Rensburg E.J., Vega A., Viel A., Wang Q., Wappenschmidt B., Weitzel J.N., Wendt C., Winqvist R., Yang X.R., Yannoukakos D., Ziogas A., Kraft P., Antoniou A.C., Zheng W., Easton D.F., Milne R.L., Beesley J., Chenevix-Trench G., Ferreira M.A., Gamazon E.R., Al-Ejeh F., Aittomaki K., Andrulis I.L., Anton-Culver H., Arason A., Arndt V., Aronson K.J., Arun B.K., Asseryanis E., Azzollini J., Balmana J., Barnes D.R., Barrowdale D., Beckmann M.W., Behrens S., Benitez J., Bermisheva M., Bialkowska K., Blomqvist C., Bogdanova N.V., Bojesen S.E., Bolla M.K., Borg A., Brauch H., Brenner H., Broeks A., Burwinkel B., Caldes T., Caligo M.A., Campa D., Campbell I., Canzian F., Carter J., Carter B.D., Castelao J.E., Chang-Claude J., Chanock S.J., Christiansen H., Chung W.K., Claes K.B.M., Clarke C.L., Adlard J., Ahmed M., Barwell J., Brady A., Brewer C., Cook J., Davidson R., Donaldson A., Eason J., Eeles R., Evans D.G., Gregory H., Hanson H., Henderson A., Hodgson S., Izatt L., Kennedy M.J., Lalloo F., Miller C., Morrison P.J., Ong K.-R., Perkins J., Porteous M.E., Rogers M.T., Side L.E., Snape K., Walker L., Harrington P.A., Arnold N., Auber B., Bogdanova-Markov N., Borde J., Caliebe A., Ditsch N., Dworniczak B., Engert S., Faust U., Gehrig A., Hahnen E., Hauke J., Hentschel J., Honisch E., Just W., Kast K., Larsen M., Lemke J., Nguyen H.P., Niederacher D., Ott C.-E., Platzer K., Pohl-Rescigno E., Ramser J., Rhiem K., Steinemann D., Sutter C., Varon-Mateeva R., Wang-Gohrke S., Weber B.H.F., Prieur F., Pujol P., Sagne C., Sevenet N., Sobol H., Sokolowska J., Stoppa-Lyonnet D., Venat-Bouvet L., Couch F.J., Cox A., Cross S.S., Czene K., Daly M.B., de la Hoya M., Dennis J., Devilee P., Diez O., Dork T., Dunning A.M., Dwek M., Eccles D.M., Ejlertsen B., Ellberg C., Engel C., Eriksson M., Fasching P.A., Fletcher O., Flyger H., Friedman E., Frost D., Gabrielson M., Gago-Dominguez M., Ganz P.A., Gapstur S.M., Garber J., Garcia-Closas M., Garcia-Saenz J.A., Gaudet M.M., Giles G.G., Glendon G., Godwin A.K., Goldberg M.S., Goldgar D.E., Gonzalez-Neira A., Greene M.H., Gronwald J., Guenel P., Haiman C.A., Hall P., Hamann U., He W., Heyworth J., Hogervorst F.B.L., Hollestelle A., Hoover R.N., Hopper J.L., Hulick P.J., Humphreys K., Imyanitov E.N., Balleine R., Baxter R., Braye S., Carpenter J., Dahlstrom J., Forbes J., Lee S.C., Marsh D., Morey A., Pathmanathan N., Simpson P., Spigelman A., Wilcken N., Yip D., Heemskerk-Gerritsen B.A.M., Rookus M.A., Seynaeve C.M., van der Baan F.H., van der Hout A.H., van der Kolk L.E., van der Luijt R.B., van Deurzen C.H.M., van Doorn H.C., van Engelen K., van Hest L., van Os T.A.M., Verhoef S., Vogel M.J., Wijnen J.T., Miron A., Kapuscinski M., Bane A., Ross E., Buys S.S., Conner T.A., Isaacs C., Jakimovska M., Jakubowska A., James P.A., Janavicius R., Jankowitz R.C., John E.M., Johnson N., Joseph V., Karlan B.Y., Khusnutdinova E., Kiiski J.I., Ko Y.-D., Jones M.E., Konstantopoulou I., Kristensen V.N., Laitman Y., Lambrechts D., Lazaro C., Leslie G., Lester J., Lesueur F., Lindstrom S., Long J., Loud J.T., Lubinski J., Makalic E., Mannermaa A., Manoochehri M., Margolin S., Maurer T., Mavroudis D., McGuffog L., Meindl A., Menon U., Michailidou K., Miller A., Montagna M., Moreno F., Moserle L., Mulligan A.M., Nathanson K.L., Neuhausen S.L., Nevanlinna H., Nevelsteen I., Nielsen F.C., Nikitina-Zake L., Nussbaum R.L., Offit K., Olah E., Olopade O.I., Olsson H., Osorio A., Papp J., Park-Simon T.-W., Parsons M.T., Pedersen I.S., Peixoto A., Peterlongo P., Pharoah P.D.P., Plaseska-Karanfilska D., Poppe B., Presneau N., Radice P., Herold N., Rantala J., Rennert G., Risch H.A., Saloustros E., Sanden K., Sawyer E.J., Schmidt M.K., Schmutzler R.K., Sharma P., Shu X.-O., Simard J., Singer C.F., Soucy P., Southey M.C., Spinelli J.J., Spurdle A.B., Stone J., Swerdlow A.J., Tapper W.J., Taylor J.A., Teixeira M.R., Terry M.B., Teule A., Thomassen M., Thone K., Thull D.L., Tischkowitz M., Toland A.E., Torres D., Truong T., Tung N., Vachon C.M., van Asperen C.J., van den Ouweland A.M.W., van Rensburg E.J., Vega A., Viel A., Wang Q., Wappenschmidt B., Weitzel J.N., Wendt C., Winqvist R., Yang X.R., Yannoukakos D., Ziogas A., Kraft P., Antoniou A.C., Zheng W., Easton D.F., Milne R.L., Beesley J., Chenevix-Trench G., Ferreira M.A., Gamazon E.R., Al-Ejeh F., Aittomaki K., Andrulis I.L., Anton-Culver H., Arason A., Arndt V., Aronson K.J., Arun B.K., Asseryanis E., Azzollini J., Balmana J., Barnes D.R., Barrowdale D., Beckmann M.W., Behrens S., Benitez J., Bermisheva M., Bialkowska K., Blomqvist C., Bogdanova N.V., Bojesen S.E., Bolla M.K., Borg A., Brauch H., Brenner H., Broeks A., Burwinkel B., Caldes T., Caligo M.A., Campa D., Campbell I., Canzian F., Carter J., Carter B.D., Castelao J.E., Chang-Claude J., Chanock S.J., Christiansen H., Chung W.K., Claes K.B.M., Clarke C.L., Adlard J., Ahmed M., Barwell J., Brady A., Brewer C., Cook J., Davidson R., Donaldson A., Eason J., Eeles R., Evans D.G., Gregory H., Hanson H., Henderson A., Hodgson S., Izatt L., Kennedy M.J., Lalloo F., Miller C., Morrison P.J., Ong K.-R., Perkins J., Porteous M.E., Rogers M.T., Side L.E., Snape K., Walker L., Harrington P.A., Arnold N., Auber B., Bogdanova-Markov N., Borde J., Caliebe A., Ditsch N., Dworniczak B., Engert S., Faust U., Gehrig A., Hahnen E., Hauke J., Hentschel J., Honisch E., Just W., Kast K., Larsen M., Lemke J., Nguyen H.P., Niederacher D., Ott C.-E., Platzer K., Pohl-Rescigno E., Ramser J., Rhiem K., Steinemann D., Sutter C., Varon-Mateeva R., Wang-Gohrke S., Weber B.H.F., Prieur F., Pujol P., Sagne C., Sevenet N., Sobol H., Sokolowska J., Stoppa-Lyonnet D., Venat-Bouvet L., Couch F.J., Cox A., Cross S.S., Czene K., Daly M.B., de la Hoya M., Dennis J., Devilee P., Diez O., Dork T., Dunning A.M., Dwek M., Eccles D.M., Ejlertsen B., Ellberg C., Engel C., Eriksson M., Fasching P.A., Fletcher O., Flyger H., Friedman E., Frost D., Gabrielson M., Gago-Dominguez M., Ganz P.A., Gapstur S.M., Garber J., Garcia-Closas M., Garcia-Saenz J.A., Gaudet M.M., Giles G.G., Glendon G., Godwin A.K., Goldberg M.S., Goldgar D.E., Gonzalez-Neira A., Greene M.H., Gronwald J., Guenel P., Haiman C.A., Hall P., Hamann U., He W., Heyworth J., Hogervorst F.B.L., Hollestelle A., Hoover R.N., Hopper J.L., Hulick P.J., Humphreys K., Imyanitov E.N., Balleine R., Baxter R., Braye S., Carpenter J., Dahlstrom J., Forbes J., Lee S.C., Marsh D., Morey A., Pathmanathan N., Simpson P., Spigelman A., Wilcken N., Yip D., Heemskerk-Gerritsen B.A.M., Rookus M.A., Seynaeve C.M., van der Baan F.H., van der Hout A.H., van der Kolk L.E., van der Luijt R.B., van Deurzen C.H.M., van Doorn H.C., van Engelen K., van Hest L., van Os T.A.M., Verhoef S., Vogel M.J., Wijnen J.T., Miron A., Kapuscinski M., Bane A., Ross E., Buys S.S., Conner T.A., Isaacs C., Jakimovska M., Jakubowska A., James P.A., Janavicius R., Jankowitz R.C., John E.M., Johnson N., Joseph V., Karlan B.Y., Khusnutdinova E., Kiiski J.I., Ko Y.-D., Jones M.E., Konstantopoulou I., Kristensen V.N., Laitman Y., Lambrechts D., Lazaro C., Leslie G., Lester J., Lesueur F., Lindstrom S., Long J., Loud J.T., Lubinski J., Makalic E., Mannermaa A., Manoochehri M., Margolin S., Maurer T., Mavroudis D., McGuffog L., Meindl A., Menon U., Michailidou K., Miller A., Montagna M., Moreno F., Moserle L., Mulligan A.M., Nathanson K.L., Neuhausen S.L., Nevanlinna H., Nevelsteen I., Nielsen F.C., Nikitina-Zake L., Nussbaum R.L., Offit K., Olah E., Olopade O.I., Olsson H., Osorio A., Papp J., Park-Simon T.-W., Parsons M.T., Pedersen I.S., Peixoto A., Peterlongo P., Pharoah P.D.P., Plaseska-Karanfilska D., Poppe B., Presneau N., and Radice P.
Abstract: Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.Copyright © 2019, The Author(s).
Published: 2019

30. Erratum: Publisher Correction: Shared heritability and functional enrichment across six solid cancers (Nature communications (2019) 10 1 (431))

Author: Jiang, X. (Xia), Finucane, H.K. (Hilary K.), Schumacher, F.R. (Fredrick R), Schmit, S.L. (Stephanie L.), Tyrer, J.P. (Jonathan P.), Han, Y. (Younghun), Michailidou, K. (Kyriaki), Lesseur, C. (Corina), Kuchenbaecker, K.B. (Karoline), Dennis, J. (Joe), Conti, G. (Giario), Casey, G. (Graham), Gaudet, M.M. (Mia M.), Huyghe, J.R. (Jeroen R.), Albanes, D. (Demetrius), Aldrich, M.C. (Melinda), Andrew, A.S. (Angeline S.), Andrulis, I.L. (Irene L.), Anton-Culver, H. (Hoda), Antoniou, A.C. (Antonis C.), Antonenkova, N.N. (Natalia N.), Arnold, S.M. (Susanne M.), Aronson, K.J. (Kristan J.), Arun, B.K. (Banu), Bandera, E.V. (Elisa), Barkardottir, R.B. (Rosa B.), Barnes, D. (Daniel), Batra, J. (Jyotsna), Beckmann, M.W. (Matthias), Benítez, J. (Javier), Benlloch, S. (Sara), Berchuck, A. (Andrew), Berndt, S.I. (Sonja), Bickeböller, H. (Heike), Bien, S.A. (Stephanie A.), Blomqvist, C. (Carl), Boccia, S. (Stefania), Bogdanova, N.V. (Natalia V.), Bojesen, S.E. (Stig), Bolla, M.K. (Manjeet K.), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Brenton, J.D. (James D.), Brook, R.H., Brunet, J. (Joan), Brunnström, H. (Hans), Buchanan, D.D. (Daniel D.), Burwinkel, B. (Barbara), Butzow, R. (Ralf), Cadoni, G. (Gabriella), Caldes, T. (Trinidad), Caligo, M.A. (Maria A.), Campbell, I. (Ian), Campbell, P.T. (Peter T.), Cancel-Tassin, G. (Géraldine), Cannon-Albright, L.A. (Lisa), Campa, D. (Daniele), Caporaso, N.E. (Neil), Carvalho, A.L. (André L), Chan, A.T. (Andrew T.), Chang-Claude, J. (Jenny), Chanock, S.J. (Stephen), Chen, C. (Chu), Christiani, D.C. (David C.), Claes, K.B.M. (Kathleen B M), Claessens, F. (Frank), Clements, J. (Judith), Collée, J.M. (J Margriet), Correa, M.C. (Marcia Cruz), Couch, F.J. (Fergus), Cox, A. (Angela), Cunningham, J.M. (Julie), Cybulski, C. (Cezary), Czene, K. (Kamila), Daly, M.B. (Mary), DeFazio, A. (Anna), Devilee, P. (Peter), Diez, O. (Orland), Gago-Dominguez, M. (Manuela), Donovan, J.L. (Jenny L.), Dörk, T. (Thilo), Duell, E.J. (Eric), Dunning, A.M. (Alison M.), Dwek, M. (Miriam), Eccles, D. (Diana), Edlund, C.K. (Christopher), Edwards, D.R.V. (Digna R Velez), Ellberg, C. (Carolina), Evans, D.G. (D Gareth), Fasching, P.A. (Peter), Ferris, R.L. (Robert L.), Liloglou, T. (Triantafillos), Figueiredo, J.C. (Jane C.), Fletcher, O. (Olivia), Fortner, R.T. (Renée T), Fostira, F. (Florentia), Franceschi, S. (Silvia), Friedman, E. (Eitan), Gallinger, S. (Steve), Ganz, P.A. (Patricia), Garber, J. (Judy), García-Sáenz, J.A. (José A), Gayther, S.A. (Simon), Giles, G.G. (Graham G.), Godwin, A.K. (Andrew K.), Goldberg, M.S. (Mark), Goldgar, D.E. (David E.), Goode, E.L. (Ellen), Goodman, M.T. (Marc), Goodman, G. (Gary), Grankvist, K. (Kjell), Greene, M.H. (Mark H.), Grönberg, H. (Henrik), Gronwald, J. (Jacek), Guénel, P. (Pascal), Håkansson, N. (Niclas), Hall, P. (Per), Hamann, U. (Ute), Hamdy, F. (Freddie), Hamilton, R.J. (Robert J.), Hampe, J. (Jochen), Haugen, A. (Aage), Heitz, F. (Florian), Herrero, R. (Rolando), Hillemanns, P. (Peter), Hoffmeister, M. (Michael), Høgdall, E. (Estrid), Hong, Y.-C. (Yun-Chul), Hopper, J.L. (John), Houlston, R. (Richard), Hulick, P.J. (Peter J.), Hunter, D.J. (David), Huntsman, D.G. (David G.), Idos, G. (Gregory), Imyanitov, E.N. (Evgeny), Ingles, S.A. (Sue), Isaacs, C. (Claudine), Jakubowska, A. (Anna), James, M. (Margaret), Jenkins, M.A. (Mark A.), Johansson, M. (Mattias), Johansson, M. (Mikael), John, E.M. (Esther), Joshi, A.D. (Amit D.), Kaneva, R. (Radka), Karlan, B.Y. (Beth), Kelemen, L.E. (Linda E.), Kühl, T. (Tabea), Khaw, K.-T. (Kay-Tee), Khusnutdinova, E.K. (Elza), Kibel, A. (Adam), Kiemeney, L.A. (Lambertus A.), Kim, J. (Jongoh), Kjaer, M. (Michael), Knight, J.A. (Julia), Kogevinas, M. (Manolis), Kote-Jarai, Z., Koutros, S. (Stella), Kristensen, V. (Vessela), Kupryjanczyk, J. (Jolanta), Lacko, M. (Martin), Lam, S. (Stephan), Lambrechts, D. (Diether), Landi, M.T. (Maria Teresa), Lazarus, P. (Philip), Le, N.D. (Nhu D.), Lee, E. (Eunjung), Lejbkowicz, F. (Flavio), Lenz, H.-J. (Heinz-Josef), Leslie, G. (Goska), Lessel, D. (Davor), Lester, J. (Jenny), Levine, D.A. (Douglas), Li, L. (Li), Li, C.I. (Christopher I.), Lindblom, A. (Annika), Lindor, N.M. (Noralane), Liu, G. (Geoffrey), Loupakis, F. (Fotios), Lubinski, J. (Jan), Maehle, L., Maier, C. (Christiane), Mannermaa, A. (Arto), Le Marchand, L. (Loic), Margolin, S. (Sara), May, T. (Taymaa), McGuffog, L. (Lesley), Meindl, A. (Alfons), Middha, P. (Pooja), Miller, A. (Austin), Milne, R.L. (Roger), MacInnis, R.J. (Robert J.), Modugno, F. (Francesmary), Montagna, M. (Marco), Moreno, V. (Víctor), Moysich, K.B. (Kirsten), Mucci, L. (Lorelei), Muir, K. (Kenneth), Mulligan, A.-M. (Anna-Marie), Nathanson, K.L. (Katherine), Neal, D. (David), Ness, A.R. (Andrew R.), Neuhausen, S.L. (Susan L.), Nevanlinna, H. (Heli), Newcomb, P. (Polly), Newcomb, L.F. (Lisa F.), Nielsen, F. (Finn), Nikitina-Zake, L. (Liene), Nordestgaard, B.G. (Børge), Nussbaum, R. (Robert), Offit, K. (Kenneth), Olah, E. (Edith), Olama, A.A.A. (Ali Amin Al), Olopade, O.I. (Olofunmilayo), Olshan, A.F. (Andrew F.), Olsson, H. (Håkan), Osorio, A. (Ana), Pandha, H. (Hardev), Park, J.Y. (Jong Y.), Pashayan, N. (Nora), Parsons, M. (Marilyn), Pejovic, T. (Tanja), Penney, K.L. (Kathryn L.), Peters, W.H.M. (Wilbert), Phelan, C. (Catherine), Phipps, A.I. (Amanda I.), Plaseska-Karanfilska, D. (Dijana), Pring, M. (Miranda), Prokofyeva, D. (Darya), Radice, P. (Paolo), Stefansson, K. (Kari), Ramus, S.J. (Susan), Raskin, L. (Leon), Rennert, G. (Gad), Rennert, H.S. (Hedy S.), Rensburg, E.J. (Elizabeth) van, Riggan, M.J. (Marjorie J.), Risch, H.A. (Harvey A.), Risch, A. (Angela), Roobol, M.J. (Monique J.), Rosenstein, B.S. (Barry S.), Rossing, M.A. (Mary Anne), De Ruyck, K. (Kim), Saloustros, E. (Emmanouil), Sandler, D.P. (Dale P.), Sawyer, E.J. (Elinor J.), Schabath, M.B. (Matthew), Schleutker, J. (Johanna), Schmidt, M.K. (Marjanka), Setiawan, V.W. (V Wendy), Shen, H. (Hongbing), Siegel, E.M. (Erin M.), Sieh, W. (Weiva), Singer, C.F. (Christian), Slattery, M.L. (Martha L.), Sorensen, K.D. (Karina Dalsgaard), Southey, M.C. (Melissa), Spurdle, A.B. (Amanda), Stanford, J.L. (Janet L.), Stevens, V.L. (Victoria L.), Stintzing, S. (Sebastian), Stone, J. (Jennifer), Sundfeldt, K. (Karin), Sutphen, R. (Rebecca), Swerdlow, A.J. (Anthony ), Tajara, E.H. (Eloiza H.), Tangen, C.M. (Catherine M.), Tardón, A. (Adonina), Taylor, J.A. (Jack A.), Teare, M.D. (M Dawn), Teixeira, P.J., Terry, M.B. (Mary Beth), Terry, K.L. (Kathryn L.), Thibodeau, S.N. (Stephen), Thomassen, M. (Mads), Bjørge, L. (Line), Tischkowitz, M. (Marc), Toland, A.E. (Amanda), Torres, D. (Diana), Townsend, P.A. (Paul A.), Travis, S.P.L. (Simon), Tung, N. (Nadine), Tworoger, S. (Shelley), Ulrich, C. (Cornelia), Usmani, N. (Nawaid), Vachon, C. (Celine), Van Nieuwenhuysen, E. (Els), Vega, A. (Ana), Aguado-Barrera, M.E. (Miguel Elías), Wang, Q. (Qin), Webb, P. (Penny), Weinberg, C.R. (Clarice R.), Weinstein, S. (Stephanie), Weissler, M.C. (Mark C.), Weitzel, J.N. (Jeffrey), West, C.M.L. (Catharine M L), White, E. (Emily), Whittemore, A.S. (Alice), Wichmann, H.-E. (H-Erich), Wiklund, F. (Fredrik), Winqvist, R. (Robert), Wolk, K. (Kerstin), Woll, P.J. (Penella J), Woods, M.O. (Michael), Wu, A.H. (Anna H.), Wu, X. (Xifeng), Yannoukakos, D. (Drakoulis), Zheng, W. (Wei), Zienolddiny, S. (Shanbeh), Ziogas, A. (Argyrios), Zorn, K.K. (Kristin K.), Lane, J.M. (Jacqueline M.), Saxena, R. (Richa), Thomas, D.C. (Duncan), Hung, R.J. (Rayjean J.), Diergaarde, B. (Brenda), McKay, J. (James), Peters, U. (Ulrike), Hsu, L. (Li), García-Closas, M. (Montserrat), Eeles, R.A. (Rosalind A.), Chenevix-Trench, G. (Georgia), Brennan, P.J. (Paul J.), Haiman, C.A. (Christopher), Simard, J. (Jacques), Easton, D.F. (Douglas), Gruber, S.B. (Stephen), Pharoah, P.D.P. (Paul), Price, A.L. (Alkes L.), Pasaniuc, B. (Bogdan), Amos, C.I. (Christopher I.), Kraft, P. (Peter), Lindström, S. (Sara), Jiang, X. (Xia), Finucane, H.K. (Hilary K.), Schumacher, F.R. (Fredrick R), Schmit, S.L. (Stephanie L.), Tyrer, J.P. (Jonathan P.), Han, Y. (Younghun), Michailidou, K. (Kyriaki), Lesseur, C. (Corina), Kuchenbaecker, K.B. (Karoline), Dennis, J. (Joe), Conti, G. (Giario), Casey, G. (Graham), Gaudet, M.M. (Mia M.), Huyghe, J.R. (Jeroen R.), Albanes, D. (Demetrius), Aldrich, M.C. (Melinda), Andrew, A.S. (Angeline S.), Andrulis, I.L. (Irene L.), Anton-Culver, H. (Hoda), Antoniou, A.C. (Antonis C.), Antonenkova, N.N. (Natalia N.), Arnold, S.M. (Susanne M.), Aronson, K.J. (Kristan J.), Arun, B.K. (Banu), Bandera, E.V. (Elisa), Barkardottir, R.B. (Rosa B.), Barnes, D. (Daniel), Batra, J. (Jyotsna), Beckmann, M.W. (Matthias), Benítez, J. (Javier), Benlloch, S. (Sara), Berchuck, A. (Andrew), Berndt, S.I. (Sonja), Bickeböller, H. (Heike), Bien, S.A. (Stephanie A.), Blomqvist, C. (Carl), Boccia, S. (Stefania), Bogdanova, N.V. (Natalia V.), Bojesen, S.E. (Stig), Bolla, M.K. (Manjeet K.), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Brenton, J.D. (James D.), Brook, R.H., Brunet, J. (Joan), Brunnström, H. (Hans), Buchanan, D.D. (Daniel D.), Burwinkel, B. (Barbara), Butzow, R. (Ralf), Cadoni, G. (Gabriella), Caldes, T. (Trinidad), Caligo, M.A. (Maria A.), Campbell, I. (Ian), Campbell, P.T. (Peter T.), Cancel-Tassin, G. (Géraldine), Cannon-Albright, L.A. (Lisa), Campa, D. (Daniele), Caporaso, N.E. (Neil), Carvalho, A.L. (André L), Chan, A.T. (Andrew T.), Chang-Claude, J. (Jenny), Chanock, S.J. (Stephen), Chen, C. (Chu), Christiani, D.C. (David C.), Claes, K.B.M. (Kathleen B M), Claessens, F. (Frank), Clements, J. (Judith), Collée, J.M. (J Margriet), Correa, M.C. (Marcia Cruz), Couch, F.J. (Fergus), Cox, A. (Angela), Cunningham, J.M. (Julie), Cybulski, C. (Cezary), Czene, K. (Kamila), Daly, M.B. (Mary), DeFazio, A. (Anna), Devilee, P. (Peter), Diez, O. (Orland), Gago-Dominguez, M. (Manuela), Donovan, J.L. (Jenny L.), Dörk, T. (Thilo), Duell, E.J. (Eric), Dunning, A.M. (Alison M.), Dwek, M. (Miriam), Eccles, D. (Diana), Edlund, C.K. (Christopher), Edwards, D.R.V. (Digna R Velez), Ellberg, C. (Carolina), Evans, D.G. (D Gareth), Fasching, P.A. (Peter), Ferris, R.L. (Robert L.), Liloglou, T. (Triantafillos), Figueiredo, J.C. (Jane C.), Fletcher, O. (Olivia), Fortner, R.T. (Renée T), Fostira, F. (Florentia), Franceschi, S. (Silvia), Friedman, E. (Eitan), Gallinger, S. (Steve), Ganz, P.A. (Patricia), Garber, J. (Judy), García-Sáenz, J.A. (José A), Gayther, S.A. (Simon), Giles, G.G. (Graham G.), Godwin, A.K. (Andrew K.), Goldberg, M.S. (Mark), Goldgar, D.E. (David E.), Goode, E.L. (Ellen), Goodman, M.T. (Marc), Goodman, G. (Gary), Grankvist, K. (Kjell), Greene, M.H. (Mark H.), Grönberg, H. (Henrik), Gronwald, J. (Jacek), Guénel, P. (Pascal), Håkansson, N. (Niclas), Hall, P. (Per), Hamann, U. (Ute), Hamdy, F. (Freddie), Hamilton, R.J. (Robert J.), Hampe, J. (Jochen), Haugen, A. (Aage), Heitz, F. (Florian), Herrero, R. (Rolando), Hillemanns, P. (Peter), Hoffmeister, M. (Michael), Høgdall, E. (Estrid), Hong, Y.-C. (Yun-Chul), Hopper, J.L. (John), Houlston, R. (Richard), Hulick, P.J. (Peter J.), Hunter, D.J. (David), Huntsman, D.G. (David G.), Idos, G. (Gregory), Imyanitov, E.N. (Evgeny), Ingles, S.A. (Sue), Isaacs, C. (Claudine), Jakubowska, A. (Anna), James, M. (Margaret), Jenkins, M.A. (Mark A.), Johansson, M. (Mattias), Johansson, M. (Mikael), John, E.M. (Esther), Joshi, A.D. (Amit D.), Kaneva, R. (Radka), Karlan, B.Y. (Beth), Kelemen, L.E. (Linda E.), Kühl, T. (Tabea), Khaw, K.-T. (Kay-Tee), Khusnutdinova, E.K. (Elza), Kibel, A. (Adam), Kiemeney, L.A. (Lambertus A.), Kim, J. (Jongoh), Kjaer, M. (Michael), Knight, J.A. (Julia), Kogevinas, M. (Manolis), Kote-Jarai, Z., Koutros, S. (Stella), Kristensen, V. (Vessela), Kupryjanczyk, J. (Jolanta), Lacko, M. (Martin), Lam, S. (Stephan), Lambrechts, D. (Diether), Landi, M.T. (Maria Teresa), Lazarus, P. (Philip), Le, N.D. (Nhu D.), Lee, E. (Eunjung), Lejbkowicz, F. (Flavio), Lenz, H.-J. (Heinz-Josef), Leslie, G. (Goska), Lessel, D. (Davor), Lester, J. (Jenny), Levine, D.A. (Douglas), Li, L. (Li), Li, C.I. (Christopher I.), Lindblom, A. (Annika), Lindor, N.M. (Noralane), Liu, G. (Geoffrey), Loupakis, F. (Fotios), Lubinski, J. (Jan), Maehle, L., Maier, C. (Christiane), Mannermaa, A. (Arto), Le Marchand, L. (Loic), Margolin, S. (Sara), May, T. (Taymaa), McGuffog, L. (Lesley), Meindl, A. (Alfons), Middha, P. (Pooja), Miller, A. (Austin), Milne, R.L. (Roger), MacInnis, R.J. (Robert J.), Modugno, F. (Francesmary), Montagna, M. (Marco), Moreno, V. (Víctor), Moysich, K.B. (Kirsten), Mucci, L. (Lorelei), Muir, K. (Kenneth), Mulligan, A.-M. (Anna-Marie), Nathanson, K.L. (Katherine), Neal, D. (David), Ness, A.R. (Andrew R.), Neuhausen, S.L. (Susan L.), Nevanlinna, H. (Heli), Newcomb, P. (Polly), Newcomb, L.F. (Lisa F.), Nielsen, F. (Finn), Nikitina-Zake, L. (Liene), Nordestgaard, B.G. (Børge), Nussbaum, R. (Robert), Offit, K. (Kenneth), Olah, E. (Edith), Olama, A.A.A. (Ali Amin Al), Olopade, O.I. (Olofunmilayo), Olshan, A.F. (Andrew F.), Olsson, H. (Håkan), Osorio, A. (Ana), Pandha, H. (Hardev), Park, J.Y. (Jong Y.), Pashayan, N. (Nora), Parsons, M. (Marilyn), Pejovic, T. (Tanja), Penney, K.L. (Kathryn L.), Peters, W.H.M. (Wilbert), Phelan, C. (Catherine), Phipps, A.I. (Amanda I.), Plaseska-Karanfilska, D. (Dijana), Pring, M. (Miranda), Prokofyeva, D. (Darya), Radice, P. (Paolo), Stefansson, K. (Kari), Ramus, S.J. (Susan), Raskin, L. (Leon), Rennert, G. (Gad), Rennert, H.S. (Hedy S.), Rensburg, E.J. (Elizabeth) van, Riggan, M.J. (Marjorie J.), Risch, H.A. (Harvey A.), Risch, A. (Angela), Roobol, M.J. (Monique J.), Rosenstein, B.S. (Barry S.), Rossing, M.A. (Mary Anne), De Ruyck, K. (Kim), Saloustros, E. (Emmanouil), Sandler, D.P. (Dale P.), Sawyer, E.J. (Elinor J.), Schabath, M.B. (Matthew), Schleutker, J. (Johanna), Schmidt, M.K. (Marjanka), Setiawan, V.W. (V Wendy), Shen, H. (Hongbing), Siegel, E.M. (Erin M.), Sieh, W. (Weiva), Singer, C.F. (Christian), Slattery, M.L. (Martha L.), Sorensen, K.D. (Karina Dalsgaard), Southey, M.C. (Melissa), Spurdle, A.B. (Amanda), Stanford, J.L. (Janet L.), Stevens, V.L. (Victoria L.), Stintzing, S. (Sebastian), Stone, J. (Jennifer), Sundfeldt, K. (Karin), Sutphen, R. (Rebecca), Swerdlow, A.J. (Anthony ), Tajara, E.H. (Eloiza H.), Tangen, C.M. (Catherine M.), Tardón, A. (Adonina), Taylor, J.A. (Jack A.), Teare, M.D. (M Dawn), Teixeira, P.J., Terry, M.B. (Mary Beth), Terry, K.L. (Kathryn L.), Thibodeau, S.N. (Stephen), Thomassen, M. (Mads), Bjørge, L. (Line), Tischkowitz, M. (Marc), Toland, A.E. (Amanda), Torres, D. (Diana), Townsend, P.A. (Paul A.), Travis, S.P.L. (Simon), Tung, N. (Nadine), Tworoger, S. (Shelley), Ulrich, C. (Cornelia), Usmani, N. (Nawaid), Vachon, C. (Celine), Van Nieuwenhuysen, E. (Els), Vega, A. (Ana), Aguado-Barrera, M.E. (Miguel Elías), Wang, Q. (Qin), Webb, P. (Penny), Weinberg, C.R. (Clarice R.), Weinstein, S. (Stephanie), Weissler, M.C. (Mark C.), Weitzel, J.N. (Jeffrey), West, C.M.L. (Catharine M L), White, E. (Emily), Whittemore, A.S. (Alice), Wichmann, H.-E. (H-Erich), Wiklund, F. (Fredrik), Winqvist, R. (Robert), Wolk, K. (Kerstin), Woll, P.J. (Penella J), Woods, M.O. (Michael), Wu, A.H. (Anna H.), Wu, X. (Xifeng), Yannoukakos, D. (Drakoulis), Zheng, W. (Wei), Zienolddiny, S. (Shanbeh), Ziogas, A. (Argyrios), Zorn, K.K. (Kristin K.), Lane, J.M. (Jacqueline M.), Saxena, R. (Richa), Thomas, D.C. (Duncan), Hung, R.J. (Rayjean J.), Diergaarde, B. (Brenda), McKay, J. (James), Peters, U. (Ulrike), Hsu, L. (Li), García-Closas, M. (Montserrat), Eeles, R.A. (Rosalind A.), Chenevix-Trench, G. (Georgia), Brennan, P.J. (Paul J.), Haiman, C.A. (Christopher), Simard, J. (Jacques), Easton, D.F. (Douglas), Gruber, S.B. (Stephen), Pharoah, P.D.P. (Paul), Price, A.L. (Alkes L.), Pasaniuc, B. (Bogdan), Amos, C.I. (Christopher I.), Kraft, P. (Peter), and Lindström, S. (Sara)
Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Published: 2019
Full Text: View/download PDF

31. Hereditary breast/ovarian and colorectal cancer genetics knowledge in a national sample of US physicians

Author: Wideroff, L., Vadaparampil, S.T., Greene, M.H., Taplin, S., Olson, L., and Freedman, A.N.
Subjects: Breast cancer -- Genetic aspects, Colorectal cancer -- Genetic aspects, Ovarian cancer -- Genetic aspects, Cancer -- Diagnosis, Cancer -- Genetic aspects, Cancer -- Care and treatment, Cancer -- Research, Health
Published: 2005

32. A twofold increase in BRCA mutation related prostate cancer among Ashkenazi Israelis is not associated with distinctive histopathology

Author: Giusti, R M., Rutter, J L., Duray, P H., Freedman, L S., Konichezky, M., Fisher - Fischbein, J., Greene, M.H., Maslansky, B., Fischbein, A., Gruber, S.B., Rennert, G., Ronchetti, R.D., Hewitt, S.M., Struewing, J.P., and Iscovich, J.
Subjects: Gene mutations -- Physiological aspects -- Health aspects -- Research -- Analysis -- Genetic aspects, Genetic research -- Analysis -- Physiological aspects -- Genetic aspects -- Health aspects, Prostate cancer -- Health aspects -- Genetic aspects -- Care and treatment -- Demographic aspects -- Research, Cancer patients -- Demographic aspects -- Genetic aspects -- Health aspects -- Care and treatment, Ashkenazim -- Genetic aspects -- Health aspects -- Physiological aspects -- Research -- Analysis, Medical genetics -- Research -- Health aspects -- Analysis -- Physiological aspects, Health, Care and treatment, Physiological aspects, Analysis, Research, Genetic aspects, Demographic aspects, Health aspects
Abstract: J Med Genet 2003;40:787-792 The magnitude of the risk of prostate cancer among Ashkenazi Jewish carriers of the common mutations in the BRCA1 and BRCA2 genes, the so-called Ashkenazi BRCA [...]
Published: 2003

33. Family history of breast cancer as a determinant of the risk of developing endometrial cancer: a nationwide cohort study. (Letter to JMG)

Author: Kazerouni, N., Schairer, C., Friedman, H.B., Lacey, Jr., J.V., and Greene, M.H.
Subjects: Familial diseases -- Genetic aspects -- Research -- Risk factors, Endometrial cancer -- Risk factors -- Genetic aspects -- Research, Medical genetics -- Research, Breast cancer -- Research -- Risk factors -- Genetic aspects, Health
Abstract: Despite recent declines in its incidence, endometrial cancer remains the most common cancer of the female reproductive tract in the United States (1) and in the western world. (2) Well [...]
Published: 2002

34. Desmoid tumors in familial adenomatous polyposis: a pilot project evaluating efficacy of treatment with pirfenidone

Author: Lindor, N.M, Dozois, R, Nelson, H, Wolff, B, King, J, Boardman, L, Wilson, M, Greene, M.H, Karnes, W, Jr., Mesa, R, Welch, T, Edmonson, J, and Limburg, P
Published: 2003
Full Text: View/download PDF

35. Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations

Author: Rebbeck, T.R., Friebel, T.M., Friedman, E., Hamann, U., Huo, D., Kwong, A., Olah, E., Olopade, O.I., Solano, A.R., Teo, S.H., Thomassen, M., Weitzel, J.N., Chan, T.L., Couch, F.J., Goldgar, D.E., Kruse, T.A., Palmero, E.I., Park, S.K., Torres, D., Rensburg, E.J. van, McGuffog, L., Parsons, M.T., Leslie, G., Aalfs, C.M., Abugattas, J., Adlard, J., Agata, S., Aittomaki, K., Andrews, L., Andrulis, I.L., Arason, A., Arnold, N., Arun, B.K., Asseryanis, E., Auerbach, L., Azzollini, J., Balmana, J., Barile, M., Barkardottir, R.B., Barrowdale, D., Benitez, J., Berger, A., Berger, R., Blanco, A.M., Blazer, K.R., Blok, M.J., Bonadona, V., Bonanni, B., Bradbury, A.R., Brewer, C., Buecher, B., Buys, S.S., Caldes, T., Caliebe, A., Caligo, M.A., Campbell, I., Caputo, S.M., Chiquette, J., Chung, W.K., Claes, K.B.M., Collee, J.M., Cook, J., Davidson, R., Hoya, M. de la, Leeneer, K. De, Pauw, A. de, Delnatte, C., Diez, O., Ding, Y.C., Ditsch, N., Domchek, S.M., Dorfling, C.M., Velazquez, C., Dworniczak, B., Eason, J., Easton, D.F., Eeles, R., Ehrencrona, H., Ejlertsen, B., Engel, C., Engert, S., Evans, D.G., Faivre, L., Feliubadalo, L., Ferrer, S.F., Foretova, L., Fowler, J., Frost, D., Galvao, H.C.R., Ganz, P.A., Garber, J., Gauthier-Villars, M., Gehrig, A., Gerdes, A.M., Gesta, P., Giannini, G., Giraud, S., Glendon, G., Godwin, A.K., Greene, M.H., Mensenkamp, A.R., Antoniou, A.C., Nathanson, K.L., Rebbeck, T.R., Friebel, T.M., Friedman, E., Hamann, U., Huo, D., Kwong, A., Olah, E., Olopade, O.I., Solano, A.R., Teo, S.H., Thomassen, M., Weitzel, J.N., Chan, T.L., Couch, F.J., Goldgar, D.E., Kruse, T.A., Palmero, E.I., Park, S.K., Torres, D., Rensburg, E.J. van, McGuffog, L., Parsons, M.T., Leslie, G., Aalfs, C.M., Abugattas, J., Adlard, J., Agata, S., Aittomaki, K., Andrews, L., Andrulis, I.L., Arason, A., Arnold, N., Arun, B.K., Asseryanis, E., Auerbach, L., Azzollini, J., Balmana, J., Barile, M., Barkardottir, R.B., Barrowdale, D., Benitez, J., Berger, A., Berger, R., Blanco, A.M., Blazer, K.R., Blok, M.J., Bonadona, V., Bonanni, B., Bradbury, A.R., Brewer, C., Buecher, B., Buys, S.S., Caldes, T., Caliebe, A., Caligo, M.A., Campbell, I., Caputo, S.M., Chiquette, J., Chung, W.K., Claes, K.B.M., Collee, J.M., Cook, J., Davidson, R., Hoya, M. de la, Leeneer, K. De, Pauw, A. de, Delnatte, C., Diez, O., Ding, Y.C., Ditsch, N., Domchek, S.M., Dorfling, C.M., Velazquez, C., Dworniczak, B., Eason, J., Easton, D.F., Eeles, R., Ehrencrona, H., Ejlertsen, B., Engel, C., Engert, S., Evans, D.G., Faivre, L., Feliubadalo, L., Ferrer, S.F., Foretova, L., Fowler, J., Frost, D., Galvao, H.C.R., Ganz, P.A., Garber, J., Gauthier-Villars, M., Gehrig, A., Gerdes, A.M., Gesta, P., Giannini, G., Giraud, S., Glendon, G., Godwin, A.K., Greene, M.H., Mensenkamp, A.R., Antoniou, A.C., and Nathanson, K.L.
Abstract: Item does not contain fulltext, The prevalence and spectrum of germline mutations in BRCA1 and BRCA2 have been reported in single populations, with the majority of reports focused on White in Europe and North America. The Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) has assembled data on 18,435 families with BRCA1 mutations and 11,351 families with BRCA2 mutations ascertained from 69 centers in 49 countries on six continents. This study comprehensively describes the characteristics of the 1,650 unique BRCA1 and 1,731 unique BRCA2 deleterious (disease-associated) mutations identified in the CIMBA database. We observed substantial variation in mutation type and frequency by geographical region and race/ethnicity. In addition to known founder mutations, mutations of relatively high frequency were identified in specific racial/ethnic or geographic groups that may reflect founder mutations and which could be used in targeted (panel) first pass genotyping for specific populations. Knowledge of the population-specific mutational spectrum in BRCA1 and BRCA2 could inform efficient strategies for genetic testing and may justify a more broad-based oncogenetic testing in some populations.
Published: 2018

36. Prediction of Breast and Prostate Cancer Risks in Male BRCA1 and BRCA2 Mutation Carriers Using Polygenic Risk Scores

Author: Lecarpentier, J., Silvestri, V., Kuchenbaecker, K.B., Barrowdale, D., Dennis, J., McGuffog, L., Soucy, P., Leslie, G., Rizzolo, P., Navazio, A.S., Valentini, V., Zelli, V., Lee, A., Olama, A.A. al, Tyrer, J.P., Southey, M., John, E.M., Conner, T.A., Goldgar, D.E., Buys, S.S., Janavicius, R., Steele, L., Ding, Y.C., Neuhausen, S.L., Hansen, T.V.O., Osorio, A., Weitzel, J.N., Toss, A., Medici, V., Cortesi, L., Zanna, I., Palli, D., Radice, P., Manoukian, S., Peissel, B., Azzollini, J., Viel, A., Cini, G., Damante, G., Tommasi, S., Peterlongo, P., Fostira, F., Hamann, U., Evans, D.G., Henderson, A., Brewer, C., Eccles, D., Cook, J., Ong, K.R., Walker, L., Side, L.E., Porteous, M.E., Davidson, R., Hodgson, S., Frost, D., Adlard, J., Izatt, L., Eeles, R., Ellis, S., Tischkowitz, M., Godwin, A.K., Meindl, A., Gehrig, A., Dworniczak, B., Sutter, C., Engel, C., Niederacher, D., Steinemann, D., Hahnen, E., Hauke, J., Rhiem, K., Kast, K., Arnold, N., Ditsch, N., Wang-Gohrke, S., Wappenschmidt, B., Wand, D., Lasset, C., Stoppa-Lyonnet, D., Belotti, M., Damiola, F., Barjhoux, L., Mazoyer, S., Heetvelde, M. van, Poppe, B., Leeneer, K. de, Claes, K.B.M., Hoya, M. de la, Garcia-Barberan, V., Caldes, T., Perez Segura, P., Kiiski, J.I., Aittomaki, K., Khan, S., Nevanlinna, H., Asperen, C.J. van, Vaszko, T., Kasler, M., Olah, E., Balmana, J., Gutierrez-Enriquez, S., Diez, O., Teule, A., Izquierdo, A., Darder, E., Brunet, J., Valle, J. del, Feliubadalo, L., Pujana, M.A., Lazaro, C., Arason, A., Agnarsson, B.A., Johannsson, O.T., Barkardottir, R.B., Alducci, E., Tognazzo, S., Montagna, M., Teixeira, M.R., Pinto, P., Spurdle, A.B., Holland, H., Lee, J.W., Lee, M.H., Lee, J., Kim, S.W., Kang, E., Kim, Z., Sharma, P., Rebbeck, T.R., Vijai, J., Robson, M., Lincoln, A., Musinsky, J., Gaddam, P., Tan, Y.Y., Berger, A., Singer, C.F., Loud, J.T., Greene, M.H., Mulligan, A.M., Glendon, G., Andrulis, I.L., Toland, A.E., Senter, L., Bojesen, A., Nielsen, H.R., Skytte, A.B., Sunde, L., Jensen, U.B., Pedersen, I.S., Krogh, L., Kruse, T.A., Caligo, M.A., Yoon, S.Y., Teo, S.H., Wachenfeldt, A. von, Huo, D., Nielsen, S.M., Olopade, O.I., Nathanson, K.L., Domchek, S.M., Lorenchick, C., Jankowitz, R.C., Campbell, I., James, P., Mitchell, G., Orr, N., Park, S.K., Thomassen, M., Offit, K., Couch, F.J., Simard, J., Easton, D.F., Chenevix-Trench, G., Schmutzler, R.K., Antoniou, A.C., Ottini, L., EMBRACE, GEMO Study Collaborators, HEBON, KConFab Investigators, Dennis, Joe [0000-0003-4591-1214], Leslie, Goska [0000-0001-5756-6222], Lee, Andrew [0000-0003-0677-0252], Amin Al Olama, Ali [0000-0002-7178-3431], Tyrer, Jonathan [0000-0003-3724-4757], Tischkowitz, Marc [0000-0002-7880-0628], Easton, Douglas [0000-0003-2444-3247], Antoniou, Antonis [0000-0001-9223-3116], and Apollo - University of Cambridge Repository
Subjects: Adult, Aged, 80 and over, Male, Heterozygote, Multifactorial Inheritance, Genes, BRCA2, Age Factors, Genes, BRCA1, Prostatic Neoplasms, Middle Aged, Polymorphism, Single Nucleotide, Risk Assessment, Breast Neoplasms, Male, Case-Control Studies, Mutation, Humans, Genetic Predisposition to Disease, Genetic Testing, skin and connective tissue diseases, Aged, Genome-Wide Association Study
Abstract: $\textbf{Purpose}$ $\textit{BRCA1/2}$ mutations increase the risk of breast and prostate cancer in men. Common genetic variants modify cancer risks for female carriers of $\textit{BRCA1/2}$ mutations. We investigated-for the first time to our knowledge-associations of common genetic variants with breast and prostate cancer risks for male carriers of $\textit{BRCA1/2}$ mutations and implications for cancer risk prediction. $\textbf{Materials and Methods}$ We genotyped 1,802 male carriers of $\textit{BRCA1/2}$ mutations from the Consortium of Investigators of Modifiers of $\textit{BRCA1/2}$ by using the custom Illumina OncoArray. We investigated the combined effects of established breast and prostate cancer susceptibility variants on cancer risks for male carriers of $\textit{BRCA1/2}$ mutations by constructing weighted polygenic risk scores (PRSs) using published effect estimates as weights. $\textbf{Results}$ In male carriers of $\textit{BRCA1/2}$ mutations, PRS that was based on 88 female breast cancer susceptibility variants was associated with breast cancer risk (odds ratio per standard deviation of PRS, 1.36; 95% CI, 1.19 to 1.56; $P$ = 8.6 × 10$^{-6}$)). Similarly, PRS that was based on 103 prostate cancer susceptibility variants was associated with prostate cancer risk (odds ratio per SD of PRS, 1.56; 95% CI, 1.35 to 1.81; $P$ = 3.2 × 10$^{-9}$)). Large differences in absolute cancer risks were observed at the extremes of the PRS distribution. For example, prostate cancer risk by age 80 years at the 5th and 95th percentiles of the PRS varies from 7% to 26% for carriers of $\textit{BRCA1}$ mutations and from 19% to 61% for carriers of $\textit{BRCA2}$ mutations, respectively. $\textbf{Conclusion}$ PRSs may provide informative cancer risk stratification for male carriers of $\textit{BRCA1/2}$ mutations that might enable these men and their physicians to make informed decisions on the type and timing of breast and prostate cancer risk management.
Published: 2017

37. Meta-analysis of five genome-wide association studies identifies multiple new loci associated with testicular germ cell tumor

Author: Wang, Z., McGlynn, K.A., Rajpert- de Meyts, E., Bishop, D.T., Chung, C.C., Dalgaard, M.D., Greene, M.H., Gupta, R, Grotmol, T., Haugen, T.B., Karlsson, R., Litchfield, K., Mitra, N., Nielsen, K., Pyle, L.C., Schwartz, S.M., Thorsson, V., Vardhanabhuti, S., Wiklund, F., Turnbull, C., Chanock, S.J., Kanetsky, P.A., Nathanson, K.L., Kiemeney, B., Skotheim, R.I., Zheng, T., Wang, Z., McGlynn, K.A., Rajpert- de Meyts, E., Bishop, D.T., Chung, C.C., Dalgaard, M.D., Greene, M.H., Gupta, R, Grotmol, T., Haugen, T.B., Karlsson, R., Litchfield, K., Mitra, N., Nielsen, K., Pyle, L.C., Schwartz, S.M., Thorsson, V., Vardhanabhuti, S., Wiklund, F., Turnbull, C., Chanock, S.J., Kanetsky, P.A., Nathanson, K.L., Kiemeney, B., Skotheim, R.I., and Zheng, T.
Abstract: Item does not contain fulltext, The international Testicular Cancer Consortium (TECAC) combined five published genome-wide association studies of testicular germ cell tumor (TGCT; 3,558 cases and 13,970 controls) to identify new susceptibility loci. We conducted a fixed-effects meta-analysis, including, to our knowledge, the first analysis of the X chromosome. Eight new loci mapping to 2q14.2, 3q26.2, 4q35.2, 7q36.3, 10q26.13, 15q21.3, 15q22.31, and Xq28 achieved genome-wide significance (P < 5 x 10-8). Most loci harbor biologically plausible candidate genes. We refined previously reported associations at 9p24.3 and 19p12 by identifying one and three additional independent SNPs, respectively. In aggregate, the 39 independent markers identified to date explain 37% of father-to-son familial risk, 8% of which can be attributed to the 12 new signals reported here. Our findings substantially increase the number of known TGCT susceptibility alleles, move the field closer to a comprehensive understanding of the underlying genetic architecture of TGCT, and provide further clues to the etiology of TGCT.
Published: 2017

38. Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression: identification of a modifier of breast cancer risk at locus 11q22.3

Author: Hamdi, Y., Soucy, P., Kuchenbaeker, K.B., Pastinen, T., Droit, A., Lemacon, A., Adlard, J., Aittomaki, K., Andrulis, I.L., Arason, A., Arnold, N., Arun, B.K., Azzollini, J., Bane, A., Barjhoux, L., Barrowdale, D., Benitez, J., Berthet, P., Blok, M.J., Bobolis, K., Bonadona, V., Bonanni, B., Bradbury, A.R., Brewer, C., Buecher, B., Buys, S.S., Caligo, M.A., Chiquette, J., Chung, W.K., Claes, K.B., Daly, M.B., Damiola, F., Davidson, R., Hoya, M. de la, Leeneer, K. De, Diez, O., Ding, Y.C., Dolcetti, R., Domchek, S.M., Dorfling, C.M., Eccles, D., Eeles, R., Einbeigi, Z., Ejlertsen, B., Engel, C., Evans, D., Feliubadalo, L., Foretova, L., Fostira, F., Foulkes, W.D., Fountzilas, G., Friedman, E., Frost, D., Ganschow, P., Ganz, P.A., Garber, J., Gayther, S.A., Gerdes, A.M., Glendon, G., Godwin, A.K., Goldgar, D.E., Greene, M.H., Gronwald, J., Hahnen, E., Hamann, U., Hansen, T.V., Hart, S., Hays, J.L., Hogervorst, F.B., Hulick, P.J., Imyanitov, E.N., Isaacs, C., Izatt, L., Jakubowska, A., James, P., Janavicius, R., Jensen, U.B., John, E.M., Joseph, V., Just, W., Kaczmarek, K., Karlan, B.Y., Kets, C.M., Kirk, J., Kriege, M., Laitman, Y., Laurent, M., Lazaro, C., Leslie, G., Lester, J., Lesueur, F., Liljegren, A., Loman, N., Loud, J.T., Manoukian, S., Mariani, M., Mazoyer, S., McGuffog, L., Meijers-Heijboer, H.E., Meindl, A., et al., Hamdi, Y., Soucy, P., Kuchenbaeker, K.B., Pastinen, T., Droit, A., Lemacon, A., Adlard, J., Aittomaki, K., Andrulis, I.L., Arason, A., Arnold, N., Arun, B.K., Azzollini, J., Bane, A., Barjhoux, L., Barrowdale, D., Benitez, J., Berthet, P., Blok, M.J., Bobolis, K., Bonadona, V., Bonanni, B., Bradbury, A.R., Brewer, C., Buecher, B., Buys, S.S., Caligo, M.A., Chiquette, J., Chung, W.K., Claes, K.B., Daly, M.B., Damiola, F., Davidson, R., Hoya, M. de la, Leeneer, K. De, Diez, O., Ding, Y.C., Dolcetti, R., Domchek, S.M., Dorfling, C.M., Eccles, D., Eeles, R., Einbeigi, Z., Ejlertsen, B., Engel, C., Evans, D., Feliubadalo, L., Foretova, L., Fostira, F., Foulkes, W.D., Fountzilas, G., Friedman, E., Frost, D., Ganschow, P., Ganz, P.A., Garber, J., Gayther, S.A., Gerdes, A.M., Glendon, G., Godwin, A.K., Goldgar, D.E., Greene, M.H., Gronwald, J., Hahnen, E., Hamann, U., Hansen, T.V., Hart, S., Hays, J.L., Hogervorst, F.B., Hulick, P.J., Imyanitov, E.N., Isaacs, C., Izatt, L., Jakubowska, A., James, P., Janavicius, R., Jensen, U.B., John, E.M., Joseph, V., Just, W., Kaczmarek, K., Karlan, B.Y., Kets, C.M., Kirk, J., Kriege, M., Laitman, Y., Laurent, M., Lazaro, C., Leslie, G., Lester, J., Lesueur, F., Liljegren, A., Loman, N., Loud, J.T., Manoukian, S., Mariani, M., Mazoyer, S., McGuffog, L., Meijers-Heijboer, H.E., Meindl, A., and et al.
Abstract: Contains fulltext : 169901.pdf (publisher's version ) (Open Access), PURPOSE: Cis-acting regulatory SNPs resulting in differential allelic expression (DAE) may, in part, explain the underlying phenotypic variation associated with many complex diseases. To investigate whether common variants associated with DAE were involved in breast cancer susceptibility among BRCA1 and BRCA2 mutation carriers, a list of 175 genes was developed based of their involvement in cancer-related pathways. METHODS: Using data from a genome-wide map of SNPs associated with allelic expression, we assessed the association of ~320 SNPs located in the vicinity of these genes with breast and ovarian cancer risks in 15,252 BRCA1 and 8211 BRCA2 mutation carriers ascertained from 54 studies participating in the Consortium of Investigators of Modifiers of BRCA1/2. RESULTS: We identified a region on 11q22.3 that is significantly associated with breast cancer risk in BRCA1 mutation carriers (most significant SNP rs228595 p = 7 x 10-6). This association was absent in BRCA2 carriers (p = 0.57). The 11q22.3 region notably encompasses genes such as ACAT1, NPAT, and ATM. Expression quantitative trait loci associations were observed in both normal breast and tumors across this region, namely for ACAT1, ATM, and other genes. In silico analysis revealed some overlap between top risk-associated SNPs and relevant biological features in mammary cell data, which suggests potential functional significance. CONCLUSION: We identified 11q22.3 as a new modifier locus in BRCA1 carriers. Replication in larger studies using estrogen receptor (ER)-negative or triple-negative (i.e., ER-, progesterone receptor-, and HER2-negative) cases could therefore be helpful to confirm the association of this locus with breast cancer risk.
Published: 2017

39. Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer

Author: Phelan, C. (Catherine), Kuchenbaecker, K.B. (Karoline), Tyrer, J.P. (Jonathan P.), Kar, S.P. (Siddhartha P.), Lawrenson, K. (Kate), Winham, S.J. (Stacey J.), Dennis, J. (Joe), Pirie, A. (Ailith), Riggan, M.J. (Marjorie J.), Chornokur, G. (Ganna), Earp, M.A. (Madalene A.), Lyra, P.C. (Paulo C.), Lee, J.M. (Janet M.), Coetzee, S. (Simon), Beesley, J. (Jonathan), McGuffog, L. (Lesley), Soucy, P. (Penny), Dicks, E. (Ed), Lee, A. (Andrew), Barrowdale, D. (Daniel), Lecarpentier, J. (Julie), Leslie, G. (Goska), Aalfs, C.M. (Cora), Aben, K.K.H. (Katja), Adams, M. (Marcia), Adlard, J.W. (Julian), Andrulis, I.L. (Irene), Anton-Culver, H. (Hoda), Antonenkova, N. (Natalia), Aravantinos, G. (Gerasimos), Arnold, N. (Norbert), Arun, B.K. (Banu), Arver, B. (Brita), Azzollini, J., Balmana, J. (Judith), Banerjee, S. (Susana), Barjhoux, L. (Laure), Barkardottir, R.B. (Rosa B.), Bean, Y. (Yukie), Beckmann, M.W. (Matthias), Beeghly-Fadiel, A. (Alicia), Benítez, J. (Javier), Bermisheva, M. (Marina), Bernardini, M.Q. (Marcus Q.), Birrer, M.J. (Michael J.), Bjorge, L. (Line), Black, A., Blankstein, K. (Kenneth), Blok, M.J. (Marinus), Bodelon, C. (Clara), Bogdanova, N. (Natalia), Bojesen, A. (Anders), Bonanni, B. (Bernardo), Borg, Å. (Åke), Bradbury, A.R. (Angela R.), Brenton, J.D. (James D.), Brewer, C. (Carole), Brinton, L.A. (Louise), Broberg, P. (Per), Brooks-Wilson, A. (Angela), Bruinsma, F. (Fiona), Brunet, J. (Joan), Buecher, B. (Bruno), Butzow, R. (Ralf), Buys, S.S. (Saundra), Caldes, T. (Trinidad), Caligo, M.A. (Maria A.), Campbell, I. (Ian), Cannioto, R. (Rikki), Carney, M.E. (Michael), Cescon, T. (Terence), Chan, S. (Salina), Chang-Claude, J. (Jenny), Chanock, S.J. (Stephen), Chen, X.Q. (Xiao Qing), Chiew, Y.-E. (Yoke-Eng), Chiquette, J. (Jocelyne), Chung, W. (Wendy), Claes, K. (Kathleen), Conner, T. (Thomas), Cook, L.S. (Linda S.), Cook, J. (Jackie), Cramer, D.W. (Daniel), Cunningham, J.M. (Julie), D'Aloisio, A.A. (Aimee A.), Daly, M.B. (Mary), Damiola, F. (Francesca), Damirovna, S.D. (Sakaeva Dina), Dansonka-Mieszkowska, A. (Agnieszka), Dao, F. (Fanny), Davidson, R. (Rosemarie), DeFazio, A. (Anna), Delnatte, C.D. (Capucine), Doheny, K.F. (Kimberly), Díez, O. (Orland), Ding, Y.C. (Yuan Chun), Doherty, J.A. (Jennifer), Domchek, S.M. (Susan), Dorfling, C.M. (Cecilia), Dörk, T. (Thilo), Dossus, L. (Laure), Duran, M. (Mercedes), Dürst, M. (Matthias), Dworniczak, B. (Bernd), Eccles, D. (Diana), Edwards, T. (Todd), Eeles, R. (Rosalind), Eilber, U. (Ursula), Ejlertsen, B. (Bent), Ekici, A.B. (Arif), Ellis, S. (Steve), Elvira, M. (Mingajeva), Eng, K.H. (Kevin H.), Engel, C. (Christoph), Evans, D.G. (Gareth), Fasching, P.A. (Peter), Ferguson, S. (Sarah), Ferrer, S.F., Flanagan, J.M. (James), Fogarty, Z.C. (Zachary C.), Fortner, R.T. (Renée T.), Fostira, F. (Florentia), Foulkes, W.D. (William D.), Fountzilas, G. (George), Fridley, B.L. (Brooke), Friebel, M.O.W. (Mark ), Friedman, E. (Eitan), Frost, D. (Debra), Ganz, P.A. (Patricia), Garber, J. (Judy), García, M.J. (María J.), Garcia-Barberan, V. (Vanesa), Gehrig, P.A. (Paola A.), Gentry-Maharaj, A. (Aleksandra), Gerdes, A-M. (Anne-Marie), Giles, G.G. (Graham G.), Glasspool, R. (Rosalind), Glendon, G. (Gord), Godwin, A.K. (Andrew K.), Radice, P. (Paolo), Goranova, T. (Teodora), Gore, M. (Martin), Greene, M.H. (Mark H.), Gronwald, J. (Jacek), Gruber, S.B. (Stephen), Hahnen, E. (Eric), Haiman, C.A. (Christopher), Håkansson, N. (Niclas), Hamann, U. (Ute), Hansen, T.V.O. (Thomas V.O.), Harrington, P.A. (Patricia A.), Harris, H.R. (Holly), Hauke, J. (Jan), Hein, A. (Alexander), Henderson, A. (Alex), Hildebrandt, M.A.T. (Michelle A.T.), Hillemanns, P. (Peter), Hodgson, S. (Shirley), Høgdall, C.K. (Claus), Høgdall, E. (Estrid), Hogervorst, F.B.L. (Frans B. L.), Holland, H. (Helene), Hooning, M.J. (Maartje J.), Hosking, K. (Karen), Huang, R.-Y. (Ruea-Yea), Hulick, P.J. (Peter), Hung, J. (Jillian), Hunter, D.J. (David J.), Huntsman, D.G. (David G.), Huzarski, T. (Tomasz), Imyanitov, E.N. (Evgeny), Isaacs, C. (Claudine), Iversen, E. (Erik), Izatt, L. (Louise), Izquierdo, A. (A.), Jakubowska, A. (Anna), James, P. (Paul), Janavicius, R. (Ramunas), Jernetz, M. (Mats), Jensen, A. (Allan), Jensen, U.B., John, E.M. (Esther), Johnatty, S.E. (Sharon), Jones, M.E. (Michael E.), Kannisto, P. (Päivi), Karlan, B.Y. (Beth), Karnezis, A. (Anthony), Kast, K. (Karin), Kennedy, C.J. (Catherine J.), Khusnutdinova, E.K. (Elza), Kiemeney, L.A.L.M. (Bart), Kiiski, J.I. (Johanna I.), Kim, S.-W. (Sung-Won), Kjaer, M. (Michael), Köbel, M. (Martin), Kopperud, R.K. (Reidun K.), Kruse, T.A. (Torben), Kupryjanczyk, J. (Jolanta), Kwong, A. (Ava), Laitman, Y. (Yael), Lambrechts, D. (Diether), Larrañaga, N. (Nerea), Larson, M.C. (Melissa), Lazaro, C. (Conxi), Le, N.D. (Nhu D.), Le Marchand, L. (Loic), Lee, J.W. (Jong Won), Lele, S.B. (Shashikant B.), Leminen, A. (Arto), Leroux, D. (Dominique), Lester, J. (Jenny), Lesueur, F. (Fabienne), Levine, D.A. (Douglas), Liang, D. (Dong), Liebrich, C. (Clemens), Lilyquist, J. (Jenna), Lipworth, L. (Loren), Lissowska, J. (Jolanta), Lu, K.H. (Karen), Lubinski, J. (Jan), Luccarini, C. (Craig), Lundvall, L. (Lene), Mai, P.L. (Phuong), Mendoza-Fandiño, G. (Gustavo), Manoukian, S. (Siranoush), Massuger, L.F. (Leon), May, T. (Taymaa), Mazoyer, S. (Sylvie), McAlpine, J.N. (Jessica N.), McGuire, V. (Valerie), McLaughlin, J. (John), McNeish, I. (Iain), Meijers-Heijboer, E.J. (Hanne), Meindl, A. (Alfons), Menon, U. (Usha), Mensenkamp, A.R. (Arjen R.), Merritt, M.A. (Melissa A.), Milne, R.L. (Roger), Mitchell, G. (Gillian), Modugno, F. (Francesmary), Moes-Sosnowska, J. (Joanna), Moffitt, M. (Melissa), Montagna, M. (Marco), Moysich, K.B. (Kirsten), Mulligan, A.M. (Anna Marie), Musinsky, J. (Jacob), Nathanson, K.L. (Katherine), Nedergaard, L. (Lotte), Ness, R.B. (Roberta), Neuhausen, S.L. (Susan), Nevanlinna, H. (Heli), Niederacher, D. (Dieter), Nussbaum, R. (Robert), Odunsi, K. (Kunle), Olah, E. (Edith), Olopade, O.I. (Olofunmilayo), Olsson, H. (Håkan), Olswold, C. (Curtis), O'Malley, D.M. (David M.), Ong, K.-R. (Kai-Ren), Onland-Moret, N.C. (Charlotte), Orr, N. (Nick), Orsulic, S. (Sandra), Osorio, A. (Ana), Palli, D. (Domenico), Papi, L. (Laura), Park-Simon, T.-W., Paul, J. (James), Pearce, C.L. (Celeste), Pedersen, I.S. (Inge Søkilde), Peeters, P.H.M., Peissel, B. (Bernard), Peixoto, A. (Ana), Pejovic, T. (Tanja), Pelttari, L.M. (Liisa M.), Permuth, J.B. (Jennifer B.), Peterlongo, P. (Paolo), Pezzani, L. (Lidia), Pfeiler, G. (Georg), Phillips, K.-A. (Kelly-Anne), Piedmonte, M. (Marion), Pike, M.C. (Malcolm), Piskorz, A.M. (Anna M.), Poblete, S.R. (Samantha R.), Pócza, T. (Tímea), Poole, E.M. (Elizabeth M.), Poppe, B. (Bruce), Porteous, M.E. (Mary), Prieur, F. (Fabienne), Prokofyeva, D. (Darya), Pugh, E. (Elizabeth), Pujana, M.A. (Miquel Angel), Pujol, P. (Pascal), Rantala, J. (Johanna), Rappaport-Fuerhauser, C. (Christine), Rennert, G. (Gad), Rhiem, K. (Kerstin), Rice, P. (Patricia), Richardson, A.L. (Andrea), Robson, M. (Mark), Rodriguez, G.C. (Gustavo), Rodríguez-Antona, C. (Cristina), Romm, J. (Jane), Rookus, M.A. (Matti), Rossing, M.A. (Mary Anne), Rothstein, J.H. (Joseph H.), Rudolph, A. (Anja), Runnebaum, I.B. (Ingo), Salvesen, H.B. (Helga), Sandler, D.P. (Dale P.), Schoemaker, M.J. (Minouk J.), Senter, L. (Leigha), Setiawan, V.W. (V. Wendy), Severi, G. (Gianluca), Sharma, P. (Priyanka), Shelford, T. (Tameka), Siddiqui, N. (Nadeem), Side, L. (Lucy), Sieh, W. (Weiva), Singer, C.F. (Christian), Sobol, H. (Hagay), Song, H. (Honglin), Southey, M.C. (Melissa), Spurdle, A.B. (Amanda), Stadler, Z. (Zsofia), Steinemann, D. (Doris), Stoppa-Lyonnet, D. (Dominique), Sucheston-Campbell, L.E. (Lara E.), Sukiennicki, G. (Grzegorz), Sutphen, R. (Rebecca), Sutter, C. (Christian), Swerdlow, A.J. (Anthony ), Szabo, C. (Csilla), Szafron, L. (Lukasz), Tan, Y.Y. (Yen Y.), Taylor, J.A. (Jack A.), Tea, M.-K., Teixeira, P.J., Teo, S.-H. (Soo-Hwang), Terry, K.L. (Kathryn L.), Thompson, P.J. (Pamela J.), Thomsen, L.C.V. (Liv Cecilie Vestrheim), Thull, D.L. (Darcy L.), Tihomirova, L. (Laima), Tinker, A.V. (Anna V.), Tischkowitz, M. (Marc), Tognazzo, S. (Silvia), Toland, A.E. (Amanda Ewart), Tone, A. (Alicia), Trabert, B. (Britton), Travis, S.P.L. (Simon), Trichopoulou, A. (Antonia), Tung, N. (Nadine), Tworoger, S. (Shelley), Van Altena, A.M. (Anne M.), Van Den Berg, D. (David), Van Der Hout, A.H. (Annemarie H.), Luijt, R.B. (Rob) van der, Van Heetvelde, M. (Mattias), Van Nieuwenhuysen, E. (Els), Rensburg, E.J. (Elizabeth) van, Vanderstichele, A. (Adriaan), Varon-Mateeva, R. (Raymonda), Vega, A. (Ana), Edwards, D.V. (Digna Velez), Vergote, I., Vierkant, R.A. (Robert), Vijai, J. (Joseph), Vratimos, A. (Athanassios), Walker, L.J. (Lisa), Walsh, C. (Christine), Wand, D. (Dorothea), Wang-Gohrke, S. (Shan), Wappenschmidt, B. (Barbara), Webb, P.M. (Penelope M.), Weinberg, C.R. (Clarice R.), Weitzel, J.N. (Jeffrey), Wentzensen, N. (N.), Whittemore, A.S. (Alice), Wijnen, J.T. (Juul), Wilkens, L.R. (Lynne), Wolk, K. (Kerstin), Woo, M. (Michelle), Wu, X. (Xifeng), Wu, A.H. (Anna), Yang, H.P. (Hannah), Yannoukakos, D. (Drakoulis), Ziogas, A. (Argyrios), Zorn, K.K. (Kristin K.), Narod, S.A. (Steven A.), Easton, D.F. (Douglas), Amos, W., Schildkraut, J.M. (Joellen), Ramus, S.J. (Susan), Ottini, L. (Laura), Goodman, M.T. (Marc), Park, S.K. (Sue K.), Kelemen, L.E. (Linda), Risch, H. (Harvey), Thomassen, M. (Mads), Offit, K. (Kenneth), Simard, J. (Jacques), Schmutzler, R.K. (Rita), Hazelett, D. (Dennis), Monteiro, A.N.A. (Alvaro N.), Couch, F.J. (Fergus), Berchuck, A. (Andrew), Chenevix-Trench, G. (Georgia), Goode, E.L. (Ellen), Sellers, T.F., Gayther, S.A. (Simon), Antoniou, A.C. (Antonis), Pharoah, P.D.P. (Paul), Phelan, C. (Catherine), Kuchenbaecker, K.B. (Karoline), Tyrer, J.P. (Jonathan P.), Kar, S.P. (Siddhartha P.), Lawrenson, K. (Kate), Winham, S.J. (Stacey J.), Dennis, J. (Joe), Pirie, A. (Ailith), Riggan, M.J. (Marjorie J.), Chornokur, G. (Ganna), Earp, M.A. (Madalene A.), Lyra, P.C. (Paulo C.), Lee, J.M. (Janet M.), Coetzee, S. (Simon), Beesley, J. (Jonathan), McGuffog, L. (Lesley), Soucy, P. (Penny), Dicks, E. (Ed), Lee, A. (Andrew), Barrowdale, D. (Daniel), Lecarpentier, J. (Julie), Leslie, G. (Goska), Aalfs, C.M. (Cora), Aben, K.K.H. (Katja), Adams, M. (Marcia), Adlard, J.W. (Julian), Andrulis, I.L. (Irene), Anton-Culver, H. (Hoda), Antonenkova, N. (Natalia), Aravantinos, G. (Gerasimos), Arnold, N. (Norbert), Arun, B.K. (Banu), Arver, B. (Brita), Azzollini, J., Balmana, J. (Judith), Banerjee, S. (Susana), Barjhoux, L. (Laure), Barkardottir, R.B. (Rosa B.), Bean, Y. (Yukie), Beckmann, M.W. (Matthias), Beeghly-Fadiel, A. (Alicia), Benítez, J. (Javier), Bermisheva, M. (Marina), Bernardini, M.Q. (Marcus Q.), Birrer, M.J. (Michael J.), Bjorge, L. (Line), Black, A., Blankstein, K. (Kenneth), Blok, M.J. (Marinus), Bodelon, C. (Clara), Bogdanova, N. (Natalia), Bojesen, A. (Anders), Bonanni, B. (Bernardo), Borg, Å. (Åke), Bradbury, A.R. (Angela R.), Brenton, J.D. (James D.), Brewer, C. (Carole), Brinton, L.A. (Louise), Broberg, P. (Per), Brooks-Wilson, A. (Angela), Bruinsma, F. (Fiona), Brunet, J. (Joan), Buecher, B. (Bruno), Butzow, R. (Ralf), Buys, S.S. (Saundra), Caldes, T. (Trinidad), Caligo, M.A. (Maria A.), Campbell, I. (Ian), Cannioto, R. (Rikki), Carney, M.E. (Michael), Cescon, T. (Terence), Chan, S. (Salina), Chang-Claude, J. (Jenny), Chanock, S.J. (Stephen), Chen, X.Q. (Xiao Qing), Chiew, Y.-E. (Yoke-Eng), Chiquette, J. (Jocelyne), Chung, W. (Wendy), Claes, K. (Kathleen), Conner, T. (Thomas), Cook, L.S. (Linda S.), Cook, J. (Jackie), Cramer, D.W. (Daniel), Cunningham, J.M. (Julie), D'Aloisio, A.A. (Aimee A.), Daly, M.B. (Mary), Damiola, F. (Francesca), Damirovna, S.D. (Sakaeva Dina), Dansonka-Mieszkowska, A. (Agnieszka), Dao, F. (Fanny), Davidson, R. (Rosemarie), DeFazio, A. (Anna), Delnatte, C.D. (Capucine), Doheny, K.F. (Kimberly), Díez, O. (Orland), Ding, Y.C. (Yuan Chun), Doherty, J.A. (Jennifer), Domchek, S.M. (Susan), Dorfling, C.M. (Cecilia), Dörk, T. (Thilo), Dossus, L. (Laure), Duran, M. (Mercedes), Dürst, M. (Matthias), Dworniczak, B. (Bernd), Eccles, D. (Diana), Edwards, T. (Todd), Eeles, R. (Rosalind), Eilber, U. (Ursula), Ejlertsen, B. (Bent), Ekici, A.B. (Arif), Ellis, S. (Steve), Elvira, M. (Mingajeva), Eng, K.H. (Kevin H.), Engel, C. (Christoph), Evans, D.G. (Gareth), Fasching, P.A. (Peter), Ferguson, S. (Sarah), Ferrer, S.F., Flanagan, J.M. (James), Fogarty, Z.C. (Zachary C.), Fortner, R.T. (Renée T.), Fostira, F. (Florentia), Foulkes, W.D. (William D.), Fountzilas, G. (George), Fridley, B.L. (Brooke), Friebel, M.O.W. (Mark ), Friedman, E. (Eitan), Frost, D. (Debra), Ganz, P.A. (Patricia), Garber, J. (Judy), García, M.J. (María J.), Garcia-Barberan, V. (Vanesa), Gehrig, P.A. (Paola A.), Gentry-Maharaj, A. (Aleksandra), Gerdes, A-M. (Anne-Marie), Giles, G.G. (Graham G.), Glasspool, R. (Rosalind), Glendon, G. (Gord), Godwin, A.K. (Andrew K.), Radice, P. (Paolo), Goranova, T. (Teodora), Gore, M. (Martin), Greene, M.H. (Mark H.), Gronwald, J. (Jacek), Gruber, S.B. (Stephen), Hahnen, E. (Eric), Haiman, C.A. (Christopher), Håkansson, N. (Niclas), Hamann, U. (Ute), Hansen, T.V.O. (Thomas V.O.), Harrington, P.A. (Patricia A.), Harris, H.R. (Holly), Hauke, J. (Jan), Hein, A. (Alexander), Henderson, A. (Alex), Hildebrandt, M.A.T. (Michelle A.T.), Hillemanns, P. (Peter), Hodgson, S. (Shirley), Høgdall, C.K. (Claus), Høgdall, E. (Estrid), Hogervorst, F.B.L. (Frans B. L.), Holland, H. (Helene), Hooning, M.J. (Maartje J.), Hosking, K. (Karen), Huang, R.-Y. (Ruea-Yea), Hulick, P.J. (Peter), Hung, J. (Jillian), Hunter, D.J. (David J.), Huntsman, D.G. (David G.), Huzarski, T. (Tomasz), Imyanitov, E.N. (Evgeny), Isaacs, C. (Claudine), Iversen, E. (Erik), Izatt, L. (Louise), Izquierdo, A. (A.), Jakubowska, A. (Anna), James, P. (Paul), Janavicius, R. (Ramunas), Jernetz, M. (Mats), Jensen, A. (Allan), Jensen, U.B., John, E.M. (Esther), Johnatty, S.E. (Sharon), Jones, M.E. (Michael E.), Kannisto, P. (Päivi), Karlan, B.Y. (Beth), Karnezis, A. (Anthony), Kast, K. (Karin), Kennedy, C.J. (Catherine J.), Khusnutdinova, E.K. (Elza), Kiemeney, L.A.L.M. (Bart), Kiiski, J.I. (Johanna I.), Kim, S.-W. (Sung-Won), Kjaer, M. (Michael), Köbel, M. (Martin), Kopperud, R.K. (Reidun K.), Kruse, T.A. (Torben), Kupryjanczyk, J. (Jolanta), Kwong, A. (Ava), Laitman, Y. (Yael), Lambrechts, D. (Diether), Larrañaga, N. (Nerea), Larson, M.C. (Melissa), Lazaro, C. (Conxi), Le, N.D. (Nhu D.), Le Marchand, L. (Loic), Lee, J.W. (Jong Won), Lele, S.B. (Shashikant B.), Leminen, A. (Arto), Leroux, D. (Dominique), Lester, J. (Jenny), Lesueur, F. (Fabienne), Levine, D.A. (Douglas), Liang, D. (Dong), Liebrich, C. (Clemens), Lilyquist, J. (Jenna), Lipworth, L. (Loren), Lissowska, J. (Jolanta), Lu, K.H. (Karen), Lubinski, J. (Jan), Luccarini, C. (Craig), Lundvall, L. (Lene), Mai, P.L. (Phuong), Mendoza-Fandiño, G. (Gustavo), Manoukian, S. (Siranoush), Massuger, L.F. (Leon), May, T. (Taymaa), Mazoyer, S. (Sylvie), McAlpine, J.N. (Jessica N.), McGuire, V. (Valerie), McLaughlin, J. (John), McNeish, I. (Iain), Meijers-Heijboer, E.J. (Hanne), Meindl, A. (Alfons), Menon, U. (Usha), Mensenkamp, A.R. (Arjen R.), Merritt, M.A. (Melissa A.), Milne, R.L. (Roger), Mitchell, G. (Gillian), Modugno, F. (Francesmary), Moes-Sosnowska, J. (Joanna), Moffitt, M. (Melissa), Montagna, M. (Marco), Moysich, K.B. (Kirsten), Mulligan, A.M. (Anna Marie), Musinsky, J. (Jacob), Nathanson, K.L. (Katherine), Nedergaard, L. (Lotte), Ness, R.B. (Roberta), Neuhausen, S.L. (Susan), Nevanlinna, H. (Heli), Niederacher, D. (Dieter), Nussbaum, R. (Robert), Odunsi, K. (Kunle), Olah, E. (Edith), Olopade, O.I. (Olofunmilayo), Olsson, H. (Håkan), Olswold, C. (Curtis), O'Malley, D.M. (David M.), Ong, K.-R. (Kai-Ren), Onland-Moret, N.C. (Charlotte), Orr, N. (Nick), Orsulic, S. (Sandra), Osorio, A. (Ana), Palli, D. (Domenico), Papi, L. (Laura), Park-Simon, T.-W., Paul, J. (James), Pearce, C.L. (Celeste), Pedersen, I.S. (Inge Søkilde), Peeters, P.H.M., Peissel, B. (Bernard), Peixoto, A. (Ana), Pejovic, T. (Tanja), Pelttari, L.M. (Liisa M.), Permuth, J.B. (Jennifer B.), Peterlongo, P. (Paolo), Pezzani, L. (Lidia), Pfeiler, G. (Georg), Phillips, K.-A. (Kelly-Anne), Piedmonte, M. (Marion), Pike, M.C. (Malcolm), Piskorz, A.M. (Anna M.), Poblete, S.R. (Samantha R.), Pócza, T. (Tímea), Poole, E.M. (Elizabeth M.), Poppe, B. (Bruce), Porteous, M.E. (Mary), Prieur, F. (Fabienne), Prokofyeva, D. (Darya), Pugh, E. (Elizabeth), Pujana, M.A. (Miquel Angel), Pujol, P. (Pascal), Rantala, J. (Johanna), Rappaport-Fuerhauser, C. (Christine), Rennert, G. (Gad), Rhiem, K. (Kerstin), Rice, P. (Patricia), Richardson, A.L. (Andrea), Robson, M. (Mark), Rodriguez, G.C. (Gustavo), Rodríguez-Antona, C. (Cristina), Romm, J. (Jane), Rookus, M.A. (Matti), Rossing, M.A. (Mary Anne), Rothstein, J.H. (Joseph H.), Rudolph, A. (Anja), Runnebaum, I.B. (Ingo), Salvesen, H.B. (Helga), Sandler, D.P. (Dale P.), Schoemaker, M.J. (Minouk J.), Senter, L. (Leigha), Setiawan, V.W. (V. Wendy), Severi, G. (Gianluca), Sharma, P. (Priyanka), Shelford, T. (Tameka), Siddiqui, N. (Nadeem), Side, L. (Lucy), Sieh, W. (Weiva), Singer, C.F. (Christian), Sobol, H. (Hagay), Song, H. (Honglin), Southey, M.C. (Melissa), Spurdle, A.B. (Amanda), Stadler, Z. (Zsofia), Steinemann, D. (Doris), Stoppa-Lyonnet, D. (Dominique), Sucheston-Campbell, L.E. (Lara E.), Sukiennicki, G. (Grzegorz), Sutphen, R. (Rebecca), Sutter, C. (Christian), Swerdlow, A.J. (Anthony ), Szabo, C. (Csilla), Szafron, L. (Lukasz), Tan, Y.Y. (Yen Y.), Taylor, J.A. (Jack A.), Tea, M.-K., Teixeira, P.J., Teo, S.-H. (Soo-Hwang), Terry, K.L. (Kathryn L.), Thompson, P.J. (Pamela J.), Thomsen, L.C.V. (Liv Cecilie Vestrheim), Thull, D.L. (Darcy L.), Tihomirova, L. (Laima), Tinker, A.V. (Anna V.), Tischkowitz, M. (Marc), Tognazzo, S. (Silvia), Toland, A.E. (Amanda Ewart), Tone, A. (Alicia), Trabert, B. (Britton), Travis, S.P.L. (Simon), Trichopoulou, A. (Antonia), Tung, N. (Nadine), Tworoger, S. (Shelley), Van Altena, A.M. (Anne M.), Van Den Berg, D. (David), Van Der Hout, A.H. (Annemarie H.), Luijt, R.B. (Rob) van der, Van Heetvelde, M. (Mattias), Van Nieuwenhuysen, E. (Els), Rensburg, E.J. (Elizabeth) van, Vanderstichele, A. (Adriaan), Varon-Mateeva, R. (Raymonda), Vega, A. (Ana), Edwards, D.V. (Digna Velez), Vergote, I., Vierkant, R.A. (Robert), Vijai, J. (Joseph), Vratimos, A. (Athanassios), Walker, L.J. (Lisa), Walsh, C. (Christine), Wand, D. (Dorothea), Wang-Gohrke, S. (Shan), Wappenschmidt, B. (Barbara), Webb, P.M. (Penelope M.), Weinberg, C.R. (Clarice R.), Weitzel, J.N. (Jeffrey), Wentzensen, N. (N.), Whittemore, A.S. (Alice), Wijnen, J.T. (Juul), Wilkens, L.R. (Lynne), Wolk, K. (Kerstin), Woo, M. (Michelle), Wu, X. (Xifeng), Wu, A.H. (Anna), Yang, H.P. (Hannah), Yannoukakos, D. (Drakoulis), Ziogas, A. (Argyrios), Zorn, K.K. (Kristin K.), Narod, S.A. (Steven A.), Easton, D.F. (Douglas), Amos, W., Schildkraut, J.M. (Joellen), Ramus, S.J. (Susan), Ottini, L. (Laura), Goodman, M.T. (Marc), Park, S.K. (Sue K.), Kelemen, L.E. (Linda), Risch, H. (Harvey), Thomassen, M. (Mads), Offit, K. (Kenneth), Simard, J. (Jacques), Schmutzler, R.K. (Rita), Hazelett, D. (Dennis), Monteiro, A.N.A. (Alvaro N.), Couch, F.J. (Fergus), Berchuck, A. (Andrew), Chenevix-Trench, G. (Georgia), Goode, E.L. (Ellen), Sellers, T.F., Gayther, S.A. (Simon), Antoniou, A.C. (Antonis), and Pharoah, P.D.P. (Paul)
Abstract: To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC.
Published: 2017
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40. BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Author: Meeks, H.D., Song, H.L., Michailidou, K., Bolla, M.K., Dennis, J., Wang, Q., Barrowdale, D., Frost, D., McGuffog, L., Ellis, S., Feng, B.J., Buys, S.S., Hopper, J.L., Southey, M.C., Tesoriero, A., James, P.A., Bruinsma, F., Campbell, I.G., Broeks, A., Schmidt, M.K., Hogervorst, F.B.L., Beckman, M.W., Fasching, P.A., Fletcher, O., Johnson, N., Sawyer, E.J., Riboli, E., Banerjee, S., Menon, U., Tomlinson, I., Burwinkel, B., Hamann, U., Marme, F., Rudolph, A., Janavicius, R., Tihomirova, L., Tung, N., Garber, J., Cramer, D., Terry, K.L., Poole, E.M., Tworoger, S.S., Dorfling, C.M., Rensburg, E.J. van, Godwin, A.K., Guenel, P., Truong, T., Stoppa-Lyonnet, D., Damiola, F., Mazoyer, S., Sinilnikova, O.M., Isaacs, C., Maugard, C., Bojesen, S.E., Flyger, H., Gerdes, A.M., Hansen, T.V.O., Jensen, A., Kjaer, S.K., Hogdall, C., Hogdall, E., Pedersen, I.S., Thomassen, M., Benitez, J., Gonzalez-Neira, A., Osorio, A., Hoya, M. de la, Segura, P.P., Diez, O., Lazaro, C., Brunet, J., Anton-Culver, H., Eunjung, L., John, E.M., Neuhausen, S.L., Ding, Y.C., Castillo, D., Weitzel, J.N., Ganz, P.A., Nussbaum, R.L., Chan, S.B., Karlan, B.Y., Lester, J., Wu, A., Gayther, S., Ramus, S.J., Sieh, W., Whittermore, A.S., Monteiro, A.N.A., Phelan, C.M., Terry, M.B., Piedmonte, M., Offit, K., Robson, M., Levine, D., Moysich, K.B., Cannioto, R., Olson, S.H., Daly, M.B., Nathanson, K.L., Domchek, S.M., Lu, K.H., Liang, D., Hildebrant, M.A.T., Ness, R., Modugno, F., Pearce, L., Goodman, M.T., Thompson, P.J., Brenner, H., Butterbach, K., Meindl, A., Hahnen, E., Wappenschmidt, B., Brauch, H., Bruning, T., Blomqvist, C., Khan, S., Nevanlinna, H., Pelttari, L.M., Aittomaki, K., Butzow, R., Bogdanova, N.V., Dork, T., Lindblom, A., Margolin, S., Rantala, J., Kosma, V.M., Mannermaa, A., Lambrechts, D., Neven, P., Claes, K.B.M., Maerken, T. van, Chang-Claude, J., Flesch-Janys, D., Heitz, F., Varon-Mateeva, R., Peterlongo, P., Radice, P., Viel, A., Barile, M., Peissel, B., Manoukian, S., Montagna, M., Oliani, C., Peixoto, A., Teixeira, M.R., Collavoli, A., Hallberg, E., Olson, J.E., Goode, E.L., Hart, S.N., Shimelis, H., Cunningham, J.M., Giles, G.G., Milne, R.L., Healey, S., Tucker, K., Haiman, C.A., Henderson, B.E., Goldberg, M.S., Tischkowitz, M., Simard, J., Soucy, P., Eccles, D.M., N. le, Borresen-Dale, A.L., Kristensen, V., Salvesen, H.B., Bjorge, L., Bandera, E.V., Risch, H., Zheng, W., Beeghly-Fadiel, A., Cai, H., Pylkas, K., Tollenaar, R.A.E.M., Ouweland, A.M.W. van der, Andrulis, I.L., Knight, J.A., Narod, S., Devilee, P., Winqvist, R., Figueroa, J., Greene, M.H., Mai, P.L., Loud, J.T., Garcia-Closas, M., Schoemaker, M.J., Czene, K., Darabi, H., McNeish, I., Siddiquil, N., Glasspool, R., Kwong, A., Park, S.K., Teo, S.H., Yoon, S.Y., Matsuo, K., Hosono, S., Woo, Y.L., Gao, Y.T., Foretova, L., Singer, C.F., Rappaport-Feurhauser, C., Friedman, E., Laitman, Y., Rennert, G., Imyanitov, E.N., Hulick, P.J., Olopade, O.I., Senter, L., Olah, E., Doherty, J.A., Schildkraut, J., Koppert, L.B., Kiemeney, L.A., Massuger, L.F.A.G., Cook, L.S., Pejovic, T., Li, J.M., Borg, A., Ofverholm, A., Rossing, M.A., Wentzensen, N., Henriksson, K., Cox, A., Cross, S.S., Pasini, B.J., Shah, M., Kabisch, M., Torres, D., Jakubowska, A., Lubinski, J., Gronwald, J., Agnarsson, B.A., Kupryjanczyk, J., Moes-Sosnowska, J., Fostira, F., Konstantopoulou, I., Slager, S., Jones, M., Antoniou, A.C., Berchuck, A., Swerdlow, A., Chenevix-Trench, G., Dunning, A.M., Pharoah, P.D.P., Hall, P., Easton, D.F., Couch, F.J., Spurdle, A.B., Goldgar, D.E., EMBRACE, kConFab Investigators, Australia Ovarian Canc Study Grp, HEBON, GEMO Study Collaborators, OCGN, PRostate Canc Assoc Grp, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Targeted Gynaecologic Oncology (TARGON), Clinical Genetics, Obstetrics & Gynecology, Surgery, and [ 1 ] Univ Utah, Huntsman Canc Inst, Canc Control & Populat Sci, Salt Lake City, UT USA [ 2 ] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England [ 3 ] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England [ 4 ] Univ Utah, Sch Med, Huntsman Canc Inst, Dept Dermatol, 2000 Circle Hope Dr, Salt Lake City, UT 84112 USA [ 5 ] Univ Utah, Sch Med, Dept Med, Huntsman Canc Inst, Salt Lake City, UT USA [ 6 ] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic, Australia [ 7 ] Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia [ 8 ] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Parkville, Vic 3052, Australia [ 9 ] KConFab Kathleen Cuningham Consortium Res Familia, Peter MacCallum Canc Ctr, Melbourne, Vic, Australia [ 10 ] Peter MacCallum Canc Ctr, Familial Canc Ctr, Melbourne, Vic, Australia [ 11 ] Univ Melbourne, Dept Oncol, Melbourne, Vic, Australia [ 12 ] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia [ 13 ] Univ Melbourne, Peter MacCallum Canc Ctr, Sir Peter MacCallum Dept Oncol, Parkville, Vic 3052, Australia [ 14 ] QIMR Berghofer Med Res Inst, Canc Div, Brisbane, Qld, Australia [ 15 ] Peter MacCallum Canc Inst, East Melbourne, Vic, Australia [ 16 ] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Amsterdam, Netherlands [ 17 ] Netherlands Canc Inst, Family Canc Clin, Amsterdam, Netherlands [ 18 ] Netherlands Canc Inst, Hereditary Breast & Ovarian Canc Res Grp Netherla, Coordinating Ctr, Amsterdam, Netherlands [ 19 ] Univ Erlangen Nurnberg, Comprehens Canc Ctr Erlangen EMN, Univ Hosp Erlangen, Dept Gynaecol & Ostetr, D-91054 Erlangen, Germany [ 20 ] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA [ 21 ] Inst Canc Res, Div Breast Canc Res, London SW3 6JB, England [ 22 ] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England [ 23 ] Guys Hosp, Kings Coll London, Div Canc Studies, Res Oncol, London SE1 9RT, England [ 24 ] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England [ 25 ] Royal Marsden NHS Fdn Trust, London, England [ 26 ] Univ Coll London Elizabeth Garrett Anderson EGA, Inst Womens Hlth, Womens Canc, London, England [ 27 ] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England [ 28 ] Univ Oxford, Oxford Biomed Res Ctr, Oxford, England [ 29 ] German Canc Res Ctr, Div Mol Genet Epidemiol, Heidelberg, Germany [ 30 ] German Canc Res Ctr, Mol Genet Breast Canc, Heidelberg, Germany [ 31 ] Heidelberg Univ, Dept Obstet & Gynecol, Heidelberg, Germany [ 32 ] Heidelberg Univ, Natl Ctr Tumor Dis, Heidelberg, Germany [ 33 ] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany [ 34 ] State Res Inst Ctr Innovat Med, Vilnius, Lithuania [ 35 ] Latvian Biomed Res & Study Ctr, Riga, Latvia [ 36 ] Beth Israel Deaconess Med Ctr, Dept Med Oncol, Boston, MA 02215 USA [ 37 ] Dana Farber Canc Inst, Canc Risk & Prevent Clin, Boston, MA 02115 USA [ 38 ] Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, 75 Francis St, Boston, MA 02115 USA [ 39 ] Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA [ 40 ] Harvard Univ, Sch Med, Boston, MA 02115 USA [ 41 ] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 665 Huntington Ave, Boston, MA 02115 USA [ 42 ] Univ Pretoria, Dept Genet, ZA-0002 Pretoria, South Africa [ 43 ] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66103 USA [ 44 ] Natl Inst Hlth & Med Res, Ctr Res Epidemiol & Populat Hlth CESP, Environm Epidemiol Canc, INSERM,U1018, Villejuif, France [ 45 ] Univ Paris Sud, Villejuif, France [ 46 ] UNICANCER Genet Grp, GEMO Study Natl Canc Genet Network, Paris, France [ 47 ] Inst Curie, Dept Tumour Biol, Paris, France [ 48 ] INSERM, U830, Inst Curie, Paris, France [ 49 ] Univ Paris 05, Sorbonne Paris Cite, Paris, France [ 50 ] Univ Lyon, Ctr Rech Cancerol Lyon, INSERM,U1052, CNRS UMR 5286, Lyon, France [ 51 ] Hosp Civils Pyon, Ctr Leon Berard, Unite Mixte Genet Constitutionelle Canc Frequents, Lyon, France [ 52 ] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA [ 53 ] Hop Univ Strasbourg, CHRU Nouvel, Lab Diagnost Genet, Hop Civil, Strasbourg, France [ 54 ] Hop Univ Strasbourg, CHRU Nouvel, Serv Oncohematol, Hop Civil, Strasbourg, France [ 55 ] Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark [ 56 ] Copenhagen Univ Hosp, Dept Clin Biochem, Herlev Hosp, Herlev, Denmark [ 57 ] Copenhagen Univ Hosp, Herlev Hosp, Dept Breast Surg, Herlev, Denmark [ 58 ] Copenhagen Univ Hosp, Rigshosp, Dept Clin Genet, Copenhagen, Denmark [ 59 ] Copenhagen Univ Hosp, Rigshosp, Ctr Genom Med, Copenhagen, Denmark [ 60 ] Danish Canc Soc, Dept Virus Lifestyle & Genes, Res Ctr, Copenhagen, Denmark [ 61 ] Univ Copenhagen, Rigshosp, Dept Gynecol, DK-2100 Copenhagen, Denmark [ 62 ] Univ Copenhagen, Herlev Hosp, Dept Pathol, Mol Unit, Copenhagen, Denmark [ 63 ] Aalborg Univ Hosp, Dept Biochem, Sect Mol Diagnost, Aalborg, Denmark [ 64 ] Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense C, Denmark [ 65 ] Spanish 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Epidemiol, Fremont, CA USA [ 77 ] Beckman Res Inst City Hope, Dept Populat Sci, Duarte, CA USA [ 78 ] City Hope Clin Canc Genet Community Res Network, Clin Canc Genet, Duarte, CA USA [ 79 ] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Sch Med, Div Canc Prevent & Control Res, Los Angeles, CA 90024 USA [ 80 ] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Sch Publ Hlth, Div Canc Prevent & Control Res, Los Angeles, CA 90024 USA [ 81 ] Univ Calif San Francisco, Dept Med & Genet, San Francisco, CA 94143 USA [ 82 ] Univ Calif San Francisco, Helen Diller Family Canc Ctr, Canc Risk Program, San Francisco, CA 94143 USA [ 83 ] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA 90048 USA [ 84 ] Stanford Univ, Dept Hlth Res & Policy Epidemiol, Stanford, CA USA [ 85 ] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Canc Epidemiol, Tampa, FL 33682 USA [ 86 ] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA [ 87 ] Roswell Pk Ctr Inst, NRG Oncol Stat & Data Management Ctr, Buffalo, NY USA [ 88 ] Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10021 USA [ 89 ] Mem Sloan Kettering Canc Ctr, Dept Surg, Gynecol Serv, 1275 York Ave, New York, NY 10021 USA [ 90 ] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA [ 91 ] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, 1275 York Ave, New York, NY 10021 USA [ 92 ] Fox Chase Canc Ctr, Dept Clin Genet, 7701 Burholme Ave, Philadelphia, PA 19111 USA [ 93 ] Univ Penn, Perelman Sch Med, Abramson Canc Ctr, Basser Ctr, Philadelphia, PA 19104 USA [ 94 ] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA [ 95 ] Texas So Univ, Coll Pharm & Hlth Sci, Houston, TX 77004 USA [ 96 ] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA [ 97 ] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA [ 98 ] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA [ 99 ] Univ 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Hosp Cologne, Ctr Familial Breast & Ovarian Canc, Cologne, Germany [ 112 ] Univ Hosp Cologne, Dept Obstet & Gynaecol, Cologne, Germany [ 113 ] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Auerbachstr 112, Stuttgart, Germany [ 114 ] Univ Tubingen, Tubingen, Germany [ 115 ] Ruhr Univ Bochum IPA, German Social Accid Insurance & Inst, Inst Prevent & Occupat Med, Bochum, Germany [ 116 ] Univ Helsinki, Dept Oncol, Helsinki, Finland [ 117 ] Helsinki Univ Hosp, Helsinki, Finland [ 118 ] Univ Helsinki, Dept Obstet & Gynecol, Helsinki, Finland [ 119 ] Univ Helsinki, Dept Clin Genet, Helsinki, Finland [ 120 ] Univ Helsinki, Dept Pathol, Helsinki, Finland [ 121 ] Hannover Med Sch, Gynaecol Res Unit, Hannover, Germany [ 122 ] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden [ 123 ] Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden [ 124 ] Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden [ 125 ] Univ Eastern Finland, Inst Clin Med Pathol & Forens Med, Sch Med, Kuopio, Finland [ 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Canada [ 154 ] McGill Univ, Dept Oncol, Program Canc Genet, Montreal, PQ, Canada [ 155 ] Univ Cambridge, Sch Med, Cambridge, England [ 156 ] Ctr Hosp Univ Quebec, Res Ctr, Quebec City, PQ, Canada [ 157 ] Univ Laval, Quebec City, PQ, Canada [ 158 ] Univ Southampton, Fac Med, Southampton SO9 5NH, Hants, England [ 159 ] BC Canc Agcy, Canc Control Res, Vancouver, BC, Canada [ 160 ] Oslo Univ Hosp, Radiumhosp, Inst Canc Res, Dept Genet, Oslo, Norway [ 161 ] Univ Oslo, Fac Med, Inst Clin Med, Oslo, Norway [ 162 ] Univ Oslo, Oslo Univ Hosp, Dept Clin Mol Biol, Oslo, Norway [ 163 ] Haukeland Hosp, Dept Gynecol & Obstet, N-5021 Bergen, Norway [ 164 ] Univ Bergen, Dept Clin Sci, Ctr Canc Biomarkers, Bergen, Norway [ 165 ] Rutgers Canc Inst New Jersey, New Brunswick, NJ USA [ 166 ] Yale Univ, Sch Publ Hlth, Dept Chron Dis Epidemiol, New Haven, CT USA [ 167 ] Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr,Vanderbilt Ingram Canc C, Div Epidemiol,Dept Med, 221 Kirkland Hall, Nashville, TN 37235 USA [ 168 ] Univ Oulu, Dept Clin Chem, Lab Canc Genet & Tumor Biol, Oulu, Finland [ 169 ] Univ Oulu, Bioctr Oulu, Oulu, Finland [ 170 ] Northern Finland Lab Ctr Nordlab, Lab Canc Genet & Tumor Biol, Oulu, Finland [ 171 ] Erasmus Univ, Med Ctr, Dept Surg Oncol, Rotterdam, Netherlands [ 172 ] Erasmus Univ, Med Ctr, Dept Clin Genet, Family Canc Clin, Rotterdam, Netherlands [ 173 ] Mt Sinai Hosp, Lunenfeld Res Inst, Ontario Canc Genet Network, Fred A Litwin Ctr Canc Genet, Toronto, ON M5G 1X5, Canada [ 174 ] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada [ 175 ] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Prosserman Ctr Hlth Res, Toronto, ON M5G 1X5, Canada [ 176 ] Univ Toronto, Dalla Lana Sch Publ Hlth, Div Epidemiol, Toronto, ON, Canada [ 177 ] Univ Toronto, Womens Coll, Res Inst, Toronto, ON, Canada [ 178 ] Leiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands [ 179 ] Leiden Univ, Med Ctr, Dept Pathol, Leiden, Netherlands [ 180 ] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA [ 181 ] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA [ 182 ] Inst Canc Res, Div Genet & Epidemiol, London SW3 6JB, England [ 183 ] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden [ 184 ] Univ Glasgow, Beatson Inst Canc Res, Wolfson Wohl Canc Res Ctr, Inst Canc Sci, Glasgow, Lanark, Scotland [ 185 ] Glasgow Royal Infirm, Dept Gynaecol Oncol, Glasgow G4 0SF, Lanark, Scotland [ 186 ] Beatson West Scotland Canc Ctr, Canc Res UK Clin Trials Unit, Glasgow, Lanark, Scotland [ 187 ] Hong Kong Sanat & Hosp, Canc Genet Ctr, Hong Kong Hereditary Breast Canc Family Registry, Hong Kong, Hong Kong, Peoples R China [ 188 ] Univ Hong Kong, Dept Surg, Hong Kong, Hong Kong, Peoples R China [ 189 ] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea [ 190 ] Seoul Natl Univ, Coll Med, Dept Biomed Sci, Seoul, South Korea [ 191 ] Seoul Natl Univ, Coll Med, Canc Res Inst, Seoul, South Korea [ 192 ] Sime Darby Med Ctr, Canc Res Initiat Fdn, Subang Jaya, Selangor, Malaysia [ 193 ] Univ Malaya, Med Ctr, Fac Med, Canc Res Inst, Kuala Lumpur, Malaysia [ 194 ] Aichi Canc Ctr Res Inst, Div Mol Med, Nagoya, Aichi, Japan [ 195 ] Aichi Canc Ctr Res Inst, Div Epidemiol & Prevent, Nagoya, Aichi, Japan [ 196 ] Univ Malaya, Med Ctr, Dept Obstet & Gynecol, Kuala Lumpur, Malaysia [ 197 ] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China [ 198 ] Masaryk Mem Canc Inst & Med Fac, Brno, Czech Republic [ 199 ] Med Univ Vienna, Dept Obstet & Gynecol, Vienna, Austria [ 200 ] Med Univ Vienna, Ctr Comprehens Canc, Vienna, Austria [ 201 ] Sheba Med Ctr, Susanne Levy Gertner Oncogenet Unit, Tel Hashomer, Israel [ 202 ] Carmel Hosp, Clalit Natl Israeli Canc Control Ctr, Haifa, Israel [ 203 ] Carmel Hosp, Dept Community Med & Epidemiol, Haifa, Israel [ 204 ] B Rappaport Fac Med, Haifa, Israel [ 205 ] NN Petrov Inst Oncol, St Petersburg, Russia [ 206 ] NorthShore Univ Hlth Syst, Ctr Med Genet, Evanston, IL USA [ 207 ] Univ Chicago, Med Ctr, Ctr Clin Canc Genet & Global Hlth, Chicago, IL 60637 USA [ 208 ] Ohio State Univ, Ctr Comprehens Canc, Dept Internal Med, Div Human Genet, Columbus, OH 43210 USA [ 209 ] Natl Inst Oncol, Dept Mol Genet, Budapest, Hungary [ 210 ] Dartmouth Coll, Geisel Sch Med, Sect Biostat & Epidemiol, Dept Community & Family Med, Hanover, NH 03755 USA [ 211 ] Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27710 USA [ 212 ] Duke Canc Inst, Canc Control & Populat Sci, Durham, NC USA [ 213 ] Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, NL-6525 ED Nijmegen, Netherlands [ 214 ] Radboud Univ Nijmegen, Med Ctr, Radboud Inst Mol Life Sci, Dept Gynaecol, NL-6525 ED Nijmegen, Netherlands [ 215 ] Univ New Mexico, Dept Internal Med, Div Epidemiol & Biostat, Albuquerque, NM 87131 USA [ 216 ] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Portland, OR 97201 USA [ 217 ] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA [ 218 ] Lund Univ, Dept Oncol, Lund, Sweden [ 219 ] Sahlgrens Univ Hosp, Dept Clin Genet, Gothenburg, Sweden [ 220 ] Fred Hutchinson Canc Res Ctr, Program Epidemiol, 1124 Columbia St, Seattle, WA 98104 USA [ 221 ] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA [ 222 ] Univ Lund Hosp, Ctr Oncol, Reg Tumour Registry, S-22185 Lund, Sweden [ 223 ] Univ Sheffield, Sheffield Canc Res Dept Oncol, Sheffield, S Yorkshire, England [ 224 ] Univ Sheffield, Dept Neurosci, Acad Unit Pathol, Sheffield, S Yorkshire, England [ 225 ] Pontificia Univ Javeriana, Inst Human Genet, Bogota, Colombia [ 226 ] Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland [ 227 ] Landspitali Univ Hosp, Reykjavik, Iceland Organization-Enhanced Name(s) Landspitali National University Hospital [ 228 ] Univ Iceland, Sch Med, Reykjavik, Iceland [ 229 ] Maria Sklodowska Curie Mem Canc Ctr, Dept Pathol & Lab Diagnost, Warsaw, Poland [ 230 ] Inst Oncol, Warsaw, Poland [ 231 ] Natl Ctr Sci Res Demokritos, Mol Diagnost Lab, Inst Nucl & Radiol Sci & Technol, Energy & Safety, Athens, Greece [ 232 ] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA
Subjects: 0301 basic medicine, Oncology, Male, Cancer Research, endocrine system diseases, LOCI, Estrogen receptor, FAMILY-HISTORY, Prostate cancer, 0302 clinical medicine, Ovarian Neoplasms/pathology, Prostate, Risk Factors, Brjóstakrabbamein, Odds Ratio, skin and connective tissue diseases, Ovarian Neoplasms, Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17], Prostatic Neoplasms/genetics, Research Support, Non-U.S. Gov't, SINGLE-NUCLEOTIDE POLYMORPHISMS, Middle Aged, BRCA2 Protein/genetics, PANCREATIC-CANCER, 3. Good health, SUSCEPTIBILITY GENE, medicine.anatomical_structure, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], 030220 oncology & carcinogenesis, Codon, Terminator, Female, Risk Factors Substances, Adult, medicine.medical_specialty, Heterozygote, Breast Neoplasms, Blöðruhálskirtilskrabbamein, Breast Neoplasms/genetics, Biology, Polymorphism, Single Nucleotide, Risk Assessment, Article, Ovarian Neoplasms/genetics, 03 medical and health sciences, Breast cancer, SDG 3 - Good Health and Well-being, Research Support, N.I.H., Extramural, Internal medicine, Pancreatic cancer, Krabbameinsrannsóknir, medicine, Journal Article, Humans, Genetic Predisposition to Disease, Neoplasm Invasiveness, Lysine/genetics, Krabbamein, Aged, Gynecology, BRCA2 Protein, Proportional hazards model, Lysine, DNA RECOMBINATION, CONSORTIUM, GERM-LINE MUTATION, Prostatic Neoplasms, Odds ratio, Arfgengi, medicine.disease, ESTROGEN-RECEPTOR, 030104 developmental biology, Logistic Models, PTT12, Eggjastokkar, FANCONI-ANEMIA, Ovarian cancer
Abstract: Contains fulltext : 172007.pdf (Publisher’s version ) (Closed access) BACKGROUND: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. METHODS: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. RESULTS: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10(-) (6)) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10(-3)). These associations were stronger for serous ovarian cancer and for estrogen receptor-negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10(-5) and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10(-5), respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. CONCLUSIONS: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations.
Published: 2016

41. A Nonsynonymous Polymorphism in IRS1 Modifies Risk of Developing Breast and Ovarian Cancers in BRCA1 and Ovarian Cancer in BRCA2 Mutation Carriers

Author: Ding, Y.C., McGuffog, L., Healey, S., Friedman, E., Laitman, Y., Shani-Paluch-Shimon, Kaufman, B., Liljegren, A., Lindblom, A., Olsson, H., Kristoffersson, U., Stenmark-Askmalm, M., Melin, B., Domchek, S.M., Nathanson, K.L., Rebbeck, T.R., Jakubowska, A., Lubinski, J., Jaworska, K., Durda, K., Gronwald, J., Huzarski, T., Cybulski, C., Byrski, T., Osorio, A., Cajal, T.R., Stavropoulou, A.V., Benitez, J., Hamann, U., Rookus, M., Aalfs, C.M., Lange, J.L. de, Meijers-Heijboer, H.E.J., Oosterwijk, J.C., Asperen, C.J. van, Garcia, E.B.G., Hoogerbrugge, N., Jager, A., Luijt, R.B. van der, Easton, D.F., Peock, S., Frost, D., Ellis, S.D., Platte, R., Fineberg, E., Evans, D.G., Lalloo, F., Izatt, L., Eeles, R., Adlard, J., Davidson, R., Eccles, D., Cole, T., Cook, J., Brewer, C., Tischkowitz, M., Godwin, A.K., Pathak, H., Stoppa-Lyonnet, D., Sinilnikova, O.M., Mazoyer, S., Barjhoux, L., Leone, M., Gauthier-Villars, M., Caux-Moncoutier, V., Pauw, A. de, Hardouin, A., Berthet, P., Dreyfus, H., Ferrer, S.F., Collonge-Rame, M.A., Sokolowska, J., Buys, S., Daly, M., Miron, A., Terry, M.B., Chung, W., John, E.M., Southey, M., Goldgar, D., Singer, C.F., Tea, M.K.M., Gschwantler-Kaulich, D., Fink-Retter, A., Hansen, T.V.O., Ejlertsen, B., Johannsson, O.T., Offit, K., Sarrel, K., Gaudet, M.M., Vijai, J., Robson, M., Piedmonte, M.R., Andrews, L., Cohn, D., DeMars, L.R., DiSilvestro, P., Rodriguez, G., Toland, A.E., Montagna, M., Agata, S., Imyanitov, E., Isaacs, C., Janavicius, R., Lazaro, C., Blanco, I., Ramus, S.J., Sucheston, L., Karlan, B.Y., Gross, J., Ganz, P.A., Beattie, M.S., Schmutzler, R.K., Wappenschmidt, B., Meindl, A., Arnold, N., Niederacher, D., Preisler-Adams, S., Gadzicki, D., Varon-Mateeva, R., Deissler, H., Gehrig, A., Sutter, C., Kast, K., Nevanlinna, H., Aittomaki, K., Simard, J., Spurdle, A.B., Beesley, J., Chen, X.Q., Tomlinson, G.E., Weitzel, J., Garber, J.E., Olopade, O.I., Rubinstein, W.S., Tung, N., Blum, J.L., Narod, S.A., Brummel, S., Gillen, D.L., Lindor, N., Fredericksen, Z., Pankratz, V.S., Couch, F.J., Radice, P., Peterlongo, P., Greene, M.H., Loud, J.T., Mai, P.L., Andrulis, I.L., Glendon, G., Ozcelik, H., Gerdes, A.M., Thomassen, M., Jensen, U.B., Skytte, A.B., Caligo, M.A., Lee, A., Chenevix-Trench, G., Antoniou, A.C., Neuhausen, S.L., SWE-BRCA, HEBON, EMBRACE, GEMO Study Collaborators, KConFab Investigators, OCGN, Consortium Investigators Modifiers, Human genetics, CCA - Oncogenesis, Genetica & Celbiologie, RS: GROW - School for Oncology and Reproduction, Human Genetics, Cancer Center Amsterdam, Amsterdam Reproduction & Development (AR&D), Medical Oncology, Clinical Genetics, Damage and Repair in Cancer Development and Cancer Treatment (DARE), and Targeted Gynaecologic Oncology (TARGON)
Subjects: Nonsynonymous substitution, endocrine system diseases, Epidemiology, Genes, BRCA2, Genes, BRCA1, Cohort Studies, 0302 clinical medicine, Genotype, skin and connective tissue diseases, Ovarian Neoplasms, 0303 health sciences, GENETIC-VARIATION, INSULIN, 3. Good health, FAMILY, Oncology, 030220 oncology & carcinogenesis, Cohort, Female, Cohort study, EXPRESSION, AMINO-ACID POLYMORPHISM, endocrine system, PROTEINS, Hereditary cancer and cancer-related syndromes Genetics and epigenetic pathways of disease [ONCOL 1], NEOPLASIA, Breast Neoplasms, Biology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, Breast cancer, SDG 3 - Good Health and Well-being, Translational research [ONCOL 3], GROWTH-FACTOR-I, medicine, Humans, Genetic Predisposition to Disease, IGF, 030304 developmental biology, Hereditary cancer and cancer-related syndromes [ONCOL 1], RECEPTOR, Retrospective cohort study, medicine.disease, IRS1, Mutation, Cancer research, Insulin Receptor Substrate Proteins, Ovarian cancer
Abstract: Background: We previously reported significant associations between genetic variants in insulin receptor substrate 1 (IRS1) and breast cancer risk in women carrying BRCA1 mutations. The objectives of this study were to investigate whether the IRS1 variants modified ovarian cancer risk and were associated with breast cancer risk in a larger cohort of BRCA1 and BRCA2 mutation carriers. Methods:IRS1 rs1801123, rs1330645, and rs1801278 were genotyped in samples from 36 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Data were analyzed by a retrospective cohort approach modeling the associations with breast and ovarian cancer risks simultaneously. Analyses were stratified by BRCA1 and BRCA2 status and mutation class in BRCA1 carriers. Results: Rs1801278 (Gly972Arg) was associated with ovarian cancer risk for both BRCA1 (HR, 1.43; 95% confidence interval (CI), 1.06–1.92; P = 0.019) and BRCA2 mutation carriers (HR, 2.21; 95% CI, 1.39–3.52, P = 0.0008). For BRCA1 mutation carriers, the breast cancer risk was higher in carriers with class II mutations than class I mutations (class II HR, 1.86; 95% CI, 1.28–2.70; class I HR, 0.86; 95%CI, 0.69–1.09; Pdifference, 0.0006). Rs13306465 was associated with ovarian cancer risk in BRCA1 class II mutation carriers (HR, 2.42; P = 0.03). Conclusion: The IRS1 Gly972Arg single-nucleotide polymorphism, which affects insulin-like growth factor and insulin signaling, modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers and breast cancer risk in BRCA1 class II mutation carriers. Impact: These findings may prove useful for risk prediction for breast and ovarian cancers in BRCA1 and BRCA2 mutation carriers. Cancer Epidemiol Biomarkers Prev; 21(8); 1362–70. ©2012 AACR.
Published: 2012

42. Assessing Associations between the AURKA-HMMR-TPX2-TUBG1 Functional Module and Breast Cancer Risk in BRCA1/2 Mutation Carriers

Author: Blanco, I., Kuchenbaecker, K., Cuadras, D., Wang, X.S., Barrowdale, D., Garibay, G.R., Librado, P., Sanchez-Gracia, A., Rozas, J., Bonifaci, N., McGuffog, L., Pankratz, V.S., Islam, A., Mateo, F., Berenguer, A., Petit, A., Catala, I., Brunet, J., Feliubadalo, L., Tornero, E., Benitez, J., Osorio, A., Cajal, T.R.Y., Nevanlinna, H., Aittomaki, K., Arun, B.K., Toland, A.E., Karlan, B.Y., Walsh, C., Lester, J., Greene, M.H., Mai, P.L., Nussbaum, R.L., Andrulis, I.L., Domchek, S.M., Nathanson, K.L., Rebbeck, T.R., Barkardottir, R.B., Jakubowska, A., Lubinski, J., Durda, K., Jaworska-Bieniek, K., Claes, K., Maerken, T. van, Diez, O., Hansen, T.V., Jonson, L., Gerdes, A.M., Ejlertsen, B., Hoya, M. de la, Caldees, T., Dunning, A.M., Oliver, C., Fineberg, E., Cook, M., Peock, S., McCann, E., Murray, A., Jacobs, C., Pichert, G., Lalloo, F., Chu, C., Dorkins, H., Paterson, J., Ong, K.R., Teixeira, M.R., Teixeira, Hogervorst, F.B.L., Hout, A.H. van der, Seynaeve, C., Luijt, R.B. van der, Ligtenberg, M.J.L., Devilee, P., Wijnen, J.T., Rookus, M.A., Meijers-Heijboer, H.E.J., Blok, M.J., Ouweland, A.M.W. van den, Aalfs, C.M., Rodriguez, G.C., Phillips, K.A.A., Piedmonte, M., Nerenstone, S.R., Bae-Jump, V.L., O'Malley, D.M., Ratner, E.S., Schmutzler, R.K., Wappenschmidt, B., Rhiem, K., Engel, C., Meindl, A., Ditsch, N., Arnold, N., Plendl, H.J., Niederacher, D., Sutter, C., Wang-Gohrke, S., Steinemann, D., Preisler-Adams, S., Kast, K., Varon-Mateeva, R., Gehrig, A., Bojesen, A., Pedersen, I.S., Sunde, L., Jensen, U.B., Thomassen, M., Kruse, T.A., Foretova, L., Peterlongo, P., Bernard, L., Peissel, B., Scuvera, G., Manoukian, S., Radice, P., Ottini, L., Montagna, M., Agata, S., Maugard, C., Simard, J., Soucy, P., Berger, A., Fink-Retter, A., Singer, C.F., Rappaport, C., Geschwantler-Kaulich, D., Tea, M.K., Pfeiler, G., John, E.M., Miron, A., Neuhausen, S.L., Terry, M.B., Chung, W.K., Daly, M.B., Goldgar, D.E., Janavicius, R., Dorfling, C.M., Rensburg, E.J. van, Fostira, F., Konstantopoulou, I., Garber, J., Godwin, A.K., Olah, E., Narod, S.A., Rennert, G., Paluch, S.S., Laitman, Y., Friedman, E., Liljegren, A., Rantala, J., Stenmark-Askmalm, M., Loman, N., Imyanitov, E.N., Hamann, U., Spurdle, A.B., Healey, S., Weitzel, J.N., Herzog, J., Margileth, D., Gorrini, C., Esteller, M., Gomez, A., Sayols, S., Vidal, E., Heyn, H., Stoppa-Lyonnet, Leone, M., Barjhoux, L., Fassy-Colcombet, M., Pauw, A. de, Lasset, C., Ferrer, S.F., Castera, L., Berthet, P., Cornelis, F., Bignon, Y.J., Damiola, F., Mazoyer, S., Sinilnikova, O.M., Maxwell, C.A., Vijai, J., Robson, M., Kauff, N., Corines, M.J., Villano, D., Cunningham, J., Lee, A., Lindor, N., Lazaro, C., Easton, D.F., Offit, K., Chenevix-Trench, G., Couch, F.J., Antoniou, A.C., Pujana, M.A., BCFR, SWE-BRCA, KConFab Investigators, GEMO, Human genetics, CCA - Oncogenesis, Medical Oncology, Clinical Genetics, Suzuki, Hiromu, MUMC+: DA KG Lab Centraal Lab (9), RS: GROW - Oncology, RS: GROW - R4 - Reproductive and Perinatal Medicine, CCA -Cancer Center Amsterdam, ARD - Amsterdam Reproduction and Development, Human Genetics, Department of Obstetrics and Gynecology, Clinicum, Medicum, Haartman Institute (-2014), and Department of Medical and Clinical Genetics
Subjects: single nucleotide, Oncology, Carcinogenesis, TUBG1, Genes, BRCA2, Genes, BRCA1, Càncer d'ovari, MODIFIERS, Genome-wide association study, Cell Cycle Proteins, Breast cancer, mammary glands, Aetiology, genes, skin and connective tissue diseases, Cancer, Extracellular Matrix Proteins, Hazard ratio, CHIP-SEQ, 3. Good health, ddc, Hyaluronan Receptors, Medicine, Teixeira, Human, medicine.medical_specialty, Evolution, Science, Non-P.H.S, Single-nucleotide polymorphism, Evolution, Molecular, SDG 3 - Good Health and Well-being, Ovarian cancer, Genetics, biochemistry, Humans, human, CELL, Polymorphism, GENOME-WIDE ASSOCIATION, medicine (all), Retrospective Studies, Cancer och onkologi, Prevention, Mutació (Biologia), Biology and Life Sciences, Molecular, SWE-BRCA, BRCA1, medicine.disease, BRCA2, POLYMORPHISM, Genes, Genetic Loci, Cancer and Oncology, Mutation, U.S. Gov't, Bioinformatics, medicine.disease_cause, 3123 Gynaecology and paediatrics, Tubulin, Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14], ELEMENTS, 2.1 Biological and endogenous factors, CD44, Non-U.S. Gov't, Aurora Kinase A, Likelihood Functions, Multidisciplinary, Research Support, Non-U.S. Gov't, agricultural and biological sciences (all), genetics and molecular biology (all), BCFR, Nuclear Proteins, Single Nucleotide, Mammary Glands, SURVIVAL, kConFab Investigators, Female, Microtubule-Associated Proteins, Research Article, Antigens, CD44, aurora kinase A, breast neoplasms, carcinogenesis, cell cycle proteins, estrogen receptor alpha, evolution, molecular, extracellular matrix proteins, female, genetic loci, genetic predisposition to disease, humans, likelihood functions, mammary glands, human, microtubule-associated proteins, nuclear proteins, polymorphism, retrospective studies, tubulin, genes, BRCA1, genes, BRCA2, mutation, biochemistry, genetics and molecular biology (all), SUSCEPTIBILITY LOCI, General Science & Technology, 3122 Cancers, Breast Neoplasms, Biology, Research Support, Polymorphism, Single Nucleotide, N.I.H, GENETIC INTERACTION NETWORKS, Càncer de mama, EXPRESSION SIGNATURE, Amino acid sequence, Research Support, N.I.H., Extramural, Internal medicine, Seqüència d'aminoàcids, evolution, Genetic variation, Journal Article, medicine, Genetic Predisposition to Disease, ddc:610, molecular, Antigens, Mammary Glands, Human, ddc:611, Intramural, Estrogen Receptor alpha, Extramural, Mutation (Biology), Research Support, N.I.H., Intramural, 3111 Biomedicine, GEMO, Research Support, U.S. Gov't, Non-P.H.S
Abstract: While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR) = 1.10, 95% confidence interval (CI) 1.04 - 1.15, p = 1.9 x 10(-4) (false discovery rate (FDR)-adjusted p = 0.043). Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95% CI 1.03 - 1.16, p = 0.005 (FDR-adjusted p = 0.045). Assessment of pairwise interactions provided suggestions (FDR-adjusted p(interaction) values greater than 0.05) for deviations from the multiplicative model for rs299290 and CSTF1 rs6064391, and rs299290 and TUBG1 rs11649877 in both BRCA1 and BRCA2 mutation carriers. Following these suggestions, the expression of HMMR and AURKA or TUBG1 in sporadic breast tumors was found to potentially interact, influencing patients survival. Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers. Funding Agencies|National Cancer Institute [UM1 CA164920]; Lithuania (BFBOCC-LT): Research Council of Lithuania grant [LIG-07/2012]; Hereditary Cancer Association (Paveldimo vezio asociacija); LSC grant [10.0010.08]; ESF [2009/0220/1DP/1.1.1.2.0/09/APIA/VIAA/016]; Liepajas municipal council; Cancer Association of South Africa (CANSA); Morris and Horowitz Familes Endowed Professorship; NEYE Foundation; Spanish Association against Cancer [AECC08, RTICC 06/0020/1060, FISPI08/1120]; Mutua Madrilena Foundation (FMMA); COH-CCGCRN: City of Hope Clinical Cancer Genetics Community Network from the National Cancer Institute and the Office of the Director, National Institutes of Health; Hereditary Cancer Research Registry from the National Cancer Institute and the Office of the Director, National Institutes of Health [RC4CA153828]; Fondazione IRCCS Istituto Nazionale Tumori; Cancer Research-United Kingdom grant [C12292/A11174, C1287/ A10118]; NHMRC Program Grant; DKFZ; European Union (European Social Fund-ESF); Greek national funds through the Operational Program "Education and Lifelong Learning" of the National Strategic Reference Framework (NSRF)-Research Funding Program of the General Secretariat for Research and Technology: ARISTEIA; European Social Fund; Cancer Research United Kingdom Grants [C1287/A10118, C1287/A11990]; National Institute of Health Research (NIHR) grant; NIHR grant; Royal Marsden NHS Foundation Trust; Cancer Research United Kingdom Grant [C5047/A8385]; University of Kansas Cancer Center [P30 CA168524]; Kansas Bioscience Authority Eminent Scholar Program; Chancellors Distinguished Chair in Biomedical Sciences Professorship; AKG [5U01CA113916, R01CA140323]; German Cancer Aid [109076]; Center for Molecular Medicine Cologne (CMMC); Ligue National Contre le Cancer; Association "Le cancer du sein, parlonsen!" Award; Canadian Institutes of Health Research; Fund for Scientific Research Flanders (FWO); National Cancer Institute grant [CA 27469]; GOG Statistical and Data Center [CA 37517]; GOGs Cancer Prevention and Control Committee [CA 101165]; Intramural Research Program, NCI; ISCIII (Spain) [RD12/00369/0006, 12/00539]; European Regional Development FEDER funds; Helsinki University Central Hospital Research Fund; Academy of Finland [132473]; Finnish Cancer Society; Sigrid Juselius Foundation; Dutch Cancer Society grant [NKI1998-1854, NKI2004-3088, NKI2007-3756]; Netherlands Organization of Scientific Research [NWO 91109024]; Pink Ribbon grant [110005]; BBMRI grant [NWO 184.021.007/CP46]; Hungarian Research Grant [KTIA-OTKA CK-80745]; Norwegian EEA Financial Mechanism [HU0115/NA/2008-3/OP-9]; Spanish Ministry of Health ISCIII FIS [PI10/01422, PI12/01528, PI13/00285]; RTICC [RD12/0036/0008]; Ramon Areces (XV) Foundation; Eugenio Rodriguez Pascual Foundation; Roses Contra el Cancer Foundation; Spanish Association Against Cancer (AECC); AGAUR Generalitat de Catalunya [2009-SGR290, 2009-SGR293]; Polish Foundation of Science; Icelandic Association "Walking for Breast Cancer Research"; Nordic Cancer Union; Landspitali University Hospital Research Fund; Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program; Canadian Breast Cancer Research Alliance-grant [019511]; Ministry of Economic Development, Innovation and Export Trade-grant [PSR-SIIRI-701]; Ministero dellIstruzione, dellUniversita e della Ricerca and Ministero della Salute; Liga Portuguesa Contra o Cancro; National Breast Cancer Foundation; National Health and Medical Research Council (NHMRC); Queensland Cancer Fund; Cancer Council of New South Wales; Cancer Council of Victoria; Cancer Foundation of Western Australia; Cancer Councils of Tasmania; National Institutes of Health grant [CA128978]; NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201]; United States Department of Defence Ovarian Cancer Idea award [W81XWH-10-1-0341]; Breast Cancer Research Foundation; Jewish General Hospital Weekend; Quebec Ministry of Economic Development, Innovation and Export Trade; Cancer Councils of South Australia; European Regional Development Fund; State Budget of the Czech Republic (RECAMO) [CZ.1.05/2.1.00/03.0101]; MH CZ-DRO (MMCI) [00209805]; Niehaus Family Genetics Research Fund; STARR Cancer Consortium Grant; NAROD [1R01 CA149429-01]; NCI Intramural Research Program, National Institutes of Health [NO2-CP-11019-50, N02-CP-65504]; Westat, Inc, Rockville, Maryland; Clalit Health Services in Israel; Israel Cancer Association; Breast Cancer Research Foundation (BCRF), New York; Russian Federation for Basic Research [11-04-00227, 12-04-00928, 12-04-01490]; Federal Agency for Science and Innovations, Russia [02.740.11.0780]; Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program and grant from the National Cancer Institute [UM1 CA164920]; Breast Cancer Family Registry (BCFR); United States Government or the BCFR; Ohio State University Comprehensive Cancer Center; Isreal cancer association; Israeli Inherited breast cancer consortium; Swedish Cancer Society; Ralph and Marion Falk Medical Research Trust; Entertainment Industry Fund National Womens Cancer Research Alliance; National Institutes of Health (NIH) [R01-CA102776, R01-CA083855]; Rooney Family Foundation; Susan G. Komen Foundation for the cure, Basser Research Center; American Cancer Society Early Detection Professorship [SIOP-06-258-01-COUN]; SAF2010-20493; [PBZ_KBN_122/P05/2004]
Published: 2015

43. Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus

Author: Zeng, C. (Chenjie), Guo, X. (Xingyi), Long, J. (Jirong), Kuchenbaecker, K.B. (Karoline), Droit, A. (Arnaud), Michailidou, K. (Kyriaki), Ghoussaini, M. (Maya), Kar, S. (Siddhartha), Freeman, A. (Adam), Hopper, J.L. (John), Milne, R.L. (Roger), Bolla, M.K. (Manjeet K.), Wang, Q. (Qin), Dennis, J. (Joe), Agata, S. (Simona), Ahmed, S. (Shahana), Aittomäki, K. (Kristiina), Andrulis, I.L. (Irene), Anton-Culver, H. (Hoda), Antonenkova, N.N. (Natalia N.), Arason, A. (Adalgeir), Arndt, V. (Volker), Arun, B.K. (Banu), Arver, B. (Brita Wasteson), Bacot, F. (Francois), Barrowdale, D. (Daniel), Baynes, C. (Caroline), Beeghly-Fadiel, A. (Alicia), Benítez, J. (Javier), Bermisheva, M. (Marina), Blomqvist, C. (Carl), Blot, W.J. (William), Bogdanova, N.V. (Natalia), Bojesen, S.E. (Stig), Bonnani, B. (Bernardo), Borresen-Dale, A.-L. (Anne-Lise), Brand, J.S. (Judith S.), Brauch, H. (Hiltrud), Brennan, P. (Paul), Brenner, H. (Hermann), Broeks, A. (Annegien), Brüning, T. (Thomas), Burwinkel, B. (Barbara), Buys, S.S. (Saundra), Cai, Q. (Qiuyin), Caldes, T. (Trinidad), Campbell, I. (Ian), Carpenter, T.A. (Adrian), Chang-Claude, J. (Jenny), Choi, J.-Y. (Ji-Yeob), Claes, K.B.M. (Kathleen B.M.), Clarke, C. (Christine), Cox, A. (Angela), Cross, S.S. (Simon), Czene, K. (Kamila), Daly, M.B. (Mary B.), Hoya, M. (Miguel) de La, De Leeneer, K. (Kim), Devilee, P. (Peter), Díez, O. (Orland), Domchek, S.M. (Susan), Doody, M. (Michele), Dorfling, C.M. (Cecilia), Dörk, T. (Thilo), Santos Silva, I. (Isabel) dos, Dumont, M. (Martine), Dwek, M. (Miriam), Dworniczak, B. (Bernd), Egan, K.M. (Kathleen), Eilber, U. (Ursula), Einbeigi, Z. (Zakaria), Ejlertsen, B. (Bent), Ellis, S.D. (Steve), Frost, D. (Debra), Lalloo, F. (Fiona), Fasching, P.A. (Peter), Figueroa, J.D. (Jonine), Flyger, H. (Henrik), Friedlander, M. (Michael), Friedman, E. (Eitan), Gambino, G. (Gaetana), Gao, Y.-T. (Yu-Tang), Garber, J. (Judy), García-Closas, M. (Montserrat), Gehrig, P.A. (Paola A.), Damiola, F. (Francesca), Lesueur, F. (Fabienne), Mazoyer, S. (Sylvie), Stoppa-Lyonnet, D. (Dominique), Giles, G.G. (Graham G.), Godwin, A.K. (Andrew K.), Goldgar, D. (David), González-Neira, A. (Anna), Greene, M.H. (Mark H.), Guénel, P. (Pascal), Haeberle, L. (Lothar), Haiman, C.A. (Christopher A.), Hallberg, E. (Emily), Hamann, U. (Ute), Hansen, T.V.O. (Thomas), Hart, S. (Stewart), Hartikainen, J.M. (J.), Hartman, J.M. (Joost), Hassan, N. (Norhashimah), Healey, S. (Sue), Hogervorst, F.B.L. (Frans), Verhoef, S., Hendricks, C.B. (Carolyn B.), Hillemanns, P. (Peter), Hollestelle, A. (Antoinette), Hulick, P.J. (Peter), Hunter, D. (David), Imyanitov, E.N. (Evgeny), Isaacs, C. (Claudine), Ito, H. (Hidemi), Jakubowska, A. (Anna), Janavicius, R. (Ramunas), Jaworska-Bieniek, K. (Katarzyna), Jensen, U.B., John, E.M. (Esther), Joly Beauparlant, C. (Charles), Jones, M. (Michael), Kabisch, M. (Maria), Kang, D. (Daehee), Karlan, B.Y. (Beth Y.), Kauppila, S. (Saila), Kerin, M. (Michael), Khan, S. (Sofia), Khusnutdinova, E.K. (Elza), Knight, J.A. (Julia), Konstantopoulou, I. (I.), Kraft, P. (Peter), Kwong, A. (Ava), Laitman, Y. (Yael), Lambrechts, D. (Diether), Lázaro, C. (Conxi), Le Marchand, L. (Loic), Lee, C.N. (Chuen), Lee, M.H. (Min Hyuk), Lester, K.J. (Kathryn), Li, J. (Jingmei), Liljegren, A. (Annelie), Lindblom, A. (Annika), Lophatananon, A. (Artitaya), Lubinski, J. (Jan), Mai, P.L. (Phuong), Mannermaa, A. (Arto), Manoukian, S. (Siranoush), Margolin, S. (Sara), Marme, F. (Frederik), Matsuo, K. (Keitaro), McGuffog, L. (Lesley), Meindl, A. (Alfons), Menegaux, F. (Florence), Montagna, M. (Marco), Muir, K.R. (K.), Mulligan, A.-M. (Anna-Marie), Nathanson, K.L. (Katherine), Neuhausen, S.L. (Susan), Nevanlinna, H. (Heli), Newcomb, P. (Polly), Nord, S. (Silje), Nussbaum, R.L. (Robert L.), Offit, K. (Kenneth), Olah, E., Olopade, O.I. (Olufunmilayo I.), Olswold, C. (Curtis), Osorio, A. (Ana), Papi, L. (Laura), Park-Simon, T.-W., Paulsson-Karlsson, Y. (Ylva), Peeters, S.T.H. (Stephanie), Peissel, B. (Bernard), Peterlongo, P. (Paolo), Peto, J. (Julian), Pfeiler, G. (Georg), Phelan, C. (Catherine), Presneau, N. (Nadege), Radice, P. (Paolo), Rahman, N. (Nazneen), Ramus, S.J. (Susan), Rashid, M.U. (Muhammad), Rennert, G. (Gad), Rhiem, K. (Kerstin), Rudolph, A. (Anja), Salani, R. (Ritu), Sangrajrang, S. (Suleeporn), Sawyer, E.J. (Elinor), Schmidt, M.K. (Marjanka), Schmutzler, R.K. (Rita), Schoemaker, M. (Minouk), Schürmann, P. (Peter), Seynaeve, C.M. (Caroline), Shen, C.-Y. (Chen-Yang), Shrubsole, M. (Martha), Shu, X.-O. (Xiao-Ou), Sigurdson, A.J. (Alice), Singer, C.F. (Christian), Slager, S. (Susan), Soucy, P. (Penny), Southey, M.C. (Melissa), Steinemann, D. (Doris), Swerdlow, A.J. (Anthony ), Szabo, C. (Csilla), Tchatchou, S. (Sandrine), Teixeira, P.J., Teo, S.-H. (Soo-Hwang), Terry, M.B. (Mary Beth), Tessier, D.C. (Daniel C.), Teulé, A. (A.), Thomassen, M. (Mads), Tihomirova, L. (Laima), Tischkowitz, M. (Marc), Toland, A.E. (Amanda), Tung, N. (Nadine), Turnbull, C. (Clare), Ouweland, A.M.W. (Ans) van den, Rensburg, E.J. (Elizabeth) van, ven den Berg, D. (David), Vijai, J. (Joseph), Wang-Gohrke, S. (Shan), Weitzel, J.N. (Jeffrey), Whittemore, A.S. (Alice), Winqvist, R. (Robert), Wong, T.Y. (Tien Y.), Wu, A.H. (Anna), Yannoukakos, D. (Drakoulis), Yu, J-C. (Jyh-Cherng), Pharoah, P.D.P. (Paul), Hall, P. (Per), Chenevix-Trench, G. (Georgia), Dunning, A.M. (Alison), Simard, J. (Jacques), Couch, F.J. (Fergus), Antoniou, A.C. (Antonis), Easton, D.F. (Douglas F.), Zheng, W. (Wei), Zeng, C. (Chenjie), Guo, X. (Xingyi), Long, J. (Jirong), Kuchenbaecker, K.B. (Karoline), Droit, A. (Arnaud), Michailidou, K. (Kyriaki), Ghoussaini, M. (Maya), Kar, S. (Siddhartha), Freeman, A. (Adam), Hopper, J.L. (John), Milne, R.L. (Roger), Bolla, M.K. (Manjeet K.), Wang, Q. (Qin), Dennis, J. (Joe), Agata, S. (Simona), Ahmed, S. (Shahana), Aittomäki, K. (Kristiina), Andrulis, I.L. (Irene), Anton-Culver, H. (Hoda), Antonenkova, N.N. (Natalia N.), Arason, A. (Adalgeir), Arndt, V. (Volker), Arun, B.K. (Banu), Arver, B. (Brita Wasteson), Bacot, F. (Francois), Barrowdale, D. (Daniel), Baynes, C. (Caroline), Beeghly-Fadiel, A. (Alicia), Benítez, J. (Javier), Bermisheva, M. (Marina), Blomqvist, C. (Carl), Blot, W.J. (William), Bogdanova, N.V. (Natalia), Bojesen, S.E. (Stig), Bonnani, B. (Bernardo), Borresen-Dale, A.-L. (Anne-Lise), Brand, J.S. (Judith S.), Brauch, H. (Hiltrud), Brennan, P. (Paul), Brenner, H. (Hermann), Broeks, A. (Annegien), Brüning, T. (Thomas), Burwinkel, B. (Barbara), Buys, S.S. (Saundra), Cai, Q. (Qiuyin), Caldes, T. (Trinidad), Campbell, I. (Ian), Carpenter, T.A. (Adrian), Chang-Claude, J. (Jenny), Choi, J.-Y. (Ji-Yeob), Claes, K.B.M. (Kathleen B.M.), Clarke, C. (Christine), Cox, A. (Angela), Cross, S.S. (Simon), Czene, K. (Kamila), Daly, M.B. (Mary B.), Hoya, M. (Miguel) de La, De Leeneer, K. (Kim), Devilee, P. (Peter), Díez, O. (Orland), Domchek, S.M. (Susan), Doody, M. (Michele), Dorfling, C.M. (Cecilia), Dörk, T. (Thilo), Santos Silva, I. (Isabel) dos, Dumont, M. (Martine), Dwek, M. (Miriam), Dworniczak, B. (Bernd), Egan, K.M. (Kathleen), Eilber, U. (Ursula), Einbeigi, Z. (Zakaria), Ejlertsen, B. (Bent), Ellis, S.D. (Steve), Frost, D. (Debra), Lalloo, F. (Fiona), Fasching, P.A. (Peter), Figueroa, J.D. (Jonine), Flyger, H. (Henrik), Friedlander, M. (Michael), Friedman, E. (Eitan), Gambino, G. (Gaetana), Gao, Y.-T. (Yu-Tang), Garber, J. (Judy), García-Closas, M. (Montserrat), Gehrig, P.A. (Paola A.), Damiola, F. (Francesca), Lesueur, F. (Fabienne), Mazoyer, S. (Sylvie), Stoppa-Lyonnet, D. (Dominique), Giles, G.G. (Graham G.), Godwin, A.K. (Andrew K.), Goldgar, D. (David), González-Neira, A. (Anna), Greene, M.H. (Mark H.), Guénel, P. (Pascal), Haeberle, L. (Lothar), Haiman, C.A. (Christopher A.), Hallberg, E. (Emily), Hamann, U. (Ute), Hansen, T.V.O. (Thomas), Hart, S. (Stewart), Hartikainen, J.M. (J.), Hartman, J.M. (Joost), Hassan, N. (Norhashimah), Healey, S. (Sue), Hogervorst, F.B.L. (Frans), Verhoef, S., Hendricks, C.B. (Carolyn B.), Hillemanns, P. (Peter), Hollestelle, A. (Antoinette), Hulick, P.J. (Peter), Hunter, D. (David), Imyanitov, E.N. (Evgeny), Isaacs, C. (Claudine), Ito, H. (Hidemi), Jakubowska, A. (Anna), Janavicius, R. (Ramunas), Jaworska-Bieniek, K. (Katarzyna), Jensen, U.B., John, E.M. (Esther), Joly Beauparlant, C. (Charles), Jones, M. (Michael), Kabisch, M. (Maria), Kang, D. (Daehee), Karlan, B.Y. (Beth Y.), Kauppila, S. (Saila), Kerin, M. (Michael), Khan, S. (Sofia), Khusnutdinova, E.K. (Elza), Knight, J.A. (Julia), Konstantopoulou, I. (I.), Kraft, P. (Peter), Kwong, A. (Ava), Laitman, Y. (Yael), Lambrechts, D. (Diether), Lázaro, C. (Conxi), Le Marchand, L. (Loic), Lee, C.N. (Chuen), Lee, M.H. (Min Hyuk), Lester, K.J. (Kathryn), Li, J. (Jingmei), Liljegren, A. (Annelie), Lindblom, A. (Annika), Lophatananon, A. (Artitaya), Lubinski, J. (Jan), Mai, P.L. (Phuong), Mannermaa, A. (Arto), Manoukian, S. (Siranoush), Margolin, S. (Sara), Marme, F. (Frederik), Matsuo, K. (Keitaro), McGuffog, L. (Lesley), Meindl, A. (Alfons), Menegaux, F. (Florence), Montagna, M. (Marco), Muir, K.R. (K.), Mulligan, A.-M. (Anna-Marie), Nathanson, K.L. (Katherine), Neuhausen, S.L. (Susan), Nevanlinna, H. (Heli), Newcomb, P. (Polly), Nord, S. (Silje), Nussbaum, R.L. (Robert L.), Offit, K. (Kenneth), Olah, E., Olopade, O.I. (Olufunmilayo I.), Olswold, C. (Curtis), Osorio, A. (Ana), Papi, L. (Laura), Park-Simon, T.-W., Paulsson-Karlsson, Y. (Ylva), Peeters, S.T.H. (Stephanie), Peissel, B. (Bernard), Peterlongo, P. (Paolo), Peto, J. (Julian), Pfeiler, G. (Georg), Phelan, C. (Catherine), Presneau, N. (Nadege), Radice, P. (Paolo), Rahman, N. (Nazneen), Ramus, S.J. (Susan), Rashid, M.U. (Muhammad), Rennert, G. (Gad), Rhiem, K. (Kerstin), Rudolph, A. (Anja), Salani, R. (Ritu), Sangrajrang, S. (Suleeporn), Sawyer, E.J. (Elinor), Schmidt, M.K. (Marjanka), Schmutzler, R.K. (Rita), Schoemaker, M. (Minouk), Schürmann, P. (Peter), Seynaeve, C.M. (Caroline), Shen, C.-Y. (Chen-Yang), Shrubsole, M. (Martha), Shu, X.-O. (Xiao-Ou), Sigurdson, A.J. (Alice), Singer, C.F. (Christian), Slager, S. (Susan), Soucy, P. (Penny), Southey, M.C. (Melissa), Steinemann, D. (Doris), Swerdlow, A.J. (Anthony ), Szabo, C. (Csilla), Tchatchou, S. (Sandrine), Teixeira, P.J., Teo, S.-H. (Soo-Hwang), Terry, M.B. (Mary Beth), Tessier, D.C. (Daniel C.), Teulé, A. (A.), Thomassen, M. (Mads), Tihomirova, L. (Laima), Tischkowitz, M. (Marc), Toland, A.E. (Amanda), Tung, N. (Nadine), Turnbull, C. (Clare), Ouweland, A.M.W. (Ans) van den, Rensburg, E.J. (Elizabeth) van, ven den Berg, D. (David), Vijai, J. (Joseph), Wang-Gohrke, S. (Shan), Weitzel, J.N. (Jeffrey), Whittemore, A.S. (Alice), Winqvist, R. (Robert), Wong, T.Y. (Tien Y.), Wu, A.H. (Anna), Yannoukakos, D. (Drakoulis), Yu, J-C. (Jyh-Cherng), Pharoah, P.D.P. (Paul), Hall, P. (Per), Chenevix-Trench, G. (Georgia), Dunning, A.M. (Alison), Simard, J. (Jacques), Couch, F.J. (Fergus), Antoniou, A.C. (Antonis), Easton, D.F. (Douglas F.), and Zheng, W. (Wei)
Abstract: Background: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. Method: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/ ), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. Results: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 × 10-9), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 × 10-5), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 × 10-4) identified in the general populations, and rs113824616 (P = 7 × 10-5) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05. Conclusion: This study id
Published: 2016
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44. Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

Author: Lawrenson, K. (Kate), Kar, S. (Siddhartha), McCue, K. (Karen), Kuchenbaeker, K. (Karoline), Michailidou, K. (Kyriaki), Tyrer, J.P. (Jonathan), Beesley, J. (Jonathan), Ramus, S.J. (Susan), Li, Q. (Qiyuan), Delgado, M.K. (Melissa K.), Lee, J.M. (Janet M.), Aittomäki, K. (Kristiina), Andrulis, I.L. (Irene), Anton-Culver, H. (Hoda), Arndt, V. (Volker), Arun, B.K. (Banu), Arver, B. (Brita Wasteson), Bandera, E.V. (Elisa), Barile, M. (Monica), Barkardottir, R.B. (Rosa B.), Barrowdale, D. (Daniel), Beckmann, M.W. (Matthias), Benítez, J. (Javier), Berchuck, A. (Andrew), Bisogna, M. (Maria), Bjorge, L. (Line), Blomqvist, C. (Carl), Blot, W.J. (William), Bogdanova, N.V. (Natalia), Bojesen, A. (Anders), Bojesen, S.E. (Stig), Bolla, M.K. (Manjeet K.), Bonnani, B. (Bernardo), Borresen-Dale, A.-L. (Anne-Lise), Brauch, H. (Hiltrud), Brennan, P. (Paul), Brenner, H. (Hermann), Bruinsma, F. (Fiona), Brunet, J. (Joan), Buhari, S.A.B.S. (Shaik Ahmad Bin Syed), Burwinkel, B. (Barbara), Butzow, R. (Ralf), Buys, S.S. (Saundra), Cai, Q. (Qiuyin), Caldes, T. (Trinidad), Campbell, I. (Ian), Canniotto, R. (Rikki), Chang-Claude, J. (Jenny), Chiquette, J. (Jocelyne), Choi, J.-Y. (Ji-Yeob), Claes, K.B.M. (Kathleen B.M.), Cook, L.S. (Linda S.), Cox, A. (Angela), Cramer, D.W. (Daniel), Cross, S.S. (Simon), Cybulski, C. (Cezary), Czene, K. (Kamila), Daly, M.B. (Mary B.), Damiola, F. (Francesca), Dansonka-Mieszkowska, A. (Agnieszka), Darabi, H. (Hatef), Dennis, J. (Joe), Devilee, P. (Peter), Díez, O. (Orland), Doherty, J.A. (Jennifer A.), Domchek, S.M. (Susan), Dorfling, C.M. (Cecilia), Dörk, T. (Thilo), Dumont, M. (Martine), Ehrencrona, H. (Hans), Ejlertsen, B. (Bent), Ellis, S.D. (Steve), Engel, C. (Christoph), Lee, E. (Eunjung), Evans, D.G. (D. Gareth), Fasching, P.A. (Peter), Feliubadaló, L. (L.), Figueroa, J.D. (Jonine), Flesch-Janys, D. (Dieter), Fletcher, O. (Olivia), Flyger, H. (Henrik), Foretova, L. (Lenka), Fostira, F. (Florentia), Foulkes, W.D. (William), Fridley, B.L. (Brooke), Friedman, E. (Eitan), Frost, D. (Debra), Gambino, G. (Gaetana), Ganz, P.A. (Patricia A.), Garber, J. (Judy), García-Closas, M. (Montserrat), Gentry-Maharaj, A. (Aleksandra), Ghoussaini, M. (Maya), Giles, G.G. (Graham), Glasspool, R. (Rosalind), Godwin, A.K. (Andrew K.), Goldberg, M.S. (Mark), Goldgar, D. (David), González-Neira, A. (Anna), Goode, E.L. (Ellen), Goodman, M.T. (Marc), Greene, M.H. (Mark H.), Gronwald, J. (Jacek), Guénel, P. (Pascal), Haiman, C.A. (Christopher A.), Hall, P. (Per), Hallberg, E. (Emily), Hamann, U. (Ute), Hansen, T.V.O. (Thomas), harrington, P. (Patricia), Hartman, J.M. (Joost), Hassan, N. (Norhashimah), Healey, S. (Sue), Heitz, P.U., Herzog, J. (Josef), Høgdall, E. (Estrid), Høgdall, C.K. (Claus), Hogervorst, F.B.L. (Frans), Hollestelle, A. (Antoinette), Hopper, J.L. (John), Hulick, P.J. (Peter), Huzarski, T. (Tomasz), Imyanitov, E.N. (Evgeny), Isaacs, C. (Claudine), Ito, H. (Hidemi), Jakubowska, A. (Anna), Janavicius, R. (Ramunas), Jensen, A. (Allan), John, E.M. (Esther), Johnson, N. (Nichola), Kabisch, M. (Maria), Kang, D. (Daehee), Kapuscinski, M.K. (Miroslav K.), Karlan, B.Y. (Beth Y.), Khan, S. (Sofia), Kiemeney, L.A.L.M. (Bart), Kjaer, M. (Michael), Knight, J.A. (Julia), Konstantopoulou, I. (I.), Kosma, V-M. (Veli-Matti), Kristensen, V. (Vessela), Kupryjanczyk, J. (Jolanta), Kwong, A. (Ava), Hoya, M. (Miguel) de La, Laitman, Y. (Yael), Lambrechts, D. (Diether), Le, N.D. (Nhu D.), De Leeneer, K. (Kim), Lester, K.J. (Kathryn), Levine, D.A. (Douglas), Li, J. (Jingmei), Lindblom, A. (Annika), Long, J. (Jirong), Lophatananon, A. (Artitaya), Loud, J.T. (Jennifer), Lu, K.H. (Karen), Lubinski, J. (Jan), Mannermaa, A. (Arto), Manoukian, S. (Siranoush), Le Marchand, L. (Loic), Margolin, S. (Sara), Marme, F. (Frederick), Massuger, L.F. (Leon), Matsuo, K. (Keitaro), Mazoyer, S. (Sylvie), McGuffog, L. (Lesley), McLean, C.A. (Catriona Ann), McNeish, I. (Iain), Meindl, A. (Alfons), Menon, U. (Usha), Mensenkamp, A.R. (Arjen R.), Milne, R.L. (Roger), Montagna, M. (Marco), Moysich, K.B. (Kirsten), Muir, K.R. (K.), Mulligan, A.-M. (Anna-Marie), Nathanson, K.L. (Katherine), Ness, R.B. (Roberta), Neuhausen, S.L. (Susan), Nevanlinna, H. (Heli), Nord, S. (Silje), Nussbaum, R.L. (Robert L.), Odunsi, K. (Kunle), Offit, K. (Kenneth), Olah, E., Olopade, O.I. (Olufunmilayo I.), Olson, J.E. (Janet), Olswold, C. (Curtis), O'Malley, D.M. (David M.), Orlow, I. (Irene), Orr, N. (Nick), Osorio, A. (Ana), Park, S.K. (Sue Kyung), Pearce, C.L. (Celeste), Pejovic, T. (Tanja), Peterlongo, P. (Paolo), Pfeiler, G. (Georg), Phelan, C. (Catherine), Poole, E.M. (Elizabeth), Pykäs, K. (Katri), Radice, P. (Paolo), Rantala, J. (Johanna), Rashid, M.U. (Muhammad), Rennert, G. (Gad), Rhenius, V. (Valerie), Rhiem, K. (Kerstin), Risch, H. (Harvey), Rodriguez, G.C. (Gustavo), Rossing, M.A. (Mary Anne), Rudolph, A. (Anja), Salvesen, H.B. (Helga), Sangrajrang, S. (Suleeporn), Sawyer, E.J. (Elinor J.), Schildkraut, J.M. (Joellen), Schmidt, M.K. (Marjanka), Schmutzler, R.K. (Rita), Sellers, T.A. (Thomas A.), Seynaeve, C.M. (Caroline), Shah, M. (Mitul), Shen, C.-Y. (Chen-Yang), Shu, X.-O. (Xiao-Ou), Sieh, W. (Weiva), Singer, C.F. (Christian), Sinilnikova, O. (Olga), Slager, S. (Susan), Song, H. (Honglin), Soucy, P. (Penny), Southey, M.C. (Melissa), Stenmark-Askmalm, M. (Marie), Stoppa-Lyonnet, D. (Dominique), Sutter, C. (Christian), Swerdlow, A.J. (Anthony ), Tchatchou, S. (Sandrine), Teixeira, P.J., Teo, S.-H. (Soo-Hwang), Terry, K.L. (Kathryn), Terry, M.B. (Mary Beth), Thomassen, M. (Mads), Tibiletti, M.G. (Maria Grazia), Tihomirova, L. (Laima), Tognazzo, S. (Silvia), Toland, A.E. (Amanda), Tomlinson, I.P. (Ian), Torres, D. (Diana), Truong, T. (Thérèse), Tseng, C.-C. (Chiu-Chen), Tung, N. (Nadine), Tworoger, S.S. (Shelley S.), Vachon, C. (Celine), Van Den Ouweland, A.M.W. (Ans M.W.), Van Doorn, H.C. (Helena C.), Rensburg, E.J. (Elizabeth) van, Veer, L.J. (Laura) van 't, Vanderstichele, A. (Adriaan), Vergote, I. (Ignace), Vijai, J. (Joseph), Wang, Q. (Qin), Wang-Gohrke, S. (Shan), Weitzel, J.N. (Jeffrey), Wentzensen, N. (N.), Whittemore, A.S. (Alice), Wildiers, H. (Hans), Winqvist, R. (Robert), Wu, A.H. (Anna), Yannoukakos, D. (Drakoulis), Yoon, S.-Y. (Sook-Yee), Yu, J-C. (Jyh-Cherng), Zheng, W. (Wei), Zheng, Y. (Ying), Khanna, K.K. (Kum Kum), Simard, J. (Jacques), Monteiro, A.N.A. (Alvaro N.), French, J.D. (Juliet), Couch, F.J. (Fergus), Freedman, M. (Matthew), Easton, D.F. (Douglas F.), Dunning, A.M. (Alison), Pharoah, P.D.P. (Paul), Edwards, S.L. (Stacey), Chenevix-Trench, G. (Georgia), Antoniou, A.C. (Antonis), Gayther, S.A. (Simon), Bowtell, D. (David), DeFazio, A. (Anna), Webb, P. (Penny), Collonge-Rame, M.-A., Damette, A. (Alexandre), Barouk-Simonet, E. (Emmanuelle), Bonnet, F. (Françoise), Bubien, V. (Virginie), Sevenet, N. (Nicolas), Longy, M. (Michel), Berthet, P. (Pascaline), Vaur, D. (Dominique), Castera, L. (Laurent), Ferrer, S.F., Bignon, Y.-J. (Yves-Jean), Uhrhammer, N. (Nancy), Coron, F. (Fanny), Faivre, L. (Laurence), Baurand, A. (Amandine), Jacquot, C. (Caroline), Bertolone, G. (Geoffrey), Lizard, S. (Sarab), Leroux, D. (Dominique), Dreyfus, H. (Hélène), Rebischung, C. (Christine), Peysselon, M. (Magalie), Peyrat, J.-P., Fournier, J. (Joëlle), Révillion, F. (Françoise), Adenis, C. (Claude), Vénat-Bouvet, L. (Laurence), Léone, M. (Mélanie), Boutry-Kryza, N. (N.), Calender, A. (Alain), Giraud, S. (Sophie), Verny-Pierre, C. (Carole), Lasset, C. (Christine), Bonadona, V. (Valérie), Barjhoux, L. (Laure), Sobol, H. (Hagay), Bourdon, V. (Violaine), Noguchi, T. (Tetsuro), Remenieras, A. (Audrey), Coupier, I. (Isabelle), Pujol, P. (Pascal), Sokolowska, J. (Johanna), Bronner, M. (Myriam), Delnatte, C.D. (Capucine), Bézieau, S. (Stéphane), Mari, V. (Véronique), Gauthier-Villars, M. (Marion), Buecher, B. (Bruno), Rouleau, E. (Etienne), Golmard, L. (Lisa), Moncoutier, V. (Virginie), Belotti, M. (Muriel), Pauw, A. (Antoine) de, Elan, C. (Camille), Fourme, E. (Emmanuelle), Birot, A.-M. (Anne-Marie), Saule, C. (Claire), Laurent, M. (Maïté), Houdayer, C. (Claude), Lesueur, F. (Fabienne), Mebirouk, N. (Noura), Coulet, F. (Florence), Colas, C. (Chrystelle), Soubrier, F., Warcoin, M. (Mathilde), Prieur, F. (Fabienne), Lebrun, M. (Marine), Kientz, C. (Caroline), Muller, D.W. (Danièle), Fricker, J.P. (Jean Pierre), Toulas, C. (Christine), Guimbaud, R. (Rosine), Gladieff, L. (Laurence), Feillel, V. (Viviane), Mortemousque, I. (Isabelle), Bressac-de Paillerets, B. (Brigitte), Caron, O. (Olivier), Guillaud-Bataille, M. (Marine), Gregory, H. (Helen), Miedzybrodzka, Z. (Zosia), Morrison, P.J. (Patrick), Donaldson, A. (Alan), Rogers, M.T. (Mark), Kennedy, M.J. (John), Porteous, M.E. (Mary), Brady, A. (A.), Barwell, J. (Julian), Foo, C. (Claire), Lalloo, F. (Fiona), Side, L. (Lucy), Eason, J. (Jacqueline), Henderson, A. (Alex), Walker, L.J. (Lisa), Cook, J. (Jackie), Snape, K. (Katie), Murray, A. (Alexandra), McCann, E. (Emma), Rookus, M.A. (Matti), Leeuwen, F.E. (Flora) van, Kolk, L.E. (Lizet) van der, Russell, N.S. (Nicola), Lange, J.L. (J.) de, Wijnands, R., Collée, J.M. (Margriet), Hooning, M.J. (Maartje), Seynaeve, C., Deurzen, C.H.M. (Carolien) van, Obdeijn, A.I.M. (Inge-Marie), Asperen, C.J. (Christi) van, Tollenaar, R.A.E.M. (Rob), Cronenburg, T.C.T.E.F. van, Kets, C.M. (Marleen), Ausems, M.G.E.M. (Margreet), Pol, C. (Carmen) van der, Os, T.A.M. (Theo) van, Waisfisz, Q. (Quinten), Meijers-Heijboer, E.J. (Hanne), Gómez García, E.B. (Encarna), Oosterwijk, J.C. (Jan), Mourits, M.J. (Marjan), Bock, G.H. (Geertruida) de, Vasen, H. (Hans), Siesling, S., Verloop, J., Overbeek, L.I.H. (Lucy), Fox, S.B. (Stephen), Kirk, J. (Judy), Lindeman, G.J. (Geoffrey), Price, M. (Melanie), Lawrenson, K. (Kate), Kar, S. (Siddhartha), McCue, K. (Karen), Kuchenbaeker, K. (Karoline), Michailidou, K. (Kyriaki), Tyrer, J.P. (Jonathan), Beesley, J. (Jonathan), Ramus, S.J. (Susan), Li, Q. (Qiyuan), Delgado, M.K. (Melissa K.), Lee, J.M. (Janet M.), Aittomäki, K. (Kristiina), Andrulis, I.L. (Irene), Anton-Culver, H. (Hoda), Arndt, V. (Volker), Arun, B.K. (Banu), Arver, B. (Brita Wasteson), Bandera, E.V. (Elisa), Barile, M. (Monica), Barkardottir, R.B. (Rosa B.), Barrowdale, D. (Daniel), Beckmann, M.W. (Matthias), Benítez, J. (Javier), Berchuck, A. (Andrew), Bisogna, M. (Maria), Bjorge, L. (Line), Blomqvist, C. (Carl), Blot, W.J. (William), Bogdanova, N.V. (Natalia), Bojesen, A. (Anders), Bojesen, S.E. (Stig), Bolla, M.K. (Manjeet K.), Bonnani, B. (Bernardo), Borresen-Dale, A.-L. (Anne-Lise), Brauch, H. (Hiltrud), Brennan, P. (Paul), Brenner, H. (Hermann), Bruinsma, F. (Fiona), Brunet, J. (Joan), Buhari, S.A.B.S. (Shaik Ahmad Bin Syed), Burwinkel, B. (Barbara), Butzow, R. (Ralf), Buys, S.S. (Saundra), Cai, Q. (Qiuyin), Caldes, T. (Trinidad), Campbell, I. (Ian), Canniotto, R. (Rikki), Chang-Claude, J. (Jenny), Chiquette, J. (Jocelyne), Choi, J.-Y. (Ji-Yeob), Claes, K.B.M. (Kathleen B.M.), Cook, L.S. (Linda S.), Cox, A. (Angela), Cramer, D.W. (Daniel), Cross, S.S. (Simon), Cybulski, C. (Cezary), Czene, K. (Kamila), Daly, M.B. (Mary B.), Damiola, F. (Francesca), Dansonka-Mieszkowska, A. (Agnieszka), Darabi, H. (Hatef), Dennis, J. (Joe), Devilee, P. (Peter), Díez, O. (Orland), Doherty, J.A. (Jennifer A.), Domchek, S.M. (Susan), Dorfling, C.M. (Cecilia), Dörk, T. (Thilo), Dumont, M. (Martine), Ehrencrona, H. (Hans), Ejlertsen, B. (Bent), Ellis, S.D. (Steve), Engel, C. (Christoph), Lee, E. (Eunjung), Evans, D.G. (D. Gareth), Fasching, P.A. (Peter), Feliubadaló, L. (L.), Figueroa, J.D. (Jonine), Flesch-Janys, D. (Dieter), Fletcher, O. (Olivia), Flyger, H. (Henrik), Foretova, L. (Lenka), Fostira, F. (Florentia), Foulkes, W.D. (William), Fridley, B.L. (Brooke), Friedman, E. (Eitan), Frost, D. (Debra), Gambino, G. (Gaetana), Ganz, P.A. (Patricia A.), Garber, J. (Judy), García-Closas, M. (Montserrat), Gentry-Maharaj, A. (Aleksandra), Ghoussaini, M. (Maya), Giles, G.G. (Graham), Glasspool, R. (Rosalind), Godwin, A.K. (Andrew K.), Goldberg, M.S. (Mark), Goldgar, D. (David), González-Neira, A. (Anna), Goode, E.L. (Ellen), Goodman, M.T. (Marc), Greene, M.H. (Mark H.), Gronwald, J. (Jacek), Guénel, P. (Pascal), Haiman, C.A. (Christopher A.), Hall, P. (Per), Hallberg, E. (Emily), Hamann, U. (Ute), Hansen, T.V.O. (Thomas), harrington, P. (Patricia), Hartman, J.M. (Joost), Hassan, N. (Norhashimah), Healey, S. (Sue), Heitz, P.U., Herzog, J. (Josef), Høgdall, E. (Estrid), Høgdall, C.K. (Claus), Hogervorst, F.B.L. (Frans), Hollestelle, A. (Antoinette), Hopper, J.L. (John), Hulick, P.J. (Peter), Huzarski, T. (Tomasz), Imyanitov, E.N. (Evgeny), Isaacs, C. (Claudine), Ito, H. (Hidemi), Jakubowska, A. (Anna), Janavicius, R. (Ramunas), Jensen, A. (Allan), John, E.M. (Esther), Johnson, N. (Nichola), Kabisch, M. (Maria), Kang, D. (Daehee), Kapuscinski, M.K. (Miroslav K.), Karlan, B.Y. (Beth Y.), Khan, S. (Sofia), Kiemeney, L.A.L.M. (Bart), Kjaer, M. (Michael), Knight, J.A. (Julia), Konstantopoulou, I. (I.), Kosma, V-M. (Veli-Matti), Kristensen, V. (Vessela), Kupryjanczyk, J. (Jolanta), Kwong, A. (Ava), Hoya, M. (Miguel) de La, Laitman, Y. (Yael), Lambrechts, D. (Diether), Le, N.D. (Nhu D.), De Leeneer, K. (Kim), Lester, K.J. (Kathryn), Levine, D.A. (Douglas), Li, J. (Jingmei), Lindblom, A. (Annika), Long, J. (Jirong), Lophatananon, A. (Artitaya), Loud, J.T. (Jennifer), Lu, K.H. (Karen), Lubinski, J. (Jan), Mannermaa, A. (Arto), Manoukian, S. (Siranoush), Le Marchand, L. (Loic), Margolin, S. (Sara), Marme, F. (Frederick), Massuger, L.F. (Leon), Matsuo, K. (Keitaro), Mazoyer, S. (Sylvie), McGuffog, L. (Lesley), McLean, C.A. (Catriona Ann), McNeish, I. (Iain), Meindl, A. (Alfons), Menon, U. (Usha), Mensenkamp, A.R. (Arjen R.), Milne, R.L. (Roger), Montagna, M. (Marco), Moysich, K.B. (Kirsten), Muir, K.R. (K.), Mulligan, A.-M. (Anna-Marie), Nathanson, K.L. (Katherine), Ness, R.B. (Roberta), Neuhausen, S.L. (Susan), Nevanlinna, H. (Heli), Nord, S. (Silje), Nussbaum, R.L. (Robert L.), Odunsi, K. (Kunle), Offit, K. (Kenneth), Olah, E., Olopade, O.I. (Olufunmilayo I.), Olson, J.E. (Janet), Olswold, C. (Curtis), O'Malley, D.M. (David M.), Orlow, I. (Irene), Orr, N. (Nick), Osorio, A. (Ana), Park, S.K. (Sue Kyung), Pearce, C.L. (Celeste), Pejovic, T. (Tanja), Peterlongo, P. (Paolo), Pfeiler, G. (Georg), Phelan, C. (Catherine), Poole, E.M. (Elizabeth), Pykäs, K. (Katri), Radice, P. (Paolo), Rantala, J. (Johanna), Rashid, M.U. (Muhammad), Rennert, G. (Gad), Rhenius, V. (Valerie), Rhiem, K. (Kerstin), Risch, H. (Harvey), Rodriguez, G.C. (Gustavo), Rossing, M.A. (Mary Anne), Rudolph, A. (Anja), Salvesen, H.B. (Helga), Sangrajrang, S. (Suleeporn), Sawyer, E.J. (Elinor J.), Schildkraut, J.M. (Joellen), Schmidt, M.K. (Marjanka), Schmutzler, R.K. (Rita), Sellers, T.A. (Thomas A.), Seynaeve, C.M. (Caroline), Shah, M. (Mitul), Shen, C.-Y. (Chen-Yang), Shu, X.-O. (Xiao-Ou), Sieh, W. (Weiva), Singer, C.F. (Christian), Sinilnikova, O. (Olga), Slager, S. (Susan), Song, H. (Honglin), Soucy, P. (Penny), Southey, M.C. (Melissa), Stenmark-Askmalm, M. (Marie), Stoppa-Lyonnet, D. (Dominique), Sutter, C. (Christian), Swerdlow, A.J. (Anthony ), Tchatchou, S. (Sandrine), Teixeira, P.J., Teo, S.-H. (Soo-Hwang), Terry, K.L. (Kathryn), Terry, M.B. (Mary Beth), Thomassen, M. (Mads), Tibiletti, M.G. (Maria Grazia), Tihomirova, L. (Laima), Tognazzo, S. (Silvia), Toland, A.E. (Amanda), Tomlinson, I.P. (Ian), Torres, D. (Diana), Truong, T. (Thérèse), Tseng, C.-C. (Chiu-Chen), Tung, N. (Nadine), Tworoger, S.S. (Shelley S.), Vachon, C. (Celine), Van Den Ouweland, A.M.W. (Ans M.W.), Van Doorn, H.C. (Helena C.), Rensburg, E.J. (Elizabeth) van, Veer, L.J. (Laura) van 't, Vanderstichele, A. (Adriaan), Vergote, I. (Ignace), Vijai, J. (Joseph), Wang, Q. (Qin), Wang-Gohrke, S. (Shan), Weitzel, J.N. (Jeffrey), Wentzensen, N. (N.), Whittemore, A.S. (Alice), Wildiers, H. (Hans), Winqvist, R. (Robert), Wu, A.H. (Anna), Yannoukakos, D. (Drakoulis), Yoon, S.-Y. (Sook-Yee), Yu, J-C. (Jyh-Cherng), Zheng, W. (Wei), Zheng, Y. (Ying), Khanna, K.K. (Kum Kum), Simard, J. (Jacques), Monteiro, A.N.A. (Alvaro N.), French, J.D. (Juliet), Couch, F.J. (Fergus), Freedman, M. (Matthew), Easton, D.F. (Douglas F.), Dunning, A.M. (Alison), Pharoah, P.D.P. (Paul), Edwards, S.L. (Stacey), Chenevix-Trench, G. (Georgia), Antoniou, A.C. (Antonis), Gayther, S.A. (Simon), Bowtell, D. (David), DeFazio, A. (Anna), Webb, P. (Penny), Collonge-Rame, M.-A., Damette, A. (Alexandre), Barouk-Simonet, E. (Emmanuelle), Bonnet, F. (Françoise), Bubien, V. (Virginie), Sevenet, N. (Nicolas), Longy, M. (Michel), Berthet, P. (Pascaline), Vaur, D. (Dominique), Castera, L. (Laurent), Ferrer, S.F., Bignon, Y.-J. (Yves-Jean), Uhrhammer, N. (Nancy), Coron, F. (Fanny), Faivre, L. (Laurence), Baurand, A. (Amandine), Jacquot, C. (Caroline), Bertolone, G. (Geoffrey), Lizard, S. (Sarab), Leroux, D. (Dominique), Dreyfus, H. (Hélène), Rebischung, C. (Christine), Peysselon, M. (Magalie), Peyrat, J.-P., Fournier, J. (Joëlle), Révillion, F. (Françoise), Adenis, C. (Claude), Vénat-Bouvet, L. (Laurence), Léone, M. (Mélanie), Boutry-Kryza, N. (N.), Calender, A. (Alain), Giraud, S. (Sophie), Verny-Pierre, C. (Carole), Lasset, C. (Christine), Bonadona, V. (Valérie), Barjhoux, L. (Laure), Sobol, H. (Hagay), Bourdon, V. (Violaine), Noguchi, T. (Tetsuro), Remenieras, A. (Audrey), Coupier, I. (Isabelle), Pujol, P. (Pascal), Sokolowska, J. (Johanna), Bronner, M. (Myriam), Delnatte, C.D. (Capucine), Bézieau, S. (Stéphane), Mari, V. (Véronique), Gauthier-Villars, M. (Marion), Buecher, B. (Bruno), Rouleau, E. (Etienne), Golmard, L. (Lisa), Moncoutier, V. (Virginie), Belotti, M. (Muriel), Pauw, A. (Antoine) de, Elan, C. (Camille), Fourme, E. (Emmanuelle), Birot, A.-M. (Anne-Marie), Saule, C. (Claire), Laurent, M. (Maïté), Houdayer, C. (Claude), Lesueur, F. (Fabienne), Mebirouk, N. (Noura), Coulet, F. (Florence), Colas, C. (Chrystelle), Soubrier, F., Warcoin, M. (Mathilde), Prieur, F. (Fabienne), Lebrun, M. (Marine), Kientz, C. (Caroline), Muller, D.W. (Danièle), Fricker, J.P. (Jean Pierre), Toulas, C. (Christine), Guimbaud, R. (Rosine), Gladieff, L. (Laurence), Feillel, V. (Viviane), Mortemousque, I. (Isabelle), Bressac-de Paillerets, B. (Brigitte), Caron, O. (Olivier), Guillaud-Bataille, M. (Marine), Gregory, H. (Helen), Miedzybrodzka, Z. (Zosia), Morrison, P.J. (Patrick), Donaldson, A. (Alan), Rogers, M.T. (Mark), Kennedy, M.J. (John), Porteous, M.E. (Mary), Brady, A. (A.), Barwell, J. (Julian), Foo, C. (Claire), Lalloo, F. (Fiona), Side, L. (Lucy), Eason, J. (Jacqueline), Henderson, A. (Alex), Walker, L.J. (Lisa), Cook, J. (Jackie), Snape, K. (Katie), Murray, A. (Alexandra), McCann, E. (Emma), Rookus, M.A. (Matti), Leeuwen, F.E. (Flora) van, Kolk, L.E. (Lizet) van der, Russell, N.S. (Nicola), Lange, J.L. (J.) de, Wijnands, R., Collée, J.M. (Margriet), Hooning, M.J. (Maartje), Seynaeve, C., Deurzen, C.H.M. (Carolien) van, Obdeijn, A.I.M. (Inge-Marie), Asperen, C.J. (Christi) van, Tollenaar, R.A.E.M. (Rob), Cronenburg, T.C.T.E.F. van, Kets, C.M. (Marleen), Ausems, M.G.E.M. (Margreet), Pol, C. (Carmen) van der, Os, T.A.M. (Theo) van, Waisfisz, Q. (Quinten), Meijers-Heijboer, E.J. (Hanne), Gómez García, E.B. (Encarna), Oosterwijk, J.C. (Jan), Mourits, M.J. (Marjan), Bock, G.H. (Geertruida) de, Vasen, H. (Hans), Siesling, S., Verloop, J., Overbeek, L.I.H. (Lucy), Fox, S.B. (Stephen), Kirk, J. (Judy), Lindeman, G.J. (Geoffrey), and Price, M. (Melanie)
Abstract: A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
Published: 2016
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45. BRCA2 Polymorphic Stop Codon K3326X and the Risk of Breast, Prostate, and Ovarian Cancers

Author: Meeks, H.D. (Huong D.), Song, H. (Honglin), Michailidou, K. (Kyriaki), Bolla, M.K. (Manjeet), Dennis, J. (Joe), Wang, Q. (Qing), Barrowdale, D. (Daniel), Frost, D. (Debra), McGuffog, L. (Lesley), Ellis, S.D. (Steve), Feng, B. (Bingjian), Buys, S.S. (Saundra), Hopper, J.L. (John), Southey, M.C. (Melissa), Tesoriero, A. (Andrea), James, M. (Margaret), Bruinsma, F. (Fiona), Campbell, I. (Ian), Broeks, A. (Annegien), Schmidt, M.K. (Marjanka), Hogervorst, F.B.L. (Frans), Beckmann, M.W. (Matthias), Fasching, P.A. (Peter), Fletcher, O. (Olivia), Johnson, N. (Nichola), Sawyer, E.J. (Elinor), Riboli, E. (Elio), Banerjee, S. (Susana), Menon, U. (Usha), Tomlinson, I. (Ian), Burwinkel, B. (Barbara), Hamann, U. (Ute), Marme, F. (Federick), Rudolph, A. (Anja), Janavicius, R. (Ramunas), Tihomirova, L. (Laima), Tung, N. (Nadine), Garber, J. (Judy), Cramer, D. (Daniel), Terry, K.L. (Kathryn), Poole, E.M. (Elizabeth), Tworoger, S. (Shelley), Dorfling, C.M. (Cecilia), Rensburg, E.J. (Elizabeth) van, Godwin, A.K. (Andrew K.), Guénel, P. (Pascal), Truong, T. (Thérèse), Stoppa-Lyonnet, D. (Dominique), Damiola, F. (Francesca), Mazoyer, S. (Sylvie), Sinilnikova, O. (Olga), Isaacs, C. (Claudine), Maugard, C., Bojesen, S.E. (Stig), Flyger, H. (Henrik), Gerdes, A-M. (Anne-Marie), Hansen, T.V.O. (Thomas), Jensen, A. (Allen), Kjaer, M. (Michael), Høgdall, C.K. (Claus), Høgdall, E. (Estrid), Pedersen, I.S. (Inge Sokilde), Thomassen, M. (Mads), Benítez, J. (Javier), González-Neira, A. (Anna), Osorio, A. (Ana), Hoya, M.D.L. (Miguel De La), Segura, P.P. (Pedro Perez), Díez, O. (Orland), Lázaro, C. (Conxi), Brunet, J. (Joan), Anton-Culver, H. (Hoda), Eunjung, L. (Lee), John, E.M. (Esther), Neuhausen, S.L. (Susan), Ding, Y.C. (Yuan), Castillo, D. (Danielle), Weitzel, J.N. (Jeffrey), Ganz, P.A. (Patricia A.), Nussbaum, R. (Robert), Chan, S. (Salina), Karlan, B.Y. (Beth Y.), Lester, K.J. (Kathryn), Wu, A. (Anna), Gayther, S.A. (Simon), Ramus, S.J. (Susan), Sieh, W. (Weiva), Whittermore, A.S. (Alice S.), Monteiro, A.N.A. (Alvaro N.A.), Phelan, C. (Catherine), Terry, M.B. (Mary Beth), Piedmonte, M. (Marion), Offit, K. (Kenneth), Robson, M. (Mark), Levine, D.A. (Douglas), Moysich, K.B. (Kirsten B.), Cannioto, R. (Rikki), Olson, S.H. (Sara), Daly, M.B. (Mary B.), Nathanson, K.L. (Katherine), Domchek, S.M. (Susan), Lu, K.H. (Karen), Liang, D. (Dong), Hildebrant, M.A.T. (Michelle A.T.), Ness, R.B. (Roberta), Modugno, F. (Francesmary), Pearce, L. (Leigh), Goodman, M.T. (Marc T.), Thompson, P.J. (Pamela J.), Brenner, H. (Hermann), Butterbach, K. (Katja), Meindl, A. (Alfons), Hahnen, E. (Eric), Wapenschmidt, B. (Barbara), Brauch, H. (Hiltrud), Brüning, T. (Thomas), Blomqvist, C. (Carl), Khan, S. (Sofia), Nevanlinna, H. (Heli), Pelttari, L.M. (Liisa), Aittomäki, K. (Kristiina), Butzow, R. (Ralf), Bogdanova, N.V. (Natalia), Dörk, T. (Thilo), Lindblom, A. (Annika), Margolin, S. (Sara), Rantala, J. (Johanna), Kosma, V-M. (Veli-Matti), Mannermaa, A. (Arto), Lambrechts, D. (Diether), Neven, P. (Patrick), Claes, K.B.M. (Kathleen B.M.), Van Maerken, T. (Tom), Chang-Claude, J. (Jenny), Flesch-Janys, D. (Dieter), Heitz, P.U., Varon-Mateeva, R. (Raymonda), Peterlongo, P. (Paolo), Radice, P. (Paolo), Viel, A. (Alessandra), Barile, M. (Monica), Peissel, B. (Bernard), Manoukian, S. (Siranoush), Montagna, M. (Marco), Oliani, C. (Cristina), Peixoto, A. (Ana), Teixeira, P.J., Collavoli, A. (Anita), Hallberg, B. (Boubou), Olson, J.E. (Janet), Goode, E.L. (Ellen L.), Hart, S.N. (Steven N.), Shimelis, H. (Hermela), Cunningham, J.M. (Julie), Giles, G.G. (Graham), Milne, R.L. (Roger), Healey, S. (Sue), Tucker, K. (Kathy), Haiman, C.A. (Christopher A.), Henderson, B.E. (Brian), Goldberg, M.S. (Mark), Tischkowitz, M. (Marc), Simard, J. (Jacques), Soucy, P. (Penny), Eccles, D. (Diana), Le, N. (Nhu), Borresen-Dale, A.-L. (Anne-Lise), Kristensen, V. (Vessela), Salvesen, H.B. (Helga), Bjorge, L. (Line), Bandera, E.V. (Elisa), Risch, H. (Harvey), Zheng, W. (Wei), Beeghly-Fadiel, A. (Alicia), Cai, H. (Hui), Pykäs, K. (Katri), Tollenaar, R.A.E.M. (Rob), Ouweland, A.M.W. (Ans) van den, Andrulis, I.L. (Irene), Knight, J.A. (Julia A.), Narod, S. (Steven), Devilee, P. (Peter), Winqvist, R. (Robert), Figueroa, J.D. (Jonine), Greene, M.H. (Mark H.), Mai, P.L. (Phuong), Loud, J.T. (Jennifer), García-Closas, M. (Montserrat), Schoemaker, M. (Minouk), Czene, K. (Kamila), Darabi, H. (Hatef), McNeish, I. (Iain), Siddiquil, N. (Nadeem), Glasspool, R. (Rosalind), Kwong, A. (Ava), Park, S.K. (Sue K.), Teo, S.-H. (Soo-Hwang), Yoon, S.-Y. (Sook-Yee), Matsuo, K. (Keitaro), Hosono, N. (Naoya), Woo, Y.L. (Yin Ling), Gao, Y. (Ying), Foretova, L. (Lenka), Singer, C.F. (Christian), Rappaport-Feurhauser, C. (Christine), Friedman, E. (Eitan), Laitman, Y. (Yael), Rennert, G. (Gad), Imyanitov, E.N. (Evgeny), Hulick, P.J. (Peter), Olopade, O.I. (Olufunmilayo I.), Senter, L. (Leigha), Olah, E. (Edith), Doherty, J.A. (Jennifer A.), Schildkraut, J.M. (Joellen), Koppert, L.B. (Linetta), Kiemeney, L.A.L.M. (Bart), Massuger, L.F. (Leon), Cook, L.S. (Linda S.), Pejovic, T. (Tanja), Li, J. (Jingmei), Borg, Å. (Åke), Öfverholm, A. (Anna), Rossing, M.A. (Mary Anne), Wentzensen, N. (N.), Henriksson, K. (Karin), Cox, A. (Angela), Cross, S.S. (Simon), Pasini, B. (Barbara), Shah, M. (Mitul), Kabisch, M. (Maria), Torres, D. (Diana), Jakubowska, A. (Anna), Lubinski, J. (Jan), Gronwald, J. (Jacek), Agnarsson, B.A. (Bjarni), Kupryjanczyk, J. (Jolanta), Moes-Sosnowska, J. (Joanna), Fostira, F. (Florentia), Konstantopoulou, I. (I.), Slager, S. (Susan), Jones, M. (Michael), Antoniou, A.C. (Antonis), Berchuck, A. (Andrew), Swerdlow, A.J. (Anthony ), Chenevix-Trench, G. (Georgia), Dunning, A.M. (Alison), Pharoah, P.D.P. (Paul), Hall, P. (Per), Easton, D.F. (Douglas F.), Couch, F.J. (Fergus), Spurdle, A.B. (Amanda), Goldgar, D. (David), Meeks, H.D. (Huong D.), Song, H. (Honglin), Michailidou, K. (Kyriaki), Bolla, M.K. (Manjeet), Dennis, J. (Joe), Wang, Q. (Qing), Barrowdale, D. (Daniel), Frost, D. (Debra), McGuffog, L. (Lesley), Ellis, S.D. (Steve), Feng, B. (Bingjian), Buys, S.S. (Saundra), Hopper, J.L. (John), Southey, M.C. (Melissa), Tesoriero, A. (Andrea), James, M. (Margaret), Bruinsma, F. (Fiona), Campbell, I. (Ian), Broeks, A. (Annegien), Schmidt, M.K. (Marjanka), Hogervorst, F.B.L. (Frans), Beckmann, M.W. (Matthias), Fasching, P.A. (Peter), Fletcher, O. (Olivia), Johnson, N. (Nichola), Sawyer, E.J. (Elinor), Riboli, E. (Elio), Banerjee, S. (Susana), Menon, U. (Usha), Tomlinson, I. (Ian), Burwinkel, B. (Barbara), Hamann, U. (Ute), Marme, F. (Federick), Rudolph, A. (Anja), Janavicius, R. (Ramunas), Tihomirova, L. (Laima), Tung, N. (Nadine), Garber, J. (Judy), Cramer, D. (Daniel), Terry, K.L. (Kathryn), Poole, E.M. (Elizabeth), Tworoger, S. (Shelley), Dorfling, C.M. (Cecilia), Rensburg, E.J. (Elizabeth) van, Godwin, A.K. (Andrew K.), Guénel, P. (Pascal), Truong, T. (Thérèse), Stoppa-Lyonnet, D. (Dominique), Damiola, F. (Francesca), Mazoyer, S. (Sylvie), Sinilnikova, O. (Olga), Isaacs, C. (Claudine), Maugard, C., Bojesen, S.E. (Stig), Flyger, H. (Henrik), Gerdes, A-M. (Anne-Marie), Hansen, T.V.O. (Thomas), Jensen, A. (Allen), Kjaer, M. (Michael), Høgdall, C.K. (Claus), Høgdall, E. (Estrid), Pedersen, I.S. (Inge Sokilde), Thomassen, M. (Mads), Benítez, J. (Javier), González-Neira, A. (Anna), Osorio, A. (Ana), Hoya, M.D.L. (Miguel De La), Segura, P.P. (Pedro Perez), Díez, O. (Orland), Lázaro, C. (Conxi), Brunet, J. (Joan), Anton-Culver, H. (Hoda), Eunjung, L. (Lee), John, E.M. (Esther), Neuhausen, S.L. (Susan), Ding, Y.C. (Yuan), Castillo, D. (Danielle), Weitzel, J.N. (Jeffrey), Ganz, P.A. (Patricia A.), Nussbaum, R. (Robert), Chan, S. (Salina), Karlan, B.Y. (Beth Y.), Lester, K.J. (Kathryn), Wu, A. (Anna), Gayther, S.A. (Simon), Ramus, S.J. (Susan), Sieh, W. (Weiva), Whittermore, A.S. (Alice S.), Monteiro, A.N.A. (Alvaro N.A.), Phelan, C. (Catherine), Terry, M.B. (Mary Beth), Piedmonte, M. (Marion), Offit, K. (Kenneth), Robson, M. (Mark), Levine, D.A. (Douglas), Moysich, K.B. (Kirsten B.), Cannioto, R. (Rikki), Olson, S.H. (Sara), Daly, M.B. (Mary B.), Nathanson, K.L. (Katherine), Domchek, S.M. (Susan), Lu, K.H. (Karen), Liang, D. (Dong), Hildebrant, M.A.T. (Michelle A.T.), Ness, R.B. (Roberta), Modugno, F. (Francesmary), Pearce, L. (Leigh), Goodman, M.T. (Marc T.), Thompson, P.J. (Pamela J.), Brenner, H. (Hermann), Butterbach, K. (Katja), Meindl, A. (Alfons), Hahnen, E. (Eric), Wapenschmidt, B. (Barbara), Brauch, H. (Hiltrud), Brüning, T. (Thomas), Blomqvist, C. (Carl), Khan, S. (Sofia), Nevanlinna, H. (Heli), Pelttari, L.M. (Liisa), Aittomäki, K. (Kristiina), Butzow, R. (Ralf), Bogdanova, N.V. (Natalia), Dörk, T. (Thilo), Lindblom, A. (Annika), Margolin, S. (Sara), Rantala, J. (Johanna), Kosma, V-M. (Veli-Matti), Mannermaa, A. (Arto), Lambrechts, D. (Diether), Neven, P. (Patrick), Claes, K.B.M. (Kathleen B.M.), Van Maerken, T. (Tom), Chang-Claude, J. (Jenny), Flesch-Janys, D. (Dieter), Heitz, P.U., Varon-Mateeva, R. (Raymonda), Peterlongo, P. (Paolo), Radice, P. (Paolo), Viel, A. (Alessandra), Barile, M. (Monica), Peissel, B. (Bernard), Manoukian, S. (Siranoush), Montagna, M. (Marco), Oliani, C. (Cristina), Peixoto, A. (Ana), Teixeira, P.J., Collavoli, A. (Anita), Hallberg, B. (Boubou), Olson, J.E. (Janet), Goode, E.L. (Ellen L.), Hart, S.N. (Steven N.), Shimelis, H. (Hermela), Cunningham, J.M. (Julie), Giles, G.G. (Graham), Milne, R.L. (Roger), Healey, S. (Sue), Tucker, K. (Kathy), Haiman, C.A. (Christopher A.), Henderson, B.E. (Brian), Goldberg, M.S. (Mark), Tischkowitz, M. (Marc), Simard, J. (Jacques), Soucy, P. (Penny), Eccles, D. (Diana), Le, N. (Nhu), Borresen-Dale, A.-L. (Anne-Lise), Kristensen, V. (Vessela), Salvesen, H.B. (Helga), Bjorge, L. (Line), Bandera, E.V. (Elisa), Risch, H. (Harvey), Zheng, W. (Wei), Beeghly-Fadiel, A. (Alicia), Cai, H. (Hui), Pykäs, K. (Katri), Tollenaar, R.A.E.M. (Rob), Ouweland, A.M.W. (Ans) van den, Andrulis, I.L. (Irene), Knight, J.A. (Julia A.), Narod, S. (Steven), Devilee, P. (Peter), Winqvist, R. (Robert), Figueroa, J.D. (Jonine), Greene, M.H. (Mark H.), Mai, P.L. (Phuong), Loud, J.T. (Jennifer), García-Closas, M. (Montserrat), Schoemaker, M. (Minouk), Czene, K. (Kamila), Darabi, H. (Hatef), McNeish, I. (Iain), Siddiquil, N. (Nadeem), Glasspool, R. (Rosalind), Kwong, A. (Ava), Park, S.K. (Sue K.), Teo, S.-H. (Soo-Hwang), Yoon, S.-Y. (Sook-Yee), Matsuo, K. (Keitaro), Hosono, N. (Naoya), Woo, Y.L. (Yin Ling), Gao, Y. (Ying), Foretova, L. (Lenka), Singer, C.F. (Christian), Rappaport-Feurhauser, C. (Christine), Friedman, E. (Eitan), Laitman, Y. (Yael), Rennert, G. (Gad), Imyanitov, E.N. (Evgeny), Hulick, P.J. (Peter), Olopade, O.I. (Olufunmilayo I.), Senter, L. (Leigha), Olah, E. (Edith), Doherty, J.A. (Jennifer A.), Schildkraut, J.M. (Joellen), Koppert, L.B. (Linetta), Kiemeney, L.A.L.M. (Bart), Massuger, L.F. (Leon), Cook, L.S. (Linda S.), Pejovic, T. (Tanja), Li, J. (Jingmei), Borg, Å. (Åke), Öfverholm, A. (Anna), Rossing, M.A. (Mary Anne), Wentzensen, N. (N.), Henriksson, K. (Karin), Cox, A. (Angela), Cross, S.S. (Simon), Pasini, B. (Barbara), Shah, M. (Mitul), Kabisch, M. (Maria), Torres, D. (Diana), Jakubowska, A. (Anna), Lubinski, J. (Jan), Gronwald, J. (Jacek), Agnarsson, B.A. (Bjarni), Kupryjanczyk, J. (Jolanta), Moes-Sosnowska, J. (Joanna), Fostira, F. (Florentia), Konstantopoulou, I. (I.), Slager, S. (Susan), Jones, M. (Michael), Antoniou, A.C. (Antonis), Berchuck, A. (Andrew), Swerdlow, A.J. (Anthony ), Chenevix-Trench, G. (Georgia), Dunning, A.M. (Alison), Pharoah, P.D.P. (Paul), Hall, P. (Per), Easton, D.F. (Douglas F.), Couch, F.J. (Fergus), Spurdle, A.B. (Amanda), and Goldgar, D. (David)
Abstract: Background: The K3326X variant in BRCA2 (BRCA2∗c.9976A>T p.Lys3326∗rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormonerelated cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76637 cancer case patients and 83796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9×10-6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8×10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor-negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4×10-5 and ORw = 1.50, 95% CI = 1.28 to
Published: 2016
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46. Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression: identification of a modifier of breast cancer risk at locus 11q22.3

Author: Hamdi, Y. (Yosr), Soucy, P. (Penny), Kuchenbaeker, K.B. (Karoline B.), Pastinen, T. (Tomi), Droit, A. (Arnaud), Lemaçon, A. (Audrey), Adlard, J.W. (Julian), Aittomäki, K. (Kristiina), Andrulis, I.L. (Irene), Arason, A. (Adalgeir), Arnold, N. (Norbert), Arun, B.K. (Banu), Azzollini, J., Bane, A.L. (Anita L.), Barjhoux, L. (Laure), Barrowdale, D. (Daniel), Benítez, J. (Javier), Berthet, P. (Pascaline), Blok, M.J. (Marinus), Bobolis, K.A. (Kristie A.), Bonadona, V. (Valérie), Bonnani, B. (Bernardo), Bradbury, A.R. (Angela R.), Brewer, C. (Carole), Buecher, B. (Bruno), Buys, S.S. (Saundra S.), Caligo, M.A. (Maria), Chiquette, J. (Jocelyne), Chung, W. (Wendy), Claes, K.B.M. (Kathleen B.M.), Daly, M.B. (Mary B.), Damiola, F. (Francesca), Davidson, R. (Rosemarie), Hoya, M. (Miguel) de La, De Leeneer, K. (Kim), Díez, O. (Orland), Ding, Y.C. (Yuan), Dolcetti, R. (Riccardo), Domchek, S.M. (Susan), Dorfling, C.M. (Cecilia), Eccles, D. (Diana), Eeles, R. (Ros), Einbeigi, Z. (Zakaria), Ejlertsen, B. (Bent), EMBRACE, Engel, C. (Christoph), Gareth Evans, D., Feliubadaló, L. (L.), Foretova, L. (Lenka), Fostira, F. (Florentia), Foulkes, W.D. (William D.), Fountzilas, G. (George), Friedman, E. (Eitan), Frost, D. (Debra), Ganschow, P. (Pamela), Ganz, P.A. (Patricia A.), Garber, J. (Judy), Gayther, S.A. (Simon), GEMO Study Collaborators, Gerdes, A-M. (Anne-Marie), Glendon, G. (Gord), Godwin, A.K. (Andrew K.), Goldgar, D. (David), Greene, M.H. (Mark H.), Gronwald, J. (Jacek), Hahnen, E. (Eric), Hamann, U. (Ute), Hansen, T.V.O. (Thomas), Hart, S. (Stewart), Hays, J. (John), HEBON, Hogervorst, F.B.L. (Frans), Hulick, P.J. (Peter), Imyanitov, E.N. (Evgeny), Isaacs, C. (Claudine), Izatt, L. (Louise), Jakubowska, A. (Anna), James, M. (Margaret), Janavicius, R. (Ramunas), Jensen, U.B., John, E.M. (Esther), Joseph, V. (Vijai), Just, W. (Walter), Kaczmarek, K. (Katarzyna), Karlan, B.Y. (Beth Y.), KConFab Investigators, Kets, C.M. (Marleen), Kirk, J. (Judy), Kriege, M. (Mieke), Laitman, Y. (Yael), Laurent, M. (Maïté), Lázaro, C. (Conxi), Leslie, G. (Goska), Lester, K.J. (Kathryn), Lesueur, F. (Fabienne), Liljegren, A. (Annelie), Loman, N. (Niklas), Loud, J.T. (Jennifer), Manoukian, S. (Siranoush), Mariani, M. (Milena), Mazoyer, S. (Sylvie), McGuffog, L. (Lesley), Meijers-Heijboer, E.J. (Hanne), Meindl, A. (Alfons), Miller, A. (Austin), Montagna, M. (Marco), Mulligan, A.-M. (Anna-Marie), Nathanson, K.L. (Katherine), Neuhausen, S.L. (Susan), Nevanlinna, H. (Heli), Nussbaum, R.L. (Robert L.), Olah, E. (Edith), Olopade, O.I. (Olufunmilayo I.), Ong, K.-R. (Kai-Ren), Oosterwijk, J.C. (Jan), Osorio, A. (Ana), Papi, L. (Laura), Park, S.K. (Sue K.), Pedersen, I.S. (Inge Sokilde), Peissel, B. (Bernard), Segura, P.P. (Pedro Perez), Peterlongo, P. (Paolo), Phelan, C. (Catherine), Radice, P. (Paolo), Rantala, J. (Johanna), Rappaport-Fuerhauser, C. (Christine), Rennert, G. (Gad), Richardson, A.L. (Andrea), Robson, M. (Mark), Rodriguez, G.C. (Gustavo), Rookus, M.A. (Matti), Schmutzler, R.K. (Rita), Sevenet, N. (Nicolas), Shah, P.D. (Payal D.), Singer, C.F. (Christian), Slavin, T.P. (Thomas P.), Snape, K. (Katie), Sokolowska, J. (Johanna), Sønderstrup, I.M.H. (Ida Marie Heeholm), Southey, M.C. (Melissa), Spurdle, A.B. (Amanda), Stadler, Z. (Zsofia), Stoppa-Lyonnet, D. (Dominique), Sukiennicki, G. (Grzegorz), Sutter, C. (Christian), Tan, Y. (Yen), Tea, M.-K., Teixeira, P.J., Teulé, A. (A.), Teo, S.-H. (Soo-Hwang), Terry, M.B. (Mary Beth), Thomassen, M. (Mads), Tihomirova, L. (Laima), Tischkowitz, M. (Marc), Tognazzo, S. (Silvia), Toland, A.E. (Amanda), Tung, N. (Nadine), Ouweland, A.M.W. (Ans) van den, Luijt, R.B. (Rob) van der, Engelen, K. (Klaartje) van, Rensburg, E.J. (Elizabeth) van, Varon-Mateeva, R. (Raymonda), Wapenschmidt, B. (Barbara), Wijnen, J.T. (Juul), Rebbeck, R. (Timothy), Chenevix-Trench, G. (Georgia), Offit, K. (Kenneth), Couch, F.J. (Fergus J.), Nord, S. (Silje), Easton, D.F. (Douglas F.), Antoniou, A.C. (Antonis), Simard, J. (Jacques), Hamdi, Y. (Yosr), Soucy, P. (Penny), Kuchenbaeker, K.B. (Karoline B.), Pastinen, T. (Tomi), Droit, A. (Arnaud), Lemaçon, A. (Audrey), Adlard, J.W. (Julian), Aittomäki, K. (Kristiina), Andrulis, I.L. (Irene), Arason, A. (Adalgeir), Arnold, N. (Norbert), Arun, B.K. (Banu), Azzollini, J., Bane, A.L. (Anita L.), Barjhoux, L. (Laure), Barrowdale, D. (Daniel), Benítez, J. (Javier), Berthet, P. (Pascaline), Blok, M.J. (Marinus), Bobolis, K.A. (Kristie A.), Bonadona, V. (Valérie), Bonnani, B. (Bernardo), Bradbury, A.R. (Angela R.), Brewer, C. (Carole), Buecher, B. (Bruno), Buys, S.S. (Saundra S.), Caligo, M.A. (Maria), Chiquette, J. (Jocelyne), Chung, W. (Wendy), Claes, K.B.M. (Kathleen B.M.), Daly, M.B. (Mary B.), Damiola, F. (Francesca), Davidson, R. (Rosemarie), Hoya, M. (Miguel) de La, De Leeneer, K. (Kim), Díez, O. (Orland), Ding, Y.C. (Yuan), Dolcetti, R. (Riccardo), Domchek, S.M. (Susan), Dorfling, C.M. (Cecilia), Eccles, D. (Diana), Eeles, R. (Ros), Einbeigi, Z. (Zakaria), Ejlertsen, B. (Bent), EMBRACE, Engel, C. (Christoph), Gareth Evans, D., Feliubadaló, L. (L.), Foretova, L. (Lenka), Fostira, F. (Florentia), Foulkes, W.D. (William D.), Fountzilas, G. (George), Friedman, E. (Eitan), Frost, D. (Debra), Ganschow, P. (Pamela), Ganz, P.A. (Patricia A.), Garber, J. (Judy), Gayther, S.A. (Simon), GEMO Study Collaborators, Gerdes, A-M. (Anne-Marie), Glendon, G. (Gord), Godwin, A.K. (Andrew K.), Goldgar, D. (David), Greene, M.H. (Mark H.), Gronwald, J. (Jacek), Hahnen, E. (Eric), Hamann, U. (Ute), Hansen, T.V.O. (Thomas), Hart, S. (Stewart), Hays, J. (John), HEBON, Hogervorst, F.B.L. (Frans), Hulick, P.J. (Peter), Imyanitov, E.N. (Evgeny), Isaacs, C. (Claudine), Izatt, L. (Louise), Jakubowska, A. (Anna), James, M. (Margaret), Janavicius, R. (Ramunas), Jensen, U.B., John, E.M. (Esther), Joseph, V. (Vijai), Just, W. (Walter), Kaczmarek, K. (Katarzyna), Karlan, B.Y. (Beth Y.), KConFab Investigators, Kets, C.M. (Marleen), Kirk, J. (Judy), Kriege, M. (Mieke), Laitman, Y. (Yael), Laurent, M. (Maïté), Lázaro, C. (Conxi), Leslie, G. (Goska), Lester, K.J. (Kathryn), Lesueur, F. (Fabienne), Liljegren, A. (Annelie), Loman, N. (Niklas), Loud, J.T. (Jennifer), Manoukian, S. (Siranoush), Mariani, M. (Milena), Mazoyer, S. (Sylvie), McGuffog, L. (Lesley), Meijers-Heijboer, E.J. (Hanne), Meindl, A. (Alfons), Miller, A. (Austin), Montagna, M. (Marco), Mulligan, A.-M. (Anna-Marie), Nathanson, K.L. (Katherine), Neuhausen, S.L. (Susan), Nevanlinna, H. (Heli), Nussbaum, R.L. (Robert L.), Olah, E. (Edith), Olopade, O.I. (Olufunmilayo I.), Ong, K.-R. (Kai-Ren), Oosterwijk, J.C. (Jan), Osorio, A. (Ana), Papi, L. (Laura), Park, S.K. (Sue K.), Pedersen, I.S. (Inge Sokilde), Peissel, B. (Bernard), Segura, P.P. (Pedro Perez), Peterlongo, P. (Paolo), Phelan, C. (Catherine), Radice, P. (Paolo), Rantala, J. (Johanna), Rappaport-Fuerhauser, C. (Christine), Rennert, G. (Gad), Richardson, A.L. (Andrea), Robson, M. (Mark), Rodriguez, G.C. (Gustavo), Rookus, M.A. (Matti), Schmutzler, R.K. (Rita), Sevenet, N. (Nicolas), Shah, P.D. (Payal D.), Singer, C.F. (Christian), Slavin, T.P. (Thomas P.), Snape, K. (Katie), Sokolowska, J. (Johanna), Sønderstrup, I.M.H. (Ida Marie Heeholm), Southey, M.C. (Melissa), Spurdle, A.B. (Amanda), Stadler, Z. (Zsofia), Stoppa-Lyonnet, D. (Dominique), Sukiennicki, G. (Grzegorz), Sutter, C. (Christian), Tan, Y. (Yen), Tea, M.-K., Teixeira, P.J., Teulé, A. (A.), Teo, S.-H. (Soo-Hwang), Terry, M.B. (Mary Beth), Thomassen, M. (Mads), Tihomirova, L. (Laima), Tischkowitz, M. (Marc), Tognazzo, S. (Silvia), Toland, A.E. (Amanda), Tung, N. (Nadine), Ouweland, A.M.W. (Ans) van den, Luijt, R.B. (Rob) van der, Engelen, K. (Klaartje) van, Rensburg, E.J. (Elizabeth) van, Varon-Mateeva, R. (Raymonda), Wapenschmidt, B. (Barbara), Wijnen, J.T. (Juul), Rebbeck, R. (Timothy), Chenevix-Trench, G. (Georgia), Offit, K. (Kenneth), Couch, F.J. (Fergus J.), Nord, S. (Silje), Easton, D.F. (Douglas F.), Antoniou, A.C. (Antonis), and Simard, J. (Jacques)
Abstract: Purpose: Cis-acting regulatory SNPs resulting in differential allelic expression (DAE) may, in part, explain the underlying phenotypic variation associated with many complex diseases. To investigate whether common variants associated with DAE were involved in breast cancer susceptibility among BRCA1 and BRCA2 mutation carriers, a list of 175 genes was developed based of their involvement in cancer-related pathways. Methods: Using data from a genome-wide map of SNPs associated with allelic expression, we assessed the association of ~320 SNPs located in the vicinity of these genes with breast and ovarian cancer risks in 15,252 BRCA1 and 8211 BRCA2 mutation carriers ascertained from 54 studies participating in the Consortium of Investigators of Modifiers of BRCA1/2. Results: We identified a region on 11q22.3 that is significantly associated with breast cancer risk in BRCA1 mutation carriers (most significant SNP rs228595 p = 7 × 10−6). This association was absent in BRCA2 carriers (p = 0.57). The 11q22.3 region notably encompasses genes such as ACAT1, NPAT, and ATM. Expression quantitative trait loci associations were observed in both normal breast and tumors across this region, namely for ACAT1, ATM, and other genes. In silico analysis revealed some overlap between top risk-associated SNPs and relevant biological features in mammary cell data, which suggests potential functional significance. Conclusion: We identified 11q22.3 as a new modifier locus in BRCA1 carriers. Replication in larger studies using estrogen receptor (ER)-negative or triple-negative (i.e., ER-, progesterone receptor-, and HER2-negative) cases could therefore be helpful to confirm the association of
Published: 2016
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47. Inheritance of deleterious mutations at both BRCA1 and BRCA2 in an international sample of 32,295 women

Author: Rebbeck, R. (Timothy), Friebel, M.O.W. (Mark ), Mitra, N. (Nandita), Wan, F. (Fei), Chen, S. (Stephanie), Andrulis, I.L. (Irene), Apostolou, P. (Paraskevi), Arnold, N. (Norbert), Arun, B.K. (Banu), Barrowdale, D. (Daniel), Benítez, J. (Javier), Berger, R. (Raanan), Berthet, P. (Pascaline), Borg, Å. (Åke), Buys, S.S. (Saundra S.), Caldes, T. (Trinidad), Carter, J. (Jonathan), Chiquette, J. (Jocelyne), Claes, K.B.M. (Kathleen B.M.), Couch, F.J. (Fergus J.), Cybulski, C. (Cezary), Daly, M.B. (Mary), Hoya, M. (Miguel) de La, Díez, O. (Orland), Domchek, S.M. (Susan), Nathanson, K.L. (Katherine), Durda, K. (Katarzyna), Ellis, S.D. (Steve), Evans, D.G. (D.Gareth), Foretova, L. (Lenka), Friedman, E. (Eitan), Frost, D. (Debra), Ganz, P.A. (Patricia), Garber, J. (Judy), Glendon, G. (Gord), Godwin, A.K. (Andrew), Greene, M.H. (Mark), Gronwald, J. (Jacek), Hahnen, E. (Eric), Hallberg, E. (Emily), Hamann, U. (Ute), Hansen, T.V.O. (Thomas), Imyanitov, E.N. (Evgeny), Isaacs, C. (Claudine), Jakubowska, A. (Anna), Janavicius, R. (Ramunas), Jaworska-Bieniek, K. (Katarzyna), John, E.M. (Esther), Karlan, B.Y. (Beth), Kaufman, B. (Bella), Kwong, A. (Ava), Laitman, Y. (Yael), Lasset, C. (Christine), Lázaro, C. (Conxi), Lester, K.J. (Kathryn), Loman, N. (Niklas), Lubinski, J. (Jan), Manoukian, S. (Siranoush), Mitchell, G. (Gillian), Montagna, M. (Marco), Neuhausen, S.L. (Susan), Nevanlinna, H. (Heli), Niederacher, D. (Dieter), Nussbaum, R. (Robert), Offit, K. (Kenneth), Olah, E., Olopade, O.I. (Olofunmilayo), Park, S.K. (Sue K.), Piedmonte, M. (Marion), Radice, P. (Paolo), Rappaport-Fuerhauser, C. (Christine), Rookus, M.A. (Matti), Seynaeve, C.M. (Caroline), Simard, J. (Jacques), Singer, C.F. (Christian), Soucy, P. (Penny), Southey, M.C. (Melissa), Stoppa-Lyonnet, D. (Dominique), Sukiennicki, G. (Grzegorz), Szabo, C. (Csilla), Tancredi, M. (Mariella), Teixeira, P.J., Teo, S.-H. (Soo-Hwang), Terry, M.B. (Mary Beth), Thomassen, M. (Mads), Tihomirova, L. (Laima), Tischkowitz, M. (Marc), Toland, A.E. (Amanda), Toloczko-Grabarek, A. (Aleksandra), Tung, N. (Nadine), Rensburg, E.J. (Elizabeth) van, Villano, D. (Danylo), Wang-Gohrke, S. (Shan), Wapenschmidt, B. (Barbara), Weitzel, J.N. (Jeffrey), Zidan, J. (Jamal), Zorn, K.K. (Kristin K.), McGuffog, L. (Lesley), Easton, D.F. (Douglas), Chenevix-Trench, G. (Georgia), Antoniou, A.C. (Antonis), Ramus, S.J. (Susan), Rebbeck, R. (Timothy), Friebel, M.O.W. (Mark ), Mitra, N. (Nandita), Wan, F. (Fei), Chen, S. (Stephanie), Andrulis, I.L. (Irene), Apostolou, P. (Paraskevi), Arnold, N. (Norbert), Arun, B.K. (Banu), Barrowdale, D. (Daniel), Benítez, J. (Javier), Berger, R. (Raanan), Berthet, P. (Pascaline), Borg, Å. (Åke), Buys, S.S. (Saundra S.), Caldes, T. (Trinidad), Carter, J. (Jonathan), Chiquette, J. (Jocelyne), Claes, K.B.M. (Kathleen B.M.), Couch, F.J. (Fergus J.), Cybulski, C. (Cezary), Daly, M.B. (Mary), Hoya, M. (Miguel) de La, Díez, O. (Orland), Domchek, S.M. (Susan), Nathanson, K.L. (Katherine), Durda, K. (Katarzyna), Ellis, S.D. (Steve), Evans, D.G. (D.Gareth), Foretova, L. (Lenka), Friedman, E. (Eitan), Frost, D. (Debra), Ganz, P.A. (Patricia), Garber, J. (Judy), Glendon, G. (Gord), Godwin, A.K. (Andrew), Greene, M.H. (Mark), Gronwald, J. (Jacek), Hahnen, E. (Eric), Hallberg, E. (Emily), Hamann, U. (Ute), Hansen, T.V.O. (Thomas), Imyanitov, E.N. (Evgeny), Isaacs, C. (Claudine), Jakubowska, A. (Anna), Janavicius, R. (Ramunas), Jaworska-Bieniek, K. (Katarzyna), John, E.M. (Esther), Karlan, B.Y. (Beth), Kaufman, B. (Bella), Kwong, A. (Ava), Laitman, Y. (Yael), Lasset, C. (Christine), Lázaro, C. (Conxi), Lester, K.J. (Kathryn), Loman, N. (Niklas), Lubinski, J. (Jan), Manoukian, S. (Siranoush), Mitchell, G. (Gillian), Montagna, M. (Marco), Neuhausen, S.L. (Susan), Nevanlinna, H. (Heli), Niederacher, D. (Dieter), Nussbaum, R. (Robert), Offit, K. (Kenneth), Olah, E., Olopade, O.I. (Olofunmilayo), Park, S.K. (Sue K.), Piedmonte, M. (Marion), Radice, P. (Paolo), Rappaport-Fuerhauser, C. (Christine), Rookus, M.A. (Matti), Seynaeve, C.M. (Caroline), Simard, J. (Jacques), Singer, C.F. (Christian), Soucy, P. (Penny), Southey, M.C. (Melissa), Stoppa-Lyonnet, D. (Dominique), Sukiennicki, G. (Grzegorz), Szabo, C. (Csilla), Tancredi, M. (Mariella), Teixeira, P.J., Teo, S.-H. (Soo-Hwang), Terry, M.B. (Mary Beth), Thomassen, M. (Mads), Tihomirova, L. (Laima), Tischkowitz, M. (Marc), Toland, A.E. (Amanda), Toloczko-Grabarek, A. (Aleksandra), Tung, N. (Nadine), Rensburg, E.J. (Elizabeth) van, Villano, D. (Danylo), Wang-Gohrke, S. (Shan), Wapenschmidt, B. (Barbara), Weitzel, J.N. (Jeffrey), Zidan, J. (Jamal), Zorn, K.K. (Kristin K.), McGuffog, L. (Lesley), Easton, D.F. (Douglas), Chenevix-Trench, G. (Georgia), Antoniou, A.C. (Antonis), and Ramus, S.J. (Susan)
Abstract: Background: Most BRCA1 or BRCA2 mutation carriers have inherited a single (heterozygous) mutation. Transheterozygotes (TH) who have inherited deleterious mutations in both BRCA1 and BRCA2 are rare, and the consequences of transheterozygosity are poorly understood. Methods: From 32,295 female BRCA1/2 mutation carriers, we identified 93 TH (0.3 %). "Cases" were defined as TH, and "controls" were single mutations at BRCA1 (SH1) or BRCA2 (SH2). Matched SH1 "controls" carried a BRCA1 mutation found in the TH "case". Matched SH2 "controls" carried a BRCA2 mutation found in the TH "case". After matching the TH carriers with SH1 or SH2, 91 TH were matched to 9316 SH1, and 89 TH were matched to 3370 SH2. Results: The majority of TH (45.2 %) involved the three common Jewish mutations. TH were more likely than SH1 and SH2 women to have been ever diagnosed with breast cancer (BC; p = 0.002). TH were more likely to be diagnosed with ovarian cancer (OC) than SH2 (p = 0.017), but not SH1. Age at BC diagnosis was the same in TH vs. SH1 (p = 0.231), but was on average 4.5 years younger in TH than in SH2 (p < 0.001). BC in TH was more likely to be estrogen receptor (ER) positive (p = 0.010) or progesterone receptor (PR) positive (p = 0.013) than in SH1, but less likely to be ER positive (p < 0.001) or PR positive (p = 0.012) than SH2. Among 15 tumors from TH patients, there was no clear pattern of loss of heterozygosity (LOH) for BRCA1 or BRCA2 in either BC or OC. Conclusions: Our observations suggest that clinical TH phenotypes resemble SH1. However, TH breast tumor marker characteristics are phenotypically intermediate to SH1 and SH2.
Published: 2016
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48. Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus

Author: Zeng, C., Guo, X., Long, J., Kuchenbaecker, K.B., Droit, A., Michailidou, K., Ghoussaini, M., Kar, S., Freeman, A., Hopper, J.L., Milne, R.L., Bolla, M.K., Wang, Q., Dennis, J., Agata, S., Ahmed, S., Aittomaki, K., Andrulis, I.L., Anton-Culver, H., Antonenkova, N.N., Arason, A., Arndt, V., Arun, B.K., Arver, B., Bacot, F., Barrowdale, D., Baynes, C., Beeghly-Fadiel, A., Benitez, J., Bermisheva, M., Blomqvist, C., Blot, W.J., Bogdanova, N.V., Bojesen, S.E., Bonanni, B., Borresen-Dale, A.-L., Brand, J.S., Brauch, H., Brennan, P., Brenner, H., Broeks, A., Brüning, T., Burwinkel, B., Buys, S.S., Cai, Q., Caldes, T., Campbell, I., Carpenter, J., Chang-Claude, J., Choi, J.Y., Claes, K.B.M., Clarke, C., Cox, A., Cross, S.S., Czene, K., Daly, M.B., de la Hoya, M., De Leeneer, K., Devilee, P., Diez, O., Domchek, S.M., Doody, M.M., Dorfling, C.M., Dörk, T., Dos Santos Silva, I., Dumont, M., Dwek, M., Dworniczak, B., Egan, K.M., Eilber, U., Einbeigi, Z., Ejlertsen, B., Ellis, S., Frost, D., Lalloo, F., Fasching, P.A., Figueroa, J.D., Flyger, H., Friedlander, M., Friedman, E., Gambino, G., Gao, Y.T., Garber, J., Garcia-Closas, M., Gehrig, A., Damiola, F., Lesueur, F., Mazoyer, S., Stoppa-Lyonnet, D., Giles, G.G., Godwin, A.K., Goldgar, D.E., González-Neira, A., Greene, M.H., Guenel, P., Haeberle, L., Haiman, C.A., Hallberg, E., Hamann, U., Hansen, T.V.O., Hart, S., Hartikainen, J.M., Hartman, M., Hassan, N., Healey, S., Hogervorst, F.B.L., Verhoef, S., Hendricks, C.B., Hillemanns, P., Hollestelle, A., Hulick, P.J., Hunter, D.J., Imyanitov, E.N., Isaacs, C., Ito, H., Jakubowska, A., Janavicius, R., Jaworska-Bieniek, K., Jensen, U.B., John, E.M., Beauparlant, C.J., Jones, M., Kabisch, M., Kang, D., Karlan, B.Y., Kauppila, S., Kerin, M.J., Khan, S., Khusnutdinova, E., Knight, J.A., Konstantopoulou, I., Kraft, P., Kwong, A., Laitman, Y., Lambrechts, D., Lazaro, C., Le Marchand, L., Lee, C.N., Lee, M.H., Lester, J., Li, J., Liljegren, A., Lindblom, A., Lophatananon, A., Lubinski, J., Mai, P.L., Mannermaa, A., Manoukian, S., Margolin, S., Marme, F., Matsuo, K., McGuffog, L., Meindl, A., Menegaux, F., Montagna, M., Muir, K., Mulligan, A.M., Nathanson, K.L., Neuhausen, S.L., Nevanlinna, H., Newcomb, P.A., Nord, S., Nussbaum, R.L., Offit, K., Olah, E., Olopade, O.I., Olswold, C., Osorio, A., Papi, L., Park-Simon, T.W., Paulsson-Karlsson. Y., Peeters, S., Peissel, B., Peterlongo, P., Peto, J., Pfeiler, G., Phelan, C.M., Presneau, Nadège, Presneau, N., Radice, P., Rahman, N., Ramus, S.J., Rashid, M.U., Rennert, G., Rhiem, K., Rudolph, A., Salani, R., Sangrajrang, S., Sawyer, E.J., Schmidt, M.K., Schmutzler, R.K., Schoemaker, M.J., Schürmann, P., Seynaeve, C., Shen, C.Y., Shrubsole, M.J., Shu, X.O., Sigurdson, A., Singer, C.F., Slager, S., Soucy, P., Southey, M., Steinemann, D., Swerdlow, A., Szabo, C.I., Tchatchou, S., Teixeira, M.R., Teo, S.H., Terry, M.B., Tessier, D.C., Teulé, A., Thomassen, M., Tihomirova, L., Tischkowitz, M., Toland, A.E., Tung, N., Turnbull, C., van den Ouweland, A.M., van Rensburg, E.J., Ven den Berg, D., Vijai, J., Wang-Gohrke, S., Weitzel, J.N., Whittemore, A.S., Winqvist, R., Wong, T.Y., Wu, A.H., Yannoukakos, D., Yu, J.C., Pharoah, P.D., Hall, P., Chenevix-Trench, G., Dunning, A.M., Simard, J., Couch, F.J., Antoniou, A.C., Easton, D.F., Zheng, W., Zeng, C., Guo, X., Long, J., Kuchenbaecker, K.B., Droit, A., Michailidou, K., Ghoussaini, M., Kar, S., Freeman, A., Hopper, J.L., Milne, R.L., Bolla, M.K., Wang, Q., Dennis, J., Agata, S., Ahmed, S., Aittomaki, K., Andrulis, I.L., Anton-Culver, H., Antonenkova, N.N., Arason, A., Arndt, V., Arun, B.K., Arver, B., Bacot, F., Barrowdale, D., Baynes, C., Beeghly-Fadiel, A., Benitez, J., Bermisheva, M., Blomqvist, C., Blot, W.J., Bogdanova, N.V., Bojesen, S.E., Bonanni, B., Borresen-Dale, A.-L., Brand, J.S., Brauch, H., Brennan, P., Brenner, H., Broeks, A., Brüning, T., Burwinkel, B., Buys, S.S., Cai, Q., Caldes, T., Campbell, I., Carpenter, J., Chang-Claude, J., Choi, J.Y., Claes, K.B.M., Clarke, C., Cox, A., Cross, S.S., Czene, K., Daly, M.B., de la Hoya, M., De Leeneer, K., Devilee, P., Diez, O., Domchek, S.M., Doody, M.M., Dorfling, C.M., Dörk, T., Dos Santos Silva, I., Dumont, M., Dwek, M., Dworniczak, B., Egan, K.M., Eilber, U., Einbeigi, Z., Ejlertsen, B., Ellis, S., Frost, D., Lalloo, F., Fasching, P.A., Figueroa, J.D., Flyger, H., Friedlander, M., Friedman, E., Gambino, G., Gao, Y.T., Garber, J., Garcia-Closas, M., Gehrig, A., Damiola, F., Lesueur, F., Mazoyer, S., Stoppa-Lyonnet, D., Giles, G.G., Godwin, A.K., Goldgar, D.E., González-Neira, A., Greene, M.H., Guenel, P., Haeberle, L., Haiman, C.A., Hallberg, E., Hamann, U., Hansen, T.V.O., Hart, S., Hartikainen, J.M., Hartman, M., Hassan, N., Healey, S., Hogervorst, F.B.L., Verhoef, S., Hendricks, C.B., Hillemanns, P., Hollestelle, A., Hulick, P.J., Hunter, D.J., Imyanitov, E.N., Isaacs, C., Ito, H., Jakubowska, A., Janavicius, R., Jaworska-Bieniek, K., Jensen, U.B., John, E.M., Beauparlant, C.J., Jones, M., Kabisch, M., Kang, D., Karlan, B.Y., Kauppila, S., Kerin, M.J., Khan, S., Khusnutdinova, E., Knight, J.A., Konstantopoulou, I., Kraft, P., Kwong, A., Laitman, Y., Lambrechts, D., Lazaro, C., Le Marchand, L., Lee, C.N., Lee, M.H., Lester, J., Li, J., Liljegren, A., Lindblom, A., Lophatananon, A., Lubinski, J., Mai, P.L., Mannermaa, A., Manoukian, S., Margolin, S., Marme, F., Matsuo, K., McGuffog, L., Meindl, A., Menegaux, F., Montagna, M., Muir, K., Mulligan, A.M., Nathanson, K.L., Neuhausen, S.L., Nevanlinna, H., Newcomb, P.A., Nord, S., Nussbaum, R.L., Offit, K., Olah, E., Olopade, O.I., Olswold, C., Osorio, A., Papi, L., Park-Simon, T.W., Paulsson-Karlsson. Y., Peeters, S., Peissel, B., Peterlongo, P., Peto, J., Pfeiler, G., Phelan, C.M., Presneau, Nadège, Presneau, N., Radice, P., Rahman, N., Ramus, S.J., Rashid, M.U., Rennert, G., Rhiem, K., Rudolph, A., Salani, R., Sangrajrang, S., Sawyer, E.J., Schmidt, M.K., Schmutzler, R.K., Schoemaker, M.J., Schürmann, P., Seynaeve, C., Shen, C.Y., Shrubsole, M.J., Shu, X.O., Sigurdson, A., Singer, C.F., Slager, S., Soucy, P., Southey, M., Steinemann, D., Swerdlow, A., Szabo, C.I., Tchatchou, S., Teixeira, M.R., Teo, S.H., Terry, M.B., Tessier, D.C., Teulé, A., Thomassen, M., Tihomirova, L., Tischkowitz, M., Toland, A.E., Tung, N., Turnbull, C., van den Ouweland, A.M., van Rensburg, E.J., Ven den Berg, D., Vijai, J., Wang-Gohrke, S., Weitzel, J.N., Whittemore, A.S., Winqvist, R., Wong, T.Y., Wu, A.H., Yannoukakos, D., Yu, J.C., Pharoah, P.D., Hall, P., Chenevix-Trench, G., Dunning, A.M., Simard, J., Couch, F.J., Antoniou, A.C., Easton, D.F., and Zheng, W.
Abstract: BACKGROUND: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. METHOD: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/ ), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. RESULTS: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 × 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 × 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 × 10(-4)) identified in the general populations, and rs113824616 (P = 7 × 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05. CONCLUSION: This
Published: 2016

49. Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer

Author: Couch, F.J. (Fergus), Kuchenbaecker, K.B. (Karoline), Michailidou, K. (Kyriaki), Mendoza-Fandino, G.A. (Gustavo A.), Nord, S. (Silje), Lilyquist, J. (Janna), Olswold, C. (Curtis), Hallberg, B. (Boubou), Agata, S. (Simona), Ahsan, H. (Habibul), Aittomäki, K. (Kristiina), Ambrosone, C.B. (Christine), Andrulis, I.L. (Irene), Anton-Culver, H. (Hoda), Arndt, V. (Volker), Arun, B.K. (Banu), Arver, B. (Brita Wasteson), Barile, M. (Monica), Barkardottir, R.B. (Rosa), Barrowdale, D. (Daniel), Beckmann, L. (Lars), Beckmann, M.W. (Matthias), Benítez, J. (Javier), Blank, S.V. (Stephanie), Blomqvist, C. (Carl), Bogdanova, N.V. (Natalia), Bojesen, S.E. (Stig), Bolla, M.K. (Manjeet), Bonnani, B. (Bernardo), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Burwinkel, B. (Barbara), Buys, S.S. (Saundra S.), Caldes, T. (Trinidad), Caligo, M.A. (Maria), Canzian, F. (Federico), Carpenter, T.A. (Adrian), Chang-Claude, J. (Jenny), Chanock, S.J. (Stephen J.), Chung, W.K. (Wendy K.), Claes, K.B.M. (Kathleen B.M.), Cox, A. (Angela), Cross, S.S. (Simon), Cunningham, J.M. (Julie), Czene, K. (Kamila), Daly, M.B. (Mary B.), Damiola, F. (Francesca), Darabi, H. (Hatef), Hoya, M. (Miguel) de La, Devilee, P. (Peter), Díez, O. (Orland), Ding, Y.C. (Yuan), Dolcetti, R. (Riccardo), Domchek, S.M. (Susan), Dorfling, C.M. (Cecilia), Santos Silva, I. (Isabel) dos, Dumont, M. (Martine), Dunning, A.M. (Alison), Eccles, D. (Diana), Ehrencrona, H. (Hans), Ekici, A.B. (Arif), Eliassen, H. (Heather), Ellis, S.D. (Steve), Fasching, P.A. (Peter), Figueroa, J.D. (Jonine), Flesch-Janys, D. (Dieter), Försti, A. (Asta), Fostira, F. (Florentia), Foulkes, W.D. (William), Friebel, M.O.W. (Mark ), Friedman, E. (Eitan), Frost, D. (Debra), Gabrielson, M. (Marike), Gammon, M. (Marilie), Ganz, P.A. (Patricia A.), Gapstur, S.M. (Susan M.), Garber, J. (Judy), Gaudet, M.M. (Mia), Gayther, S.A. (Simon), Gerdes, A-M. (Anne-Marie), Ghoussaini, M. (Maya), Giles, G.G. (Graham), Glendon, G. (Gord), Godwin, A.K. (Andrew K.), Goldberg, M.S. (Mark), Goldgar, D. (David), González-Neira, A. (Anna), Greene, M.H. (Mark H.), Gronwald, J. (Jacek), Guénel, P. (Pascal), Gunter, M.J. (Marc J.), Haeberle, L. (Lothar), Haiman, C.A. (Christopher A.), Hamann, U. (Ute), Hansen, T.V.O. (Thomas), Hart, S. (Stewart), Healey, S. (Sue), Heikkinen, T. (Tuomas), Henderson, B.E. (Brian), Herzog, J. (Josef), Hogervorst, F.B.L. (Frans), Hollestelle, A. (Antoinette), Hooning, M.J. (Maartje), Hoover, R.N. (Robert), Hopper, J.L. (John), Humphreys, K. (Keith), Hunter, D. (David), Huzarski, T. (Tomasz), Imyanitov, E.N. (Evgeny N.), Isaacs, C. (Claudine), Jakubowska, A. (Anna), James, M. (Margaret), Janavicius, R. (Ramunas), Jensen, U.B., John, E.M. (Esther), Jones, M. (Michael), Kabisch, M. (Maria), Kar, S. (Siddhartha), Karlan, B.Y. (Beth Y.), Khan, S. (Sofia), Khaw, K.T., Kibriya, M.G. (Muhammad), Knight, J.A. (Julia), Ko, Y.-D. (Yon-Dschun), Konstantopoulou, I. (I.), Kosma, V-M. (Veli-Matti), Kristensen, V. (Vessela), Kwong, A. (Ava), Laitman, Y. (Yael), Lambrechts, D. (Diether), Lázaro, C. (Conxi), Lee, E. (Eunjung), Le Marchand, L. (Loic), Lester, K.J. (Kathryn), Lindblom, A. (Annika), Lindor, N.M. (Noralane), Lindstrom, S. (Stephen), Liu, J. (Jianjun), Long, J. (Jirong), Lubinski, J. (Jan), Mai, P.L. (Phuong), Makalic, E. (Enes), Malone, K.E. (Kathleen E.), Mannermaa, A. (Arto), Manoukian, S. (Siranoush), Margolin, S. (Sara), Marme, F. (Federick), Martens, J.W.M. (John), McGuffog, L. (Lesley), Meindl, A. (Alfons), Miller, A. (Austin), Milne, R.L. (Roger), Miron, P. (Penelope), Montagna, M. (Marco), Mazoyer, S. (Sylvie), Mulligan, A.-M. (Anna-Marie), Muranen, T.A. (Taru), Nathanson, K.L. (Katherine), Neuhausen, S.L. (Susan), Nevanlinna, H. (Heli), Nordestgaard, B.G. (Børge), Nussbaum, R. (Robert), Offit, K. (Kenneth), Olah, E., Olopade, O.I. (Olufunmilayo I.), Olson, J.E. (Janet), Osorio, A. (Ana), Park, S.K. (Sue K.), Peeters, P.H.M., Peissel, B. (Bernard), Peterlongo, P. (Paolo), Peto, J. (Julian), Phelan, C. (Catherine), Pilarski, R. (Robert), Poppe, B. (Bruce), Pykäs, K. (Katri), Radice, P. (Paolo), Rahman, N. (Nazneen), Rantala, J. (Johanna), Rappaport, C. (Christine), Rennert, G. (Gad), Richardson, A.L. (Andrea), Robson, M. (Mark), Romieu, I. (Isabelle), Rudolph, A. (Anja), Rutgers, E.J.T. (Emiel), Sanchez, M.-J. (Maria-Jose), Santella, R. (Regina), Sawyer, E.J. (Elinor), Schmidt, D.F. (Daniel), Schmidt, M.K. (Marjanka), Schmutzler, R.K. (Rita), Schumacher, F.R. (Fredrick), Scott, R.J. (Rodney), Senter, L. (Leigha), Sharma, P. (Priyanka), Simard, J. (Jacques), Singer, C.F. (Christian), Sinilnikova, O. (Olga), Soucy, P. (Penny), Southey, M.C. (Melissa), Steinemann, D. (Doris), Stenmark-Askmalm, M. (Marie), Stoppa-Lyonnet, D. (Dominique), Swerdlow, A.J. (Anthony ), Szabo, C. (Csilla), Tamimi, R. (Rulla), Tapper, W. (William), Teixeira, P.J., Teo, S.-H. (Soo-Hwang), Terry, M.B. (Mary Beth), Thomassen, M. (Mads), Thompson, D. (Deborah), Tihomirova, L. (Laima), Toland, A.E. (Amanda), Tollenaar, R.A.E.M. (Rob), Tomlinson, I.P. (Ian), Truong, T. (Thérèse), Tsimiklis, H. (Helen), Teulé, A. (A.), Tumino, R. (Rosario), Tung, N. (Nadine), Turnbull, C. (Clare), Ursin, G. (Giski), Deurzen, C.H.M. (Carolien) van, Rensburg, E.J. (Elizabeth) van, Varon-Mateeva, R. (Raymonda), Wang, Z. (Zhaoming), Wang-Gohrke, S. (Shan), Weiderpass, E. (Elisabete), Weitzel, J.N. (Jeffrey), Whittemore, A.S. (Alice S.), Wildiers, H. (Hans), Winqvist, R. (Robert), Yang, X.R. (Xiaohong R.), Yannoukakos, D. (Drakoulis), Yao, S. (Song), Zamora, M.P. (Pilar), Zheng, W. (Wei), Hall, P. (Per), Kraft, P. (Peter), Vachon, C. (Celine), Slager, S. (Susan), Chenevix-Trench, G. (Georgia), Pharoah, P.D.P. (Paul), Monteiro, A.A.N. (Alvaro A. N.), García-Closas, M. (Montserrat), Easton, D.F. (Douglas F.), Antoniou, A.C. (Antonis), Couch, F.J. (Fergus), Kuchenbaecker, K.B. (Karoline), Michailidou, K. (Kyriaki), Mendoza-Fandino, G.A. (Gustavo A.), Nord, S. (Silje), Lilyquist, J. (Janna), Olswold, C. (Curtis), Hallberg, B. (Boubou), Agata, S. (Simona), Ahsan, H. (Habibul), Aittomäki, K. (Kristiina), Ambrosone, C.B. (Christine), Andrulis, I.L. (Irene), Anton-Culver, H. (Hoda), Arndt, V. (Volker), Arun, B.K. (Banu), Arver, B. (Brita Wasteson), Barile, M. (Monica), Barkardottir, R.B. (Rosa), Barrowdale, D. (Daniel), Beckmann, L. (Lars), Beckmann, M.W. (Matthias), Benítez, J. (Javier), Blank, S.V. (Stephanie), Blomqvist, C. (Carl), Bogdanova, N.V. (Natalia), Bojesen, S.E. (Stig), Bolla, M.K. (Manjeet), Bonnani, B. (Bernardo), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Burwinkel, B. (Barbara), Buys, S.S. (Saundra S.), Caldes, T. (Trinidad), Caligo, M.A. (Maria), Canzian, F. (Federico), Carpenter, T.A. (Adrian), Chang-Claude, J. (Jenny), Chanock, S.J. (Stephen J.), Chung, W.K. (Wendy K.), Claes, K.B.M. (Kathleen B.M.), Cox, A. (Angela), Cross, S.S. (Simon), Cunningham, J.M. (Julie), Czene, K. (Kamila), Daly, M.B. (Mary B.), Damiola, F. (Francesca), Darabi, H. (Hatef), Hoya, M. (Miguel) de La, Devilee, P. (Peter), Díez, O. (Orland), Ding, Y.C. (Yuan), Dolcetti, R. (Riccardo), Domchek, S.M. (Susan), Dorfling, C.M. (Cecilia), Santos Silva, I. (Isabel) dos, Dumont, M. (Martine), Dunning, A.M. (Alison), Eccles, D. (Diana), Ehrencrona, H. (Hans), Ekici, A.B. (Arif), Eliassen, H. (Heather), Ellis, S.D. (Steve), Fasching, P.A. (Peter), Figueroa, J.D. (Jonine), Flesch-Janys, D. (Dieter), Försti, A. (Asta), Fostira, F. (Florentia), Foulkes, W.D. (William), Friebel, M.O.W. (Mark ), Friedman, E. (Eitan), Frost, D. (Debra), Gabrielson, M. (Marike), Gammon, M. (Marilie), Ganz, P.A. (Patricia A.), Gapstur, S.M. (Susan M.), Garber, J. (Judy), Gaudet, M.M. (Mia), Gayther, S.A. (Simon), Gerdes, A-M. (Anne-Marie), Ghoussaini, M. (Maya), Giles, G.G. (Graham), Glendon, G. (Gord), Godwin, A.K. (Andrew K.), Goldberg, M.S. (Mark), Goldgar, D. (David), González-Neira, A. (Anna), Greene, M.H. (Mark H.), Gronwald, J. (Jacek), Guénel, P. (Pascal), Gunter, M.J. (Marc J.), Haeberle, L. (Lothar), Haiman, C.A. (Christopher A.), Hamann, U. (Ute), Hansen, T.V.O. (Thomas), Hart, S. (Stewart), Healey, S. (Sue), Heikkinen, T. (Tuomas), Henderson, B.E. (Brian), Herzog, J. (Josef), Hogervorst, F.B.L. (Frans), Hollestelle, A. (Antoinette), Hooning, M.J. (Maartje), Hoover, R.N. (Robert), Hopper, J.L. (John), Humphreys, K. (Keith), Hunter, D. (David), Huzarski, T. (Tomasz), Imyanitov, E.N. (Evgeny N.), Isaacs, C. (Claudine), Jakubowska, A. (Anna), James, M. (Margaret), Janavicius, R. (Ramunas), Jensen, U.B., John, E.M. (Esther), Jones, M. (Michael), Kabisch, M. (Maria), Kar, S. (Siddhartha), Karlan, B.Y. (Beth Y.), Khan, S. (Sofia), Khaw, K.T., Kibriya, M.G. (Muhammad), Knight, J.A. (Julia), Ko, Y.-D. (Yon-Dschun), Konstantopoulou, I. (I.), Kosma, V-M. (Veli-Matti), Kristensen, V. (Vessela), Kwong, A. (Ava), Laitman, Y. (Yael), Lambrechts, D. (Diether), Lázaro, C. (Conxi), Lee, E. (Eunjung), Le Marchand, L. (Loic), Lester, K.J. (Kathryn), Lindblom, A. (Annika), Lindor, N.M. (Noralane), Lindstrom, S. (Stephen), Liu, J. (Jianjun), Long, J. (Jirong), Lubinski, J. (Jan), Mai, P.L. (Phuong), Makalic, E. (Enes), Malone, K.E. (Kathleen E.), Mannermaa, A. (Arto), Manoukian, S. (Siranoush), Margolin, S. (Sara), Marme, F. (Federick), Martens, J.W.M. (John), McGuffog, L. (Lesley), Meindl, A. (Alfons), Miller, A. (Austin), Milne, R.L. (Roger), Miron, P. (Penelope), Montagna, M. (Marco), Mazoyer, S. (Sylvie), Mulligan, A.-M. (Anna-Marie), Muranen, T.A. (Taru), Nathanson, K.L. (Katherine), Neuhausen, S.L. (Susan), Nevanlinna, H. (Heli), Nordestgaard, B.G. (Børge), Nussbaum, R. (Robert), Offit, K. (Kenneth), Olah, E., Olopade, O.I. (Olufunmilayo I.), Olson, J.E. (Janet), Osorio, A. (Ana), Park, S.K. (Sue K.), Peeters, P.H.M., Peissel, B. (Bernard), Peterlongo, P. (Paolo), Peto, J. (Julian), Phelan, C. (Catherine), Pilarski, R. (Robert), Poppe, B. (Bruce), Pykäs, K. (Katri), Radice, P. (Paolo), Rahman, N. (Nazneen), Rantala, J. (Johanna), Rappaport, C. (Christine), Rennert, G. (Gad), Richardson, A.L. (Andrea), Robson, M. (Mark), Romieu, I. (Isabelle), Rudolph, A. (Anja), Rutgers, E.J.T. (Emiel), Sanchez, M.-J. (Maria-Jose), Santella, R. (Regina), Sawyer, E.J. (Elinor), Schmidt, D.F. (Daniel), Schmidt, M.K. (Marjanka), Schmutzler, R.K. (Rita), Schumacher, F.R. (Fredrick), Scott, R.J. (Rodney), Senter, L. (Leigha), Sharma, P. (Priyanka), Simard, J. (Jacques), Singer, C.F. (Christian), Sinilnikova, O. (Olga), Soucy, P. (Penny), Southey, M.C. (Melissa), Steinemann, D. (Doris), Stenmark-Askmalm, M. (Marie), Stoppa-Lyonnet, D. (Dominique), Swerdlow, A.J. (Anthony ), Szabo, C. (Csilla), Tamimi, R. (Rulla), Tapper, W. (William), Teixeira, P.J., Teo, S.-H. (Soo-Hwang), Terry, M.B. (Mary Beth), Thomassen, M. (Mads), Thompson, D. (Deborah), Tihomirova, L. (Laima), Toland, A.E. (Amanda), Tollenaar, R.A.E.M. (Rob), Tomlinson, I.P. (Ian), Truong, T. (Thérèse), Tsimiklis, H. (Helen), Teulé, A. (A.), Tumino, R. (Rosario), Tung, N. (Nadine), Turnbull, C. (Clare), Ursin, G. (Giski), Deurzen, C.H.M. (Carolien) van, Rensburg, E.J. (Elizabeth) van, Varon-Mateeva, R. (Raymonda), Wang, Z. (Zhaoming), Wang-Gohrke, S. (Shan), Weiderpass, E. (Elisabete), Weitzel, J.N. (Jeffrey), Whittemore, A.S. (Alice S.), Wildiers, H. (Hans), Winqvist, R. (Robert), Yang, X.R. (Xiaohong R.), Yannoukakos, D. (Drakoulis), Yao, S. (Song), Zamora, M.P. (Pilar), Zheng, W. (Wei), Hall, P. (Per), Kraft, P. (Peter), Vachon, C. (Celine), Slager, S. (Susan), Chenevix-Trench, G. (Georgia), Pharoah, P.D.P. (Paul), Monteiro, A.A.N. (Alvaro A. N.), García-Closas, M. (Montserrat), Easton, D.F. (Douglas F.), and Antoniou, A.C. (Antonis)
Abstract: Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 × 10-8) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negati
Published: 2016
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50. No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer

Author: Hollestelle, A. (Antoinette), Baan, F.H. (Frederieke) van der, Berchuck, A. (Andrew), Johnatty, S.E. (Sharon), Aben, K.K.H. (Katja), Agnarsson, B.A. (Bjarni), Aittomäki, K. (Kristiina), Alducci, E. (Elisa), Andrulis, I.L. (Irene), Anton-Culver, H. (Hoda), Antonenkova, N.N. (Natalia), Antoniou, A.C. (Antonis), Apicella, C. (Carmel), Arndt, V. (Volker), Arnold, N. (Norbert), Arun, B.K. (Banu), Arver, B. (Brita Wasteson), Ashworth, A. (Alan), Baglietto, L. (Laura), Balleine, R. (Rosemary), Bandera, E.V. (Elisa), Barrowdale, D. (Daniel), Bean, Y.T. (Yukie), Beckmann, L. (Lars), Beckmann, M.W. (Matthias), Benítez, J. (Javier), Berger, A. (Andreas), Berger, R. (Raanan), Beuselinck, B. (B.), Bisogna, M. (Maria), Bjorge, L. (Line), Blomqvist, C. (Carl), Bogdanova, N.V. (Natalia), Bojesen, A. (Anders), Bojesen, S.E. (Stig), Bolla, M.K. (Manjeet), Bonnani, B. (Bernardo), Brand, J.S. (Judith S.), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Brinton, L.A. (Louise), Brooks-Wilson, A. (Angela), Bruinsma, F. (Fiona), Brunet, J. (Joan), Brüning, T. (Thomas), Budzilowska, A. (Agnieszka), Bunker, C.H. (Clareann H.), Burwinkel, B. (Barbara), Butzow, R. (Ralf), Buys, S.S. (Saundra S.), Caligo, M.A. (Maria), Campbell, I. (Ian), Carter, J. (Jonathan), Chang-Claude, J. (Jenny), Chanock, S.J. (Stephen J.), Claes, K.B.M. (Kathleen B.M.), Collée, J.M. (Margriet), Cook, L.S. (Linda S.), Couch, F.J. (Fergus), Cox, A. (Angela), Cramer, D.W. (Daniel), Cross, S.S. (Simon), Cunningham, J.M. (Julie), Cybulski, C. (Cezary), Czene, K. (Kamila), Damiola, F. (Francesca), Dansonka-Mieszkowska, A. (Agnieszka), Darabi, H. (Hatef), Hoya, M. (Miguel) de La, DeFazio, A. (Anna), Dennis, J. (Joe), Devilee, P. (Peter), Dicks, E. (Ed), Díez, O. (Orland), Doherty, J.A. (Jennifer A.), Domchek, S.M. (Susan), Dorfling, C.M. (Cecilia), Dörk, T. (Thilo), Santos Silva, I. (Isabel) dos, Du Bois, A. (Andreas), Dumont, M. (Martine), Dunning, A.M. (Alison), Duran, M. (Mercedes), Easton, D.F. (Douglas F.), Eccles, D. (Diana), Edwards, R. (Robert), Ehrencrona, H. (Hans), Ejlertsen, B. (Bent), Ekici, A.B. (Arif), Ellis, S.D. (Steve), Engel, C. (Christoph), Eriksson, M. (Mikael), Fasching, P.A. (Peter), Feliubadaló, L. (L.), Figueroa, J.D. (Jonine), Flesch-Janys, D. (Dieter), Fletcher, O. (Olivia), Fontaine, A. (Annette), Fortuzzi, S. (S.), Fostira, F. (Florentia), Fridley, B.L. (Brooke), Friebel, M.O.W. (Mark ), Friedman, E. (Eitan), Friel, G. (Grace), Frost, D. (Debra), Garber, J. (Judy), García-Closas, M. (Montserrat), Gayther, S.A. (Simon), Gentry-Maharaj, A. (Aleksandra), Gerdes, A-M. (Anne-Marie), Giles, G.G. (Graham), Glasspool, R. (Rosalind), Glendon, G. (Gord), Godwin, A.K. (Andrew K.), Goodman, M.T. (Marc T.), Gore, M. (Martin), Greene, M.H. (Mark H.), Grip, M. (Mervi), Gronwald, J. (Jacek), Gschwantler-Kaulich, D. (Daphne), Guénel, P. (Pascal), Guzman, S.R. (Starr R.), Haeberle, L. (Lothar), Haiman, C.A. (Christopher A.), Hall, P. (Per), Halverson, S.L. (Sandra L.), Hamann, U. (Ute), Hansen, T.V.O. (Thomas), Harter, P. (Philipp), Hartikainen, J.M. (J.), Healey, S. (Sue), Hein, R. (Rebecca), Heitz, P.U., Henderson, B.E. (Brian), Herzog, J. (Josef), Hildebrandt, M.A.T. (Michelle), Høgdall, C.K. (Claus), Høgdall, E. (Estrid), Hogervorst, F.B.L. (Frans), Hopper, J.L. (John), Humphreys, K. (Keith), Huzarski, T. (Tomasz), Imyanitov, E.N. (Evgeny N.), Isaacs, C. (Claudine), Jakubowska, A. (Anna), Janavicius, R. (Ramunas), Jaworska, K. (Katarzyna), Jensen, A. (Allan), Jensen, U.B., Johnson, N. (Nichola), Jukkola-Vuorinen, A. (Arja), Kabisch, M. (Maria), Karlan, B.Y. (Beth Y.), Kataja, V. (Vesa), Kauff, N. (Noah), Kelemen, L.E. (Linda), Kerin, M. (Michael), Kiemeney, L.A.L.M. (Bart), Kjaer, M. (Michael), Knight, J.A. (Julia), Knol-Bout, J.P. (Jacoba P.), Konstantopoulou, I. (I.), Kosma, V-M. (Veli-Matti), Krakstad, C. (Camilla), Kristensen, V. (Vessela), Kuchenbaecker, K.B. (Karoline), Kupryjanczyk, J. (Jolanta), Laitman, Y. (Yael), Lambrechts, D. (Diether), Lambrechts, S. (Sandrina), Larson, M.C. (Melissa), Lasa, A. (Adriana), Laurent-Puig, P. (Pierre), Lázaro, C. (Conxi), Le, N. (Nhu), Le Marchand, L. (Loic), Leminen, A. (Arto), Lester, K.J. (Kathryn), Levine, D.A. (Douglas), Li, J. (Jingmei), Liang, D. (Dong), Lindblom, A. (Annika), Lindor, N.M. (Noralane), Lissowska, J. (Jolanta), Long, J. (Jirong), Lu, K.H. (Karen), Lubinski, J. (Jan), Lundvall, L. (Lene), Lurie, G. (Galina), Mai, P.L. (Phuong), Mannermaa, A. (Arto), Margolin, S. (Sara), Mariette, F. (F.), Marme, F. (Federick), Martens, J.W.M. (John), Massuger, L.F. (Leon), Maugard, C., Mazoyer, S. (Sylvie), McGuffog, L. (Lesley), McGuire, W.P., McLean, C.A. (Catriona Ann), McNeish, I. (Iain), Meindl, A. (Alfons), Menegaux, F. (Florence), Menéndez, P. (Primitiva), Menkiszak, J. (Janusz), Menon, U. (Usha), Mensenkamp, A.R. (Arjen), Miller, N. (Nicola), Milne, R.L. (Roger), Modugno, F. (Francesmary), Montagna, M. (Marco), Moysich, K.B. (Kirsten B.), Müller, H. (Heiko), Mulligan, A.-M. (Anna-Marie), Muranen, T.A. (Taru), Narod, S.A. (Steven A.), Nathanson, K.L. (Katherine), Ness, R.B. (Roberta B.), Neuhausen, S.L. (Susan), Nevanlinna, H. (Heli), Neven, P. (Patrick), Nielsen, F. (Finn), Nielsen, S.F. (Sune), Nordestgaard, B.G. (Børge), Nussbaum, R. (Robert), Odunsi, K. (Kunle), Offit, K. (Kenneth), Olah, E., Olopade, O.I. (Olufunmilayo I.), Olson, J.E. (Janet), Olson, S.H. (Sara), Oosterwijk, J.C. (Jan), Orlow, I. (Irene), Orr, N. (Nick), Orsulic, S. (Sandra), Osorio, A. (Ana), Ottini, L. (Laura), Paul, J. (James), Pearce, C.L. (Celeste), Pedersen, I.S. (Inge Sokilde), Peissel, B. (Bernard), Pejovic, T. (Tanja), Pelttari, L.M. (Liisa), Perkins, J. (Jo), Permuth-Wey, J. (Jenny), Peterlongo, P. (Paolo), Peto, J. (Julian), Phelan, C. (Catherine), Phillips, K.-A. (Kelly-Anne), Piedmonte, M. (Marion), Pike, M.C. (Malcolm C.), Platte, R. (Radka), Plisiecka-Halasa, J. (Joanna), Poole, E.M. (Elizabeth), Poppe, B. (Bruce), Pykäs, K. (Katri), Radice, P. (Paolo), Ramus, S.J. (Susan), Rebbeck, R. (Timothy), Reed, M.W.R. (Malcolm W.R.), Rennert, G. (Gad), Risch, H. (Harvey), Robson, M. (Mark), Rodriguez, G. (Gustavo), Romero, A. (Atocha), Rossing, M.A. (Mary Anne), Rothstein, J.H. (Joseph H.), Rudolph, A. (Anja), Runnebaum, I.B. (Ingo), Salani, R. (Ritu), Salvesen, H.B. (Helga), Sawyer, E.J. (Elinor), Schildkraut, J.M. (Joellen), Schmidt, M.K. (Marjanka), Schmutzler, R.K. (Rita), Schneeweiss, A. (Andreas), Schoemaker, M. (Minouk), Schrauder, A. (André), Schumacher, F.R. (Fredrick), Schwaab, I. (Ira), Scuvera, G. (Giulietta), Sellers, T.A. (Thomas A.), Severi, G. (Gianluca), Seynaeve, C.M. (Caroline), Shah, M. (Mitul), Shrubsole, M. (Martha), Siddiqui, N. (Nadeem), Sieh, W. (Weiva), Simard, J. (Jacques), Singer, C.F. (Christian), Sinilnikova, O. (Olga), Smeets, D. (Dominiek), Sohn, C. (Christof), Soller, M. (Maria), Song, H. (Honglin), Soucy, P. (Penny), Southey, M.C. (Melissa), Stegmaier, C. (Christa), Stoppa-Lyonnet, D. (Dominique), Sucheston, L. (Lara), Swerdlow, A.J. (Anthony ), Tangen, I.L. (Ingvild L.), Tea, M.-K., Teixeira, P.J., Terry, K.L. (Kathryn), Terry, M.B. (Mary Beth), Thomassen, M. (Mads), Thompson, P.J. (Pamela J.), Tihomirova, L. (Laima), Tischkowitz, M. (Marc), Toland, A.E. (Amanda), Tollenaar, R.A.E.M. (Rob), Tomlinson, I. (Ian), Torres, D. (Diana), Truong, T. (Thérèse), Tsimiklis, H. (Helen), Tung, N. (Nadine), Tworoger, S. (Shelley), Tyrer, J.P. (Jonathan), Vachon, C. (Celine), Veer, L.J. (Laura) van 't, Altena, A.M. (Anne) van, Asperen, C.J. (Christi) van, Van Den Berg, D. (David), Ouweland, A.M.W. (Ans) van den, Doorn, H.C. (Lena) van, Van Nieuwenhuysen, E. (Els), Rensburg, E.J. (Elizabeth) van, Vergote, I. (Ignace), Verhoef, S., Vierkant, R.A. (Robert), Vijai, J. (Joseph), Vitonis, A.F. (Allison), Wachenfeldt, A. (Anna) von, Walsh, C.S. (Christine), Wang, Q. (Qing), Wang-Gohrke, S. (Shan), Wapenschmidt, B. (Barbara), Weischer, M. (Maren), Weitzel, J.N. (Jeffrey), Weltens, C. (Caroline), Wentzensen, N. (N.), Whittemore, A.S. (Alice S.), Wilkens, L.R. (Lynne R.), Winqvist, R. (Robert), Wu, A.H. (Anna), Wu, X. (Xifeng), Yang, H.P. (Hannah P.), Zaffaroni, D. (Daniela), Zamora, M.P. (Pilar), Zheng, W. (Wei), Ziogas, A. (Argyrios), Chenevix-Trench, G. (Georgia), Pharoah, P.D.P. (Paul), Rookus, M.A. (Matti), Hooning, M.J. (Maartje), Goode, E.L. (Ellen L.), Breast Cancer Family Register, EMBRACE, GENICA Network, HEBON, SWE-BRCA, Hollestelle, A. (Antoinette), Baan, F.H. (Frederieke) van der, Berchuck, A. (Andrew), Johnatty, S.E. (Sharon), Aben, K.K.H. (Katja), Agnarsson, B.A. (Bjarni), Aittomäki, K. (Kristiina), Alducci, E. (Elisa), Andrulis, I.L. (Irene), Anton-Culver, H. (Hoda), Antonenkova, N.N. (Natalia), Antoniou, A.C. (Antonis), Apicella, C. (Carmel), Arndt, V. (Volker), Arnold, N. (Norbert), Arun, B.K. (Banu), Arver, B. (Brita Wasteson), Ashworth, A. (Alan), Baglietto, L. (Laura), Balleine, R. (Rosemary), Bandera, E.V. (Elisa), Barrowdale, D. (Daniel), Bean, Y.T. (Yukie), Beckmann, L. (Lars), Beckmann, M.W. (Matthias), Benítez, J. (Javier), Berger, A. (Andreas), Berger, R. (Raanan), Beuselinck, B. (B.), Bisogna, M. (Maria), Bjorge, L. (Line), Blomqvist, C. (Carl), Bogdanova, N.V. (Natalia), Bojesen, A. (Anders), Bojesen, S.E. (Stig), Bolla, M.K. (Manjeet), Bonnani, B. (Bernardo), Brand, J.S. (Judith S.), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Brinton, L.A. (Louise), Brooks-Wilson, A. (Angela), Bruinsma, F. (Fiona), Brunet, J. (Joan), Brüning, T. (Thomas), Budzilowska, A. (Agnieszka), Bunker, C.H. (Clareann H.), Burwinkel, B. (Barbara), Butzow, R. (Ralf), Buys, S.S. (Saundra S.), Caligo, M.A. (Maria), Campbell, I. (Ian), Carter, J. (Jonathan), Chang-Claude, J. (Jenny), Chanock, S.J. (Stephen J.), Claes, K.B.M. (Kathleen B.M.), Collée, J.M. (Margriet), Cook, L.S. (Linda S.), Couch, F.J. (Fergus), Cox, A. (Angela), Cramer, D.W. (Daniel), Cross, S.S. (Simon), Cunningham, J.M. (Julie), Cybulski, C. (Cezary), Czene, K. (Kamila), Damiola, F. (Francesca), Dansonka-Mieszkowska, A. (Agnieszka), Darabi, H. (Hatef), Hoya, M. (Miguel) de La, DeFazio, A. (Anna), Dennis, J. (Joe), Devilee, P. (Peter), Dicks, E. (Ed), Díez, O. (Orland), Doherty, J.A. (Jennifer A.), Domchek, S.M. (Susan), Dorfling, C.M. (Cecilia), Dörk, T. (Thilo), Santos Silva, I. (Isabel) dos, Du Bois, A. (Andreas), Dumont, M. (Martine), Dunning, A.M. (Alison), Duran, M. (Mercedes), Easton, D.F. (Douglas F.), Eccles, D. (Diana), Edwards, R. (Robert), Ehrencrona, H. (Hans), Ejlertsen, B. (Bent), Ekici, A.B. (Arif), Ellis, S.D. (Steve), Engel, C. (Christoph), Eriksson, M. (Mikael), Fasching, P.A. (Peter), Feliubadaló, L. (L.), Figueroa, J.D. (Jonine), Flesch-Janys, D. (Dieter), Fletcher, O. (Olivia), Fontaine, A. (Annette), Fortuzzi, S. (S.), Fostira, F. (Florentia), Fridley, B.L. (Brooke), Friebel, M.O.W. (Mark ), Friedman, E. (Eitan), Friel, G. (Grace), Frost, D. (Debra), Garber, J. (Judy), García-Closas, M. (Montserrat), Gayther, S.A. (Simon), Gentry-Maharaj, A. (Aleksandra), Gerdes, A-M. (Anne-Marie), Giles, G.G. (Graham), Glasspool, R. (Rosalind), Glendon, G. (Gord), Godwin, A.K. (Andrew K.), Goodman, M.T. (Marc T.), Gore, M. (Martin), Greene, M.H. (Mark H.), Grip, M. (Mervi), Gronwald, J. (Jacek), Gschwantler-Kaulich, D. (Daphne), Guénel, P. (Pascal), Guzman, S.R. (Starr R.), Haeberle, L. (Lothar), Haiman, C.A. (Christopher A.), Hall, P. (Per), Halverson, S.L. (Sandra L.), Hamann, U. (Ute), Hansen, T.V.O. (Thomas), Harter, P. (Philipp), Hartikainen, J.M. (J.), Healey, S. (Sue), Hein, R. (Rebecca), Heitz, P.U., Henderson, B.E. (Brian), Herzog, J. (Josef), Hildebrandt, M.A.T. (Michelle), Høgdall, C.K. (Claus), Høgdall, E. (Estrid), Hogervorst, F.B.L. (Frans), Hopper, J.L. (John), Humphreys, K. (Keith), Huzarski, T. (Tomasz), Imyanitov, E.N. (Evgeny N.), Isaacs, C. (Claudine), Jakubowska, A. (Anna), Janavicius, R. (Ramunas), Jaworska, K. (Katarzyna), Jensen, A. (Allan), Jensen, U.B., Johnson, N. (Nichola), Jukkola-Vuorinen, A. (Arja), Kabisch, M. (Maria), Karlan, B.Y. (Beth Y.), Kataja, V. (Vesa), Kauff, N. (Noah), Kelemen, L.E. (Linda), Kerin, M. (Michael), Kiemeney, L.A.L.M. (Bart), Kjaer, M. (Michael), Knight, J.A. (Julia), Knol-Bout, J.P. (Jacoba P.), Konstantopoulou, I. (I.), Kosma, V-M. (Veli-Matti), Krakstad, C. (Camilla), Kristensen, V. (Vessela), Kuchenbaecker, K.B. (Karoline), Kupryjanczyk, J. (Jolanta), Laitman, Y. (Yael), Lambrechts, D. (Diether), Lambrechts, S. (Sandrina), Larson, M.C. (Melissa), Lasa, A. (Adriana), Laurent-Puig, P. (Pierre), Lázaro, C. (Conxi), Le, N. (Nhu), Le Marchand, L. (Loic), Leminen, A. (Arto), Lester, K.J. (Kathryn), Levine, D.A. (Douglas), Li, J. (Jingmei), Liang, D. (Dong), Lindblom, A. (Annika), Lindor, N.M. (Noralane), Lissowska, J. (Jolanta), Long, J. (Jirong), Lu, K.H. (Karen), Lubinski, J. (Jan), Lundvall, L. (Lene), Lurie, G. (Galina), Mai, P.L. (Phuong), Mannermaa, A. (Arto), Margolin, S. (Sara), Mariette, F. (F.), Marme, F. (Federick), Martens, J.W.M. (John), Massuger, L.F. (Leon), Maugard, C., Mazoyer, S. (Sylvie), McGuffog, L. (Lesley), McGuire, W.P., McLean, C.A. (Catriona Ann), McNeish, I. (Iain), Meindl, A. (Alfons), Menegaux, F. (Florence), Menéndez, P. (Primitiva), Menkiszak, J. (Janusz), Menon, U. (Usha), Mensenkamp, A.R. (Arjen), Miller, N. (Nicola), Milne, R.L. (Roger), Modugno, F. (Francesmary), Montagna, M. (Marco), Moysich, K.B. (Kirsten B.), Müller, H. (Heiko), Mulligan, A.-M. (Anna-Marie), Muranen, T.A. (Taru), Narod, S.A. (Steven A.), Nathanson, K.L. (Katherine), Ness, R.B. (Roberta B.), Neuhausen, S.L. (Susan), Nevanlinna, H. (Heli), Neven, P. (Patrick), Nielsen, F. (Finn), Nielsen, S.F. (Sune), Nordestgaard, B.G. (Børge), Nussbaum, R. (Robert), Odunsi, K. (Kunle), Offit, K. (Kenneth), Olah, E., Olopade, O.I. (Olufunmilayo I.), Olson, J.E. (Janet), Olson, S.H. (Sara), Oosterwijk, J.C. (Jan), Orlow, I. (Irene), Orr, N. 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Abstract: Objective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and br
Published: 2016
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