981 results on '"Rennert, G"'
Search Results
2. Very High Mutation Rate in Offspring of Chernobyl Accident Liquidators
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Korol, A. B., Kirzhner, V. M., Avivi, A., Fahima, T., Nevo, Eviatar, Shapiro, S., Rennert, G., Piatak, O., Stepanova, E. I., and Skvarskaja, E.
- Published
- 2001
3. The role of CHADS2 and CHA2DS2‐VASc scores in the prediction of stroke in individuals without atrial fibrillation: a population‐based study
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Saliba, W., Gronich, N., Barnett‐Griness, O., and Rennert, G.
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- 2016
- Full Text
- View/download PDF
4. Neutrophil to lymphocyte ratio and risk of a first episode of stroke in patients with atrial fibrillation: a cohort study
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Saliba, W., Barnett‐Griness, O., Elias, M., and Rennert, G.
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- 2015
- Full Text
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5. Statins use and risk of mortality in patient with Clostridium difficile infection
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Saliba, W., Barnett-Griness, O., Elias, M., and Rennert, G.
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- 2014
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- View/download PDF
6. SO-35 T-cell abundance measured by immunoSEQ predicts overall survival in colorectal cancer
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Gruber, S., primary, Idos, G., additional, Bonner, J., additional, Lindsey, S., additional, Rennert, H., additional, and Rennert, G., additional
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- 2022
- Full Text
- View/download PDF
7. A prospective prostate cancer screening programme for men with pathogenic variants in mismatch repair genes (IMPACT): initial results from an international prospective study.
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Bancroft E.K., Page E.C., Brook M.N., Thomas S., Taylor N., Pope J., McHugh J., Jones A.-B., Karlsson Q., Merson S., Ong K.R., Hoffman J., Huber C., Maehle L., Grindedal E.M., Stormorken A., Evans D.G., Rothwell J., Lalloo F., Brady A.F., Bartlett M., Snape K., Hanson H., James P., McKinley J., Mascarenhas L., Syngal S., Ukaegbu C., Side L., Thomas T., Barwell J., Teixeira M.R., Izatt L., Suri M., Macrae F.A., Poplawski N., Chen-Shtoyerman R., Ahmed M., Musgrave H., Nicolai N., Greenhalgh L., Brewer C., Pachter N., Spigelman A.D., Azzabi A., Helfand B.T., Halliday D., Buys S., Ramon Y Cajal T., Donaldson A., Cooney K.A., Harris M., McGrath J., Davidson R., Taylor A., Cooke P., Myhill K., Hogben M., Aaronson N.K., Ardern-Jones A., Bangma C.H., Castro E., Dearnaley D., Dias A., Dudderidge T., Eccles D.M., Green K., Eyfjord J., Falconer A., Foster C.S., Gronberg H., Hamdy F.C., Johannsson O., Khoo V., Lilja H., Lindeman G.J., Lubinski J., Axcrona K., Mikropoulos C., Mitra A.V., Moynihan C., Ni Raghallaigh H., Rennert G., Collier R., Offman J., Kote-Jarai Z., Eeles R.A., Bancroft E.K., Page E.C., Brook M.N., Thomas S., Taylor N., Pope J., McHugh J., Jones A.-B., Karlsson Q., Merson S., Ong K.R., Hoffman J., Huber C., Maehle L., Grindedal E.M., Stormorken A., Evans D.G., Rothwell J., Lalloo F., Brady A.F., Bartlett M., Snape K., Hanson H., James P., McKinley J., Mascarenhas L., Syngal S., Ukaegbu C., Side L., Thomas T., Barwell J., Teixeira M.R., Izatt L., Suri M., Macrae F.A., Poplawski N., Chen-Shtoyerman R., Ahmed M., Musgrave H., Nicolai N., Greenhalgh L., Brewer C., Pachter N., Spigelman A.D., Azzabi A., Helfand B.T., Halliday D., Buys S., Ramon Y Cajal T., Donaldson A., Cooney K.A., Harris M., McGrath J., Davidson R., Taylor A., Cooke P., Myhill K., Hogben M., Aaronson N.K., Ardern-Jones A., Bangma C.H., Castro E., Dearnaley D., Dias A., Dudderidge T., Eccles D.M., Green K., Eyfjord J., Falconer A., Foster C.S., Gronberg H., Hamdy F.C., Johannsson O., Khoo V., Lilja H., Lindeman G.J., Lubinski J., Axcrona K., Mikropoulos C., Mitra A.V., Moynihan C., Ni Raghallaigh H., Rennert G., Collier R., Offman J., Kote-Jarai Z., and Eeles R.A.
- Abstract
BACKGROUND: Lynch syndrome is a rare familial cancer syndrome caused by pathogenic variants in the mismatch repair genes MLH1, MSH2, MSH6, or PMS2, that cause predisposition to various cancers, predominantly colorectal and endometrial cancer. Data are emerging that pathogenic variants in mismatch repair genes increase the risk of early-onset aggressive prostate cancer. The IMPACT study is prospectively assessing prostate-specific antigen (PSA) screening in men with germline mismatch repair pathogenic variants. Here, we report the usefulness of PSA screening, prostate cancer incidence, and tumour characteristics after the first screening round in men with and without these germline pathogenic variants. METHOD(S): The IMPACT study is an international, prospective study. Men aged 40-69 years without a previous prostate cancer diagnosis and with a known germline pathogenic variant in the MLH1, MSH2, or MSH6 gene, and age-matched male controls who tested negative for a familial pathogenic variant in these genes were recruited from 34 genetic and urology clinics in eight countries, and underwent a baseline PSA screening. Men who had a PSA level higher than 3.0 ng/mL were offered a transrectal, ultrasound-guided, prostate biopsy and a histopathological analysis was done. All participants are undergoing a minimum of 5 years' annual screening. The primary endpoint was to determine the incidence, stage, and pathology of screening-detected prostate cancer in carriers of pathogenic variants compared with non-carrier controls. We used Fisher's exact test to compare the number of cases, cancer incidence, and positive predictive values of the PSA cutoff and biopsy between carriers and non-carriers and the differences between disease types (ie, cancer vs no cancer, clinically significant cancer vs no cancer). We assessed screening outcomes and tumour characteristics by pathogenic variant status. Here we present results from the first round of PSA screening in the IMPACT study. This
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- 2022
8. A genome-wide gene-based gene-environment interaction study of breast cancer in more than 90,000 women.
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Wang, X, Chen, H, Middha Kapoor, P, Su, Y-R, Bolla, MK, Dennis, J, Dunning, AM, Lush, M, Wang, Q, Michailidou, K, Pharoah, PDP, Hopper, JL, Southey, MC, Koutros, S, Beane Freeman, LE, Stone, J, Rennert, G, Shibli, R, Murphy, RA, Aronson, K, Guénel, P, Truong, T, Teras, LR, Hodge, JM, Canzian, F, Kaaks, R, Brenner, H, Arndt, V, Hoppe, R, Lo, W-Y, Behrens, S, Mannermaa, A, Kosma, V-M, Jung, A, Becher, H, Giles, GG, Haiman, CA, Maskarinec, G, Scott, C, Winham, S, Simard, J, Goldberg, MS, Zheng, W, Long, J, Troester, MA, Love, MI, Peng, C, Tamimi, R, Eliassen, H, García-Closas, M, Figueroa, J, Ahearn, T, Yang, R, Evans, DG, Howell, A, Hall, P, Czene, K, Wolk, A, Sandler, DP, Taylor, JA, Swerdlow, AJ, Orr, N, Lacey, JV, Wang, S, Olsson, H, Easton, DF, Milne, RL, Hsu, L, Kraft, P, Chang-Claude, J, Lindström, S, Wang, X, Chen, H, Middha Kapoor, P, Su, Y-R, Bolla, MK, Dennis, J, Dunning, AM, Lush, M, Wang, Q, Michailidou, K, Pharoah, PDP, Hopper, JL, Southey, MC, Koutros, S, Beane Freeman, LE, Stone, J, Rennert, G, Shibli, R, Murphy, RA, Aronson, K, Guénel, P, Truong, T, Teras, LR, Hodge, JM, Canzian, F, Kaaks, R, Brenner, H, Arndt, V, Hoppe, R, Lo, W-Y, Behrens, S, Mannermaa, A, Kosma, V-M, Jung, A, Becher, H, Giles, GG, Haiman, CA, Maskarinec, G, Scott, C, Winham, S, Simard, J, Goldberg, MS, Zheng, W, Long, J, Troester, MA, Love, MI, Peng, C, Tamimi, R, Eliassen, H, García-Closas, M, Figueroa, J, Ahearn, T, Yang, R, Evans, DG, Howell, A, Hall, P, Czene, K, Wolk, A, Sandler, DP, Taylor, JA, Swerdlow, AJ, Orr, N, Lacey, JV, Wang, S, Olsson, H, Easton, DF, Milne, RL, Hsu, L, Kraft, P, Chang-Claude, J, and Lindström, S
- Abstract
BACKGROUND: Genome-wide association studies (GWAS) have identified more than 200 susceptibility loci for breast cancer, but these variants explain less than a fifth of the disease risk. Although gene-environment interactions have been proposed to account for some of the remaining heritability, few studies have empirically assessed this. METHODS: We obtained genotype and risk factor data from 46,060 cases and 47,929 controls of European ancestry from population-based studies within the Breast Cancer Association Consortium (BCAC). We built gene expression prediction models for 4,864 genes with a significant (P<0.01) heritable component using the transcriptome and genotype data from the Genotype-Tissue Expression (GTEx) project. We leveraged predicted gene expression information to investigate the interactions between gene-centric genetic variation and 14 established risk factors in association with breast cancer risk, using a mixed-effects score test. RESULTS: After adjusting for number of tests using Bonferroni correction, no interaction remained statistically significant. The strongest interaction observed was between the predicted expression of the C13orf45 gene and age at first full-term pregnancy (PGXE=4.44×10-6). CONCLUSION: In this transcriptome-informed genome-wide gene-environment interaction study of breast cancer, we found no strong support for the role of gene expression in modifying the associations between established risk factors and breast cancer risk. IMPACT: Our study suggests a limited role of gene-environment interactions in breast cancer risk.
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- 2022
9. Common variants in breast cancer risk loci predispose to distinct tumor subtypes
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Ahearn, TU, Zhang, H, Michailidou, K, Milne, RL, Bolla, MK, Dennis, J, Dunning, AM, Lush, M, Wang, Q, Andrulis, IL, Anton-Culver, H, Arndt, V, Aronson, KJ, Auer, PL, Augustinsson, A, Baten, A, Becher, H, Behrens, S, Benitez, J, Bermisheva, M, Blomqvist, C, Bojesen, SE, Bonanni, B, Borresen-Dale, A-L, Brauch, H, Brenner, H, Brooks-Wilson, A, Bruening, T, Burwinkel, B, Buys, SS, Canzian, F, Castelao, JE, Chang-Claude, J, Chanock, SJ, Chenevix-Trench, G, Clarke, CL, Collee, JM, Cox, A, Cross, SS, Czene, K, Daly, MB, Devilee, P, Dork, T, Dwek, M, Eccles, DM, Evans, DG, Fasching, PA, Figueroa, J, Floris, G, Gago-Dominguez, M, Gapstur, SM, Garcia-Saenz, JA, Gaudet, MM, Giles, GG, Goldberg, MS, Gonzalez-Neira, A, Alnaes, GIG, Grip, M, Guenel, P, Haiman, CA, Hall, P, Hamann, U, Harkness, EF, Heemskerk-Gerritsen, BAM, Holleczek, B, Hollestelle, A, Hooning, MJ, Hoover, RN, Hopper, JL, Howell, A, Jakimovska, M, Jakubowska, A, John, EM, Jones, ME, Jung, A, Kaaks, R, Kauppila, S, Keeman, R, Khusnutdinova, E, Kitahara, CM, Ko, Y-D, Koutros, S, Kristensen, VN, Kruger, U, Kubelka-Sabit, K, Kurian, AW, Kyriacou, K, Lambrechts, D, Lee, DG, Lindblom, A, Linet, M, Lissowska, J, Llaneza, A, Lo, W-Y, MacInnis, RJ, Mannermaa, A, Manoochehri, M, Margolin, S, Martinez, ME, McLean, C, Meindl, A, Menon, U, Nevanlinna, H, Newman, WG, Nodora, J, Offit, K, Olsson, H, Orr, N, Park-Simon, T-W, Patel, A, Peto, J, Pita, G, Plaseska-Karanfilska, D, Prentice, R, Punie, K, Pylkas, K, Radice, P, Rennert, G, Romero, A, Ruediger, T, Saloustros, E, Sampson, S, Sandler, DP, Sawyer, EJ, Schmutzler, RK, Schoemaker, MJ, Schottker, B, Sherman, ME, Shu, X-O, Smichkoska, S, Southey, MC, Spinelli, JJ, Swerdlow, AJ, Tamimi, RM, Tapper, WJ, Taylor, JA, Teras, LR, Terry, MB, Torres, D, Troester, MA, Vachon, CM, van Deurzen, CHM, van Veen, EM, Wagner, P, Weinberg, CR, Wendt, C, Wesseling, J, Winqvist, R, Wolk, A, Yang, XR, Zheng, W, Couch, FJ, Simard, J, Kraft, P, Easton, DF, Pharoah, PDP, Schmidt, MK, Garcia-Closas, M, Chatterjee, N, Ahearn, TU, Zhang, H, Michailidou, K, Milne, RL, Bolla, MK, Dennis, J, Dunning, AM, Lush, M, Wang, Q, Andrulis, IL, Anton-Culver, H, Arndt, V, Aronson, KJ, Auer, PL, Augustinsson, A, Baten, A, Becher, H, Behrens, S, Benitez, J, Bermisheva, M, Blomqvist, C, Bojesen, SE, Bonanni, B, Borresen-Dale, A-L, Brauch, H, Brenner, H, Brooks-Wilson, A, Bruening, T, Burwinkel, B, Buys, SS, Canzian, F, Castelao, JE, Chang-Claude, J, Chanock, SJ, Chenevix-Trench, G, Clarke, CL, Collee, JM, Cox, A, Cross, SS, Czene, K, Daly, MB, Devilee, P, Dork, T, Dwek, M, Eccles, DM, Evans, DG, Fasching, PA, Figueroa, J, Floris, G, Gago-Dominguez, M, Gapstur, SM, Garcia-Saenz, JA, Gaudet, MM, Giles, GG, Goldberg, MS, Gonzalez-Neira, A, Alnaes, GIG, Grip, M, Guenel, P, Haiman, CA, Hall, P, Hamann, U, Harkness, EF, Heemskerk-Gerritsen, BAM, Holleczek, B, Hollestelle, A, Hooning, MJ, Hoover, RN, Hopper, JL, Howell, A, Jakimovska, M, Jakubowska, A, John, EM, Jones, ME, Jung, A, Kaaks, R, Kauppila, S, Keeman, R, Khusnutdinova, E, Kitahara, CM, Ko, Y-D, Koutros, S, Kristensen, VN, Kruger, U, Kubelka-Sabit, K, Kurian, AW, Kyriacou, K, Lambrechts, D, Lee, DG, Lindblom, A, Linet, M, Lissowska, J, Llaneza, A, Lo, W-Y, MacInnis, RJ, Mannermaa, A, Manoochehri, M, Margolin, S, Martinez, ME, McLean, C, Meindl, A, Menon, U, Nevanlinna, H, Newman, WG, Nodora, J, Offit, K, Olsson, H, Orr, N, Park-Simon, T-W, Patel, A, Peto, J, Pita, G, Plaseska-Karanfilska, D, Prentice, R, Punie, K, Pylkas, K, Radice, P, Rennert, G, Romero, A, Ruediger, T, Saloustros, E, Sampson, S, Sandler, DP, Sawyer, EJ, Schmutzler, RK, Schoemaker, MJ, Schottker, B, Sherman, ME, Shu, X-O, Smichkoska, S, Southey, MC, Spinelli, JJ, Swerdlow, AJ, Tamimi, RM, Tapper, WJ, Taylor, JA, Teras, LR, Terry, MB, Torres, D, Troester, MA, Vachon, CM, van Deurzen, CHM, van Veen, EM, Wagner, P, Weinberg, CR, Wendt, C, Wesseling, J, Winqvist, R, Wolk, A, Yang, XR, Zheng, W, Couch, FJ, Simard, J, Kraft, P, Easton, DF, Pharoah, PDP, Schmidt, MK, Garcia-Closas, M, and Chatterjee, N
- Abstract
BACKGROUND: Genome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear. METHODS: Among 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes. RESULTS: Eighty-five of 173 variants were associated with at least one tumor feature (false discovery rate < 5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at p < 0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions. CONCLUSION: This report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction.
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- 2022
10. Rare germline copy number variants (CNVs) and breast cancer risk
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Dennis, J, Tyrer, JP, Walker, LC, Michailidou, K, Dorling, L, Bolla, MK, Wang, Q, Ahearn, TU, Andrulis, IL, Anton-Culver, H, Antonenkova, NN, Arndt, V, Aronson, KJ, Freeman, LEB, Beckmann, MW, Behrens, S, Benitez, J, Bermisheva, M, Bogdanova, N, Bojesen, SE, Brenner, H, Castelao, JE, Chang-Claude, J, Chenevix-Trench, G, Clarke, CL, Collee, JM, Couch, FJ, Cox, A, Cross, SS, Czene, K, Devilee, P, Dork, T, Dossus, L, Eliassen, AH, Eriksson, M, Evans, DG, Fasching, PA, Figueroa, J, Fletcher, O, Flyger, H, Fritschi, L, Gabrielson, M, Gago-Dominguez, M, Garcia-Closas, M, Giles, GG, Gonzalez-Neira, A, Guenel, P, Hahnen, E, Haiman, CA, Hall, P, Hollestelle, A, Hoppe, R, Hopper, JL, Howell, A, Jager, A, Jakubowska, A, John, EM, Johnson, N, Jones, ME, Jung, A, Kaaks, R, Keeman, R, Khusnutdinova, E, Kitahara, CM, Ko, Y-D, Kosma, V-M, Koutros, S, Kraft, P, Kristensen, VN, Kubelka-Sabit, K, Kurian, AW, Lacey, J, Lambrechts, D, Larson, NL, Linet, M, Ogrodniczak, A, Mannermaa, A, Manoukian, S, Margolin, S, Mavroudis, D, Milne, RL, Muranen, TA, Murphy, RA, Nevanlinna, H, Olson, JE, Olsson, H, Park-Simon, T-W, Perou, CM, Peterlongo, P, Plaseska-Karanfilska, D, Pylkas, K, Rennert, G, Saloustros, E, Sandler, DP, Sawyer, EJ, Schmidt, MK, Schmutzler, RK, Shibli, R, Smeets, A, Soucy, P, Southey, MC, Swerdlow, AJ, Tamimi, RM, Taylor, JA, Teras, LR, Terry, MB, Tomlinson, I, Troester, MA, Truong, T, Vachon, CM, Wendt, C, Winqvist, R, Wolk, A, Yang, XR, Zheng, W, Ziogas, A, Simard, J, Dunning, AM, Pharoah, PDP, Easton, DF, Dennis, J, Tyrer, JP, Walker, LC, Michailidou, K, Dorling, L, Bolla, MK, Wang, Q, Ahearn, TU, Andrulis, IL, Anton-Culver, H, Antonenkova, NN, Arndt, V, Aronson, KJ, Freeman, LEB, Beckmann, MW, Behrens, S, Benitez, J, Bermisheva, M, Bogdanova, N, Bojesen, SE, Brenner, H, Castelao, JE, Chang-Claude, J, Chenevix-Trench, G, Clarke, CL, Collee, JM, Couch, FJ, Cox, A, Cross, SS, Czene, K, Devilee, P, Dork, T, Dossus, L, Eliassen, AH, Eriksson, M, Evans, DG, Fasching, PA, Figueroa, J, Fletcher, O, Flyger, H, Fritschi, L, Gabrielson, M, Gago-Dominguez, M, Garcia-Closas, M, Giles, GG, Gonzalez-Neira, A, Guenel, P, Hahnen, E, Haiman, CA, Hall, P, Hollestelle, A, Hoppe, R, Hopper, JL, Howell, A, Jager, A, Jakubowska, A, John, EM, Johnson, N, Jones, ME, Jung, A, Kaaks, R, Keeman, R, Khusnutdinova, E, Kitahara, CM, Ko, Y-D, Kosma, V-M, Koutros, S, Kraft, P, Kristensen, VN, Kubelka-Sabit, K, Kurian, AW, Lacey, J, Lambrechts, D, Larson, NL, Linet, M, Ogrodniczak, A, Mannermaa, A, Manoukian, S, Margolin, S, Mavroudis, D, Milne, RL, Muranen, TA, Murphy, RA, Nevanlinna, H, Olson, JE, Olsson, H, Park-Simon, T-W, Perou, CM, Peterlongo, P, Plaseska-Karanfilska, D, Pylkas, K, Rennert, G, Saloustros, E, Sandler, DP, Sawyer, EJ, Schmidt, MK, Schmutzler, RK, Shibli, R, Smeets, A, Soucy, P, Southey, MC, Swerdlow, AJ, Tamimi, RM, Taylor, JA, Teras, LR, Terry, MB, Tomlinson, I, Troester, MA, Truong, T, Vachon, CM, Wendt, C, Winqvist, R, Wolk, A, Yang, XR, Zheng, W, Ziogas, A, Simard, J, Dunning, AM, Pharoah, PDP, and Easton, DF
- Abstract
Germline copy number variants (CNVs) are pervasive in the human genome but potential disease associations with rare CNVs have not been comprehensively assessed in large datasets. We analysed rare CNVs in genes and non-coding regions for 86,788 breast cancer cases and 76,122 controls of European ancestry with genome-wide array data. Gene burden tests detected the strongest association for deletions in BRCA1 (P = 3.7E-18). Nine other genes were associated with a p-value < 0.01 including known susceptibility genes CHEK2 (P = 0.0008), ATM (P = 0.002) and BRCA2 (P = 0.008). Outside the known genes we detected associations with p-values < 0.001 for either overall or subtype-specific breast cancer at nine deletion regions and four duplication regions. Three of the deletion regions were in established common susceptibility loci. To the best of our knowledge, this is the first genome-wide analysis of rare CNVs in a large breast cancer case-control dataset. We detected associations with exonic deletions in established breast cancer susceptibility genes. We also detected suggestive associations with non-coding CNVs in known and novel loci with large effects sizes. Larger sample sizes will be required to reach robust levels of statistical significance.
- Published
- 2022
11. Incorporating progesterone receptor expression into the PREDICT breast prognostic model
- Author
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Grootes, I, Keeman, R, Blows, FM, Milne, RL, Giles, GG, Swerdlow, AJ, Fasching, PA, Abubakar, M, Andrulis, IL, Anton-Culver, H, Beckmann, MW, Blomqvist, C, Bojesen, SE, Bolla, MK, Bonanni, B, Briceno, I, Burwinkel, B, Camp, NJ, Castelao, JE, Choi, J-Y, Clarke, CL, Couch, FJ, Cox, A, Cross, SS, Czene, K, Devilee, P, Dork, T, Dunning, AM, Dwek, M, Easton, DF, Eccles, DM, Eriksson, M, Ernst, K, Evans, DG, Figueroa, JD, Fink, V, Floris, G, Fox, S, Gabrielson, M, Gago-Dominguez, M, Garcia-Saenz, JA, Gonzalez-Neira, A, Haeberle, L, Haiman, CA, Hall, P, Hamann, U, Harkness, EF, Hartman, M, Hein, A, Hooning, MJ, Hou, M-F, Howell, SJ, Ito, H, Jakubowska, A, Janni, W, John, EM, Jung, A, Kang, D, Kristensen, VN, Kwong, A, Lambrechts, D, Li, J, Manoochehri, M, Margolin, S, Matsuo, K, Taib, NAM, Mulligan, AM, Nevanlinna, H, Newman, WG, Offit, K, Osorio, A, Park, SK, Park-Simon, T-W, Patel, A, Presneau, N, Pylkas, K, Rack, B, Radice, P, Rennert, G, Romero, A, Saloustros, E, Sawyer, EJ, Schneeweiss, A, Schochter, F, Schoemaker, MJ, Shen, C-Y, Shibli, R, Sinn, P, Tapper, WJ, Tawfiq, E, Teo, SH, Teras, LR, Torres, D, Vachon, CM, van Deurzen, CHM, Wendt, C, Williams, JA, Winqvist, R, Elwood, M, Schmidt, MK, Pharoah, PDP, Grootes, I, Keeman, R, Blows, FM, Milne, RL, Giles, GG, Swerdlow, AJ, Fasching, PA, Abubakar, M, Andrulis, IL, Anton-Culver, H, Beckmann, MW, Blomqvist, C, Bojesen, SE, Bolla, MK, Bonanni, B, Briceno, I, Burwinkel, B, Camp, NJ, Castelao, JE, Choi, J-Y, Clarke, CL, Couch, FJ, Cox, A, Cross, SS, Czene, K, Devilee, P, Dork, T, Dunning, AM, Dwek, M, Easton, DF, Eccles, DM, Eriksson, M, Ernst, K, Evans, DG, Figueroa, JD, Fink, V, Floris, G, Fox, S, Gabrielson, M, Gago-Dominguez, M, Garcia-Saenz, JA, Gonzalez-Neira, A, Haeberle, L, Haiman, CA, Hall, P, Hamann, U, Harkness, EF, Hartman, M, Hein, A, Hooning, MJ, Hou, M-F, Howell, SJ, Ito, H, Jakubowska, A, Janni, W, John, EM, Jung, A, Kang, D, Kristensen, VN, Kwong, A, Lambrechts, D, Li, J, Manoochehri, M, Margolin, S, Matsuo, K, Taib, NAM, Mulligan, AM, Nevanlinna, H, Newman, WG, Offit, K, Osorio, A, Park, SK, Park-Simon, T-W, Patel, A, Presneau, N, Pylkas, K, Rack, B, Radice, P, Rennert, G, Romero, A, Saloustros, E, Sawyer, EJ, Schneeweiss, A, Schochter, F, Schoemaker, MJ, Shen, C-Y, Shibli, R, Sinn, P, Tapper, WJ, Tawfiq, E, Teo, SH, Teras, LR, Torres, D, Vachon, CM, van Deurzen, CHM, Wendt, C, Williams, JA, Winqvist, R, Elwood, M, Schmidt, MK, and Pharoah, PDP
- Abstract
BACKGROUND: Predict Breast (www.predict.nhs.uk) is an online prognostication and treatment benefit tool for early invasive breast cancer. The aim of this study was to incorporate the prognostic effect of progesterone receptor (PR) status into a new version of PREDICT and to compare its performance to the current version (2.2). METHOD: The prognostic effect of PR status was based on the analysis of data from 45,088 European patients with breast cancer from 49 studies in the Breast Cancer Association Consortium. Cox proportional hazard models were used to estimate the hazard ratio for PR status. Data from a New Zealand study of 11,365 patients with early invasive breast cancer were used for external validation. Model calibration and discrimination were used to test the model performance. RESULTS: Having a PR-positive tumour was associated with a 23% and 28% lower risk of dying from breast cancer for women with oestrogen receptor (ER)-negative and ER-positive breast cancer, respectively. The area under the ROC curve increased with the addition of PR status from 0.807 to 0.809 for patients with ER-negative tumours (p = 0.023) and from 0.898 to 0.902 for patients with ER-positive tumours (p = 2.3 × 10-6) in the New Zealand cohort. Model calibration was modest with 940 observed deaths compared to 1151 predicted. CONCLUSION: The inclusion of the prognostic effect of PR status to PREDICT Breast has led to an improvement of model performance and more accurate absolute treatment benefit predictions for individual patients. Further studies should determine whether the baseline hazard function requires recalibration.
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- 2022
12. Interactions between folate intake and genetic predictors of gene expression levels associated with colorectal cancer risk
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Haas, CB, Su, Y-R, Petersen, P, Wang, X, Bien, SA, Lin, Y, Albanes, D, Weinstein, SJ, Jenkins, MA, Figueiredo, JC, Newcomb, PA, Casey, G, Le Marchand, L, Campbell, PT, Moreno, V, Potter, JD, Sakoda, LC, Slattery, ML, Chan, AT, Li, L, Giles, GG, Milne, RL, Gruber, SB, Rennert, G, Woods, MO, Gallinger, SJ, Berndt, S, Hayes, RB, Huang, W-Y, Wolk, A, White, E, Nan, H, Nassir, R, Lindor, NM, Lewinger, JP, Kim, AE, Conti, D, Gauderman, WJ, Buchanan, DD, Peters, U, Hsu, L, Haas, CB, Su, Y-R, Petersen, P, Wang, X, Bien, SA, Lin, Y, Albanes, D, Weinstein, SJ, Jenkins, MA, Figueiredo, JC, Newcomb, PA, Casey, G, Le Marchand, L, Campbell, PT, Moreno, V, Potter, JD, Sakoda, LC, Slattery, ML, Chan, AT, Li, L, Giles, GG, Milne, RL, Gruber, SB, Rennert, G, Woods, MO, Gallinger, SJ, Berndt, S, Hayes, RB, Huang, W-Y, Wolk, A, White, E, Nan, H, Nassir, R, Lindor, NM, Lewinger, JP, Kim, AE, Conti, D, Gauderman, WJ, Buchanan, DD, Peters, U, and Hsu, L
- Abstract
Observational studies have shown higher folate consumption to be associated with lower risk of colorectal cancer (CRC). Understanding whether and how genetic risk factors interact with folate could further elucidate the underlying mechanism. Aggregating functionally relevant genetic variants in set-based variant testing has higher power to detect gene-environment (G × E) interactions and may provide information on the underlying biological pathway. We investigated interactions between folate consumption and predicted gene expression on colorectal cancer risk across the genome. We used variant weights from the PrediXcan models of colon tissue-specific gene expression as a priori variant information for a set-based G × E approach. We harmonized total folate intake (mcg/day) based on dietary intake and supplemental use across cohort and case-control studies and calculated sex and study specific quantiles. Analyses were performed using a mixed effects score tests for interactions between folate and genetically predicted expression of 4839 genes with available genetically predicted expression. We pooled results across 23 studies for a total of 13,498 cases with colorectal tumors and 13,918 controls of European ancestry. We used a false discovery rate of 0.2 to identify genes with suggestive evidence of an interaction. We found suggestive evidence of interaction with folate intake on CRC risk for genes including glutathione S-Transferase Alpha 1 (GSTA1; p = 4.3E-4), Tonsuko Like, DNA Repair Protein (TONSL; p = 4.3E-4), and Aspartylglucosaminidase (AGA: p = 4.5E-4). We identified three genes involved in preventing or repairing DNA damage that may interact with folate consumption to alter CRC risk. Glutathione is an antioxidant, preventing cellular damage and is a downstream metabolite of homocysteine and metabolized by GSTA1. TONSL is part of a complex that functions in the recovery of double strand breaks and AGA plays a role in lysosomal breakdown of glycoprotein.
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- 2022
13. Distinct Reproductive Risk Profiles for Intrinsic-Like Breast Cancer Subtypes: Pooled Analysis of Population-Based Studies
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Jung, AY, Ahearn, TU, Behrens, S, Middha, P, Bolla, MK, Wang, Q, Arndt, V, Aronson, KJ, Augustinsson, A, Freeman, LEB, Becher, H, Brenner, H, Canzian, F, Carey, LA, Consortium, C, Czene, K, Eliassen, AH, Eriksson, M, Evans, DG, Figueroa, JD, Fritschi, L, Gabrielson, M, Giles, GG, Guenel, P, Hadjisavvas, A, Haiman, CA, Hakansson, N, Hall, P, Hamann, U, Hoppe, R, Hopper, JL, Howell, A, Hunter, DJ, Huesing, A, Kaaks, R, Kosma, V-M, Koutros, S, Kraft, P, Lacey, J, Le Marchand, L, Lissowska, J, Loizidou, MA, Mannermaa, A, Maurer, T, Murphy, RA, Olshan, AF, Olsson, H, Patel, A, Perou, CM, Rennert, G, Shibli, R, Shu, X-O, Southey, MC, Stone, J, Tamimi, RM, Teras, LR, Troester, MA, Truong, T, Vachon, CM, Wang, SS, Wolk, A, Wu, AH, Yang, XR, Zheng, W, Dunning, AM, Pharoah, PDP, Easton, DF, Milne, RL, Chatterjee, N, Schmidt, MK, Garcia-Closas, M, Chang-Claude, J, Jung, AY, Ahearn, TU, Behrens, S, Middha, P, Bolla, MK, Wang, Q, Arndt, V, Aronson, KJ, Augustinsson, A, Freeman, LEB, Becher, H, Brenner, H, Canzian, F, Carey, LA, Consortium, C, Czene, K, Eliassen, AH, Eriksson, M, Evans, DG, Figueroa, JD, Fritschi, L, Gabrielson, M, Giles, GG, Guenel, P, Hadjisavvas, A, Haiman, CA, Hakansson, N, Hall, P, Hamann, U, Hoppe, R, Hopper, JL, Howell, A, Hunter, DJ, Huesing, A, Kaaks, R, Kosma, V-M, Koutros, S, Kraft, P, Lacey, J, Le Marchand, L, Lissowska, J, Loizidou, MA, Mannermaa, A, Maurer, T, Murphy, RA, Olshan, AF, Olsson, H, Patel, A, Perou, CM, Rennert, G, Shibli, R, Shu, X-O, Southey, MC, Stone, J, Tamimi, RM, Teras, LR, Troester, MA, Truong, T, Vachon, CM, Wang, SS, Wolk, A, Wu, AH, Yang, XR, Zheng, W, Dunning, AM, Pharoah, PDP, Easton, DF, Milne, RL, Chatterjee, N, Schmidt, MK, Garcia-Closas, M, and Chang-Claude, J
- Abstract
BACKGROUND: Reproductive factors have been shown to be differentially associated with risk of estrogen receptor (ER)-positive and ER-negative breast cancer. However, their associations with intrinsic-like subtypes are less clear. METHODS: Analyses included up to 23 353 cases and 71 072 controls pooled from 31 population-based case-control or cohort studies in the Breast Cancer Association Consortium across 16 countries on 4 continents. Polytomous logistic regression was used to estimate the association between reproductive factors and risk of breast cancer by intrinsic-like subtypes (luminal A-like, luminal B-like, luminal B-HER2-like, HER2-enriched-like, and triple-negative breast cancer) and by invasiveness. All statistical tests were 2-sided. RESULTS: Compared with nulliparous women, parous women had a lower risk of luminal A-like, luminal B-like, luminal B-HER2-like, and HER2-enriched-like disease. This association was apparent only after approximately 10 years since last birth and became stronger with increasing time (odds ratio [OR] = 0.59, 95% confidence interval [CI] = 0.49 to 0.71; and OR = 0.36, 95% CI = 0.28 to 0.46 for multiparous women with luminal A-like tumors 20 to less than 25 years after last birth and 45 to less than 50 years after last birth, respectively). In contrast, parous women had a higher risk of triple-negative breast cancer right after their last birth (for multiparous women: OR = 3.12, 95% CI = 2.02 to 4.83) that was attenuated with time but persisted for decades (OR = 1.03, 95% CI = 0.79 to 1.34, for multiparous women 25 to less than 30 years after last birth). Older age at first birth (Pheterogeneity < .001 for triple-negative compared with luminal A-like breast cancer) and breastfeeding (Pheterogeneity < .001 for triple-negative compared with luminal A-like breast cancer) were associated with lower risk of triple-negative breast cancer but not with other disease subtypes. Younger age at menarche was associated with higher risk of all
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- 2022
14. Physical activity, sedentary time and breast cancer risk: a Mendelian randomisation study
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Dixon-Suen, SC, Lewis, SJ, Martin, RM, English, DR, Boyle, T, Giles, GG, Michailidou, K, Bolla, MK, Wang, Q, Dennis, J, Lush, M, Ahearn, TU, Ambrosone, CB, Andrulis, IL, Anton-Culver, H, Arndt, V, Aronson, KJ, Augustinsson, A, Auvinen, P, Beane Freeman, LE, Becher, H, Beckmann, MW, Behrens, S, Bermisheva, M, Blomqvist, C, Bogdanova, N, Bojesen, SE, Bonanni, B, Brenner, H, Bruening, T, Buys, SS, Camp, NJ, Campa, D, Canzian, F, Castelao, JE, Cessna, MH, Chang-Claude, J, Chanock, SJ, Clarke, CL, Conroy, DM, Couch, FJ, Cox, A, Cross, SS, Czene, K, Daly, MB, Devilee, P, Doerk, T, Dwek, M, Eccles, DM, Eliassen, AH, Engel, C, Eriksson, M, Evans, DG, Fasching, PA, Fletcher, O, Flyger, H, Fritschi, L, Gabrielson, M, Gago-Dominguez, M, Garcia-Closas, M, Garcia-Saenz, JA, Goldberg, MS, Guenel, P, Guendert, M, Hahnen, E, Haiman, CA, Haeberle, L, Hakansson, N, Hall, P, Hamann, U, Hart, SN, Harvie, M, Hillemanns, P, Hollestelle, A, Hooning, MJ, Hoppe, R, Hopper, J, Howell, A, Hunter, DJ, Jakubowska, A, Janni, W, John, EM, Jung, A, Kaaks, R, Keeman, R, Kitahara, CM, Koutros, S, Kraft, P, Kristensen, VN, Kubelka-Sabit, K, Kurian, AW, Lacey, J, Lambrechts, D, Le Marchand, L, Lindblom, A, Loibl, S, Lubinski, J, Mannermaa, A, Manoochehri, M, Margolin, S, Martinez, ME, Mavroudis, D, Menon, U, Mulligan, AM, Murphy, RA, Nevanlinna, H, Nevelsteen, I, Newman, WG, Offit, K, Olshan, AF, Olsson, H, Orr, N, Patel, A, Peto, J, Plaseska-Karanfilska, D, Presneau, N, Rack, B, Radice, P, Rees-Punia, E, Rennert, G, Rennert, HS, Romero, A, Saloustros, E, Sandler, DP, Schmidt, MK, Schmutzler, RK, Schwentner, L, Scott, C, Shah, M, Shu, X-O, Simard, J, Southey, MC, Stone, J, Surowy, H, Swerdlow, AJ, Tamimi, RM, Tapper, WJ, Taylor, JA, Terry, MB, Tollenaar, RAEM, Troester, MA, Truong, T, Untch, M, Vachon, CM, Joseph, V, Wappenschmidt, B, Weinberg, CR, Wolk, A, Yannoukakos, D, Zheng, W, Ziogas, A, Dunning, AM, Pharoah, PDP, Easton, DF, Milne, RL, Lynch, BM, Dixon-Suen, SC, Lewis, SJ, Martin, RM, English, DR, Boyle, T, Giles, GG, Michailidou, K, Bolla, MK, Wang, Q, Dennis, J, Lush, M, Ahearn, TU, Ambrosone, CB, Andrulis, IL, Anton-Culver, H, Arndt, V, Aronson, KJ, Augustinsson, A, Auvinen, P, Beane Freeman, LE, Becher, H, Beckmann, MW, Behrens, S, Bermisheva, M, Blomqvist, C, Bogdanova, N, Bojesen, SE, Bonanni, B, Brenner, H, Bruening, T, Buys, SS, Camp, NJ, Campa, D, Canzian, F, Castelao, JE, Cessna, MH, Chang-Claude, J, Chanock, SJ, Clarke, CL, Conroy, DM, Couch, FJ, Cox, A, Cross, SS, Czene, K, Daly, MB, Devilee, P, Doerk, T, Dwek, M, Eccles, DM, Eliassen, AH, Engel, C, Eriksson, M, Evans, DG, Fasching, PA, Fletcher, O, Flyger, H, Fritschi, L, Gabrielson, M, Gago-Dominguez, M, Garcia-Closas, M, Garcia-Saenz, JA, Goldberg, MS, Guenel, P, Guendert, M, Hahnen, E, Haiman, CA, Haeberle, L, Hakansson, N, Hall, P, Hamann, U, Hart, SN, Harvie, M, Hillemanns, P, Hollestelle, A, Hooning, MJ, Hoppe, R, Hopper, J, Howell, A, Hunter, DJ, Jakubowska, A, Janni, W, John, EM, Jung, A, Kaaks, R, Keeman, R, Kitahara, CM, Koutros, S, Kraft, P, Kristensen, VN, Kubelka-Sabit, K, Kurian, AW, Lacey, J, Lambrechts, D, Le Marchand, L, Lindblom, A, Loibl, S, Lubinski, J, Mannermaa, A, Manoochehri, M, Margolin, S, Martinez, ME, Mavroudis, D, Menon, U, Mulligan, AM, Murphy, RA, Nevanlinna, H, Nevelsteen, I, Newman, WG, Offit, K, Olshan, AF, Olsson, H, Orr, N, Patel, A, Peto, J, Plaseska-Karanfilska, D, Presneau, N, Rack, B, Radice, P, Rees-Punia, E, Rennert, G, Rennert, HS, Romero, A, Saloustros, E, Sandler, DP, Schmidt, MK, Schmutzler, RK, Schwentner, L, Scott, C, Shah, M, Shu, X-O, Simard, J, Southey, MC, Stone, J, Surowy, H, Swerdlow, AJ, Tamimi, RM, Tapper, WJ, Taylor, JA, Terry, MB, Tollenaar, RAEM, Troester, MA, Truong, T, Untch, M, Vachon, CM, Joseph, V, Wappenschmidt, B, Weinberg, CR, Wolk, A, Yannoukakos, D, Zheng, W, Ziogas, A, Dunning, AM, Pharoah, PDP, Easton, DF, Milne, RL, and Lynch, BM
- Abstract
OBJECTIVES: Physical inactivity and sedentary behaviour are associated with higher breast cancer risk in observational studies, but ascribing causality is difficult. Mendelian randomisation (MR) assesses causality by simulating randomised trial groups using genotype. We assessed whether lifelong physical activity or sedentary time, assessed using genotype, may be causally associated with breast cancer risk overall, pre/post-menopause, and by case-groups defined by tumour characteristics. METHODS: We performed two-sample inverse-variance-weighted MR using individual-level Breast Cancer Association Consortium case-control data from 130 957 European-ancestry women (69 838 invasive cases), and published UK Biobank data (n=91 105-377 234). Genetic instruments were single nucleotide polymorphisms (SNPs) associated in UK Biobank with wrist-worn accelerometer-measured overall physical activity (nsnps=5) or sedentary time (nsnps=6), or accelerometer-measured (nsnps=1) or self-reported (nsnps=5) vigorous physical activity. RESULTS: Greater genetically-predicted overall activity was associated with lower breast cancer overall risk (OR=0.59; 95% confidence interval (CI) 0.42 to 0.83 per-standard deviation (SD;~8 milligravities acceleration)) and for most case-groups. Genetically-predicted vigorous activity was associated with lower risk of pre/perimenopausal breast cancer (OR=0.62; 95% CI 0.45 to 0.87,≥3 vs. 0 self-reported days/week), with consistent estimates for most case-groups. Greater genetically-predicted sedentary time was associated with higher hormone-receptor-negative tumour risk (OR=1.77; 95% CI 1.07 to 2.92 per-SD (~7% time spent sedentary)), with elevated estimates for most case-groups. Results were robust to sensitivity analyses examining pleiotropy (including weighted-median-MR, MR-Egger). CONCLUSION: Our study provides strong evidence that greater overall physical activity, greater vigorous activity, and lower sedentary time are likely to reduce breast cancer r
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- 2022
15. Genome-Wide Interaction Analysis of Genetic Variants With Menopausal Hormone Therapy for Colorectal Cancer Risk
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Tian, Y, Kim, AE, Bien, SA, Lin, Y, Qu, C, Harrison, TA, Carreras-Torres, R, Diez-Obrero, V, Dimou, N, Drew, DA, Hidaka, A, Huyghe, JR, Jordahl, KM, Morrison, J, Murphy, N, Obon-Santacana, M, Ulrich, CM, Ose, J, Peoples, AR, Ruiz-Narvaez, EA, Shcherbina, A, Stern, MC, Su, Y-R, van Duijnhoven, FJB, Arndt, V, Baurley, JW, Berndt, S, Bishop, DT, Brenner, H, Buchanan, DD, Chan, AT, Figueiredo, JC, Gallinger, S, Gruber, SB, Harlid, S, Hoffmeister, M, Jenkins, MA, Joshi, AD, Keku, TO, Larsson, SC, Le Marchand, L, Li, L, Giles, GG, Milne, RL, Nan, H, Nassir, R, Ogino, S, Budiarto, A, Platz, EA, Potter, JD, Prentice, RL, Rennert, G, Sakoda, LC, Schoen, RE, Slattery, ML, Thibodeau, SN, Van Guelpen, B, Visvanathan, K, White, E, Wolk, A, Woods, MO, Wu, AH, Campbell, PT, Casey, G, Conti, D, Gunter, MJ, Kundaje, A, Lewinger, JP, Moreno, V, Newcomb, PA, Pardamean, B, Thomas, DC, Tsilidis, KK, Peters, U, Gauderman, WJ, Hsu, L, Chang-Claude, J, Tian, Y, Kim, AE, Bien, SA, Lin, Y, Qu, C, Harrison, TA, Carreras-Torres, R, Diez-Obrero, V, Dimou, N, Drew, DA, Hidaka, A, Huyghe, JR, Jordahl, KM, Morrison, J, Murphy, N, Obon-Santacana, M, Ulrich, CM, Ose, J, Peoples, AR, Ruiz-Narvaez, EA, Shcherbina, A, Stern, MC, Su, Y-R, van Duijnhoven, FJB, Arndt, V, Baurley, JW, Berndt, S, Bishop, DT, Brenner, H, Buchanan, DD, Chan, AT, Figueiredo, JC, Gallinger, S, Gruber, SB, Harlid, S, Hoffmeister, M, Jenkins, MA, Joshi, AD, Keku, TO, Larsson, SC, Le Marchand, L, Li, L, Giles, GG, Milne, RL, Nan, H, Nassir, R, Ogino, S, Budiarto, A, Platz, EA, Potter, JD, Prentice, RL, Rennert, G, Sakoda, LC, Schoen, RE, Slattery, ML, Thibodeau, SN, Van Guelpen, B, Visvanathan, K, White, E, Wolk, A, Woods, MO, Wu, AH, Campbell, PT, Casey, G, Conti, D, Gunter, MJ, Kundaje, A, Lewinger, JP, Moreno, V, Newcomb, PA, Pardamean, B, Thomas, DC, Tsilidis, KK, Peters, U, Gauderman, WJ, Hsu, L, and Chang-Claude, J
- Abstract
BACKGROUND: The use of menopausal hormone therapy (MHT) may interact with genetic variants to influence colorectal cancer (CRC) risk. METHODS: We conducted a genome-wide, gene-environment interaction between single nucleotide polymorphisms and the use of any MHT, estrogen only, and combined estrogen-progestogen therapy with CRC risk, among 28 486 postmenopausal women (11 519 CRC patients and 16 967 participants without CRC) from 38 studies, using logistic regression, 2-step method, and 2- or 3-degree-of-freedom joint test. A set-based score test was applied for rare genetic variants. RESULTS: The use of any MHT, estrogen only and estrogen-progestogen were associated with a reduced CRC risk (odds ratio [OR] = 0.71, 95% confidence interval [CI] = 0.64 to 0.78; OR = 0.65, 95% CI = 0.53 to 0.79; and OR = 0.73, 95% CI = 0.59 to 0.90, respectively). The 2-step method identified a statistically significant interaction between a GRIN2B variant rs117868593 and MHT use, whereby MHT-associated CRC risk was statistically significantly reduced in women with the GG genotype (OR = 0.68, 95% CI = 0.64 to 0.72) but not within strata of GC or CC genotypes. A statistically significant interaction between a DCBLD1 intronic variant at 6q22.1 (rs10782186) and MHT use was identified by the 2-degree-of-freedom joint test. The MHT-associated CRC risk was reduced with increasing number of rs10782186-C alleles, showing odds ratios of 0.78 (95% CI = 0.70 to 0.87) for TT, 0.68 (95% CI = 0.63 to 0.73) for TC, and 0.66 (95% CI = 0.60 to 0.74) for CC genotypes. In addition, 5 genes in rare variant analysis showed suggestive interactions with MHT (2-sided P < 1.2 × 10-4). CONCLUSION: Genetic variants that modify the association between MHT and CRC risk were identified, offering new insights into pathways of CRC carcinogenesis and potential mechanisms involved.
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- 2022
16. Common variants in breast cancer risk loci predispose to distinct tumor subtypes
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Ahearn, T. U. (Thomas U.), Zhang, H. (Haoyu), Michailidou, K. (Kyriaki), Milne, R. L. (Roger L.), Bolla, M. K. (Manjeet K.), Dennis, J. (Joe), Dunning, A. M. (Alison M.), Lush, M. (Michael), Wang, Q. (Qin), Andrulis, I. L. (Irene L.), Anton-Culver, H. (Hoda), Arndt, V. (Volker), Aronson, K. J. (Kristan J.), Auer, P. L. (Paul L.), Augustinsson, A. (Annelie), Baten, A. (Adinda), Becher, H. (Heiko), Behrens, S. (Sabine), Benitez, J. (Javier), Bermisheva, M. (Marina), Blomqvist, C. (Carl), Bojesen, S. E. (Stig E.), Bonanni, B. (Bernardo), Borresen-Dale, A.-L. (Anne-Lise), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Brooks-Wilson, A. (Angela), Bruening, T. (Thomas), Burwinkel, B. (Barbara), Buys, S. S. (Saundra S.), Canzian, F. (Federico), Castelao, J. E. (Jose E.), Chang-Claude, J. (Jenny), Chanock, S. J. (Stephen J.), Chenevix-Trench, G. (Georgia), Clarke, C. L. (Christine L.), Collee, J. M. (J. Margriet), Cox, A. (Angela), Cross, S. S. (Simon S.), Czene, K. (Kamila), Daly, M. B. (Mary B.), Devilee, P. (Peter), Dork, T. (Thilo), Dwek, M. (Miriam), Eccles, D. M. (Diana M.), Evans, D. G. (D. Gareth), Fasching, P. A. (Peter A.), Figueroa, J. (Jonine), Floris, G. (Giuseppe), Gago-Dominguez, M. (Manuela), Gapstur, S. M. (Susan M.), Garcia-Saenz, J. A. (Jose A.), Gaudet, M. M. (Mia M.), Giles, G. G. (Graham G.), Goldberg, M. S. (Mark S.), Gonzalez-Neira, A. (Anna), Alnaes, G. I. (Grethe I. Grenaker), Grip, M. (Mervi), Guenel, P. (Pascal), Haiman, C. A. (Christopher A.), Hall, P. (Per), Hamann, U. (Ute), Harkness, E. F. (Elaine F.), Heemskerk-Gerritsen, B. A. (Bernadette A. M.), Holleczek, B. (Bernd), Hollestelle, A. (Antoinette), Hooning, M. J. (Maartje J.), Hoover, R. N. (Robert N.), Hopper, J. L. (John L.), Howell, A. (Anthony), Jakimovska, M. (Milena), Jakubowska, A. (Anna), John, E. M. (Esther M.), Jones, M. E. (Michael E.), Jung, A. (Audrey), Kaaks, R. (Rudolf), Kauppila, S. (Saila), Keeman, R. (Renske), Khusnutdinova, E. (Elza), Kitahara, C. M. (Cari M.), Ko, Y.-D. (Yon-Dschun), Koutros, S. (Stella), Kristensen, V. N. (Vessela N.), Kruger, U. (Ute), Kubelka-Sabit, K. (Katerina), Kurian, A. W. (Allison W.), Kyriacou, K. (Kyriacos), Lambrechts, D. (Diether), Lee, D. G. (Derrick G.), Lindblom, A. (Annika), Linet, M. (Martha), Lissowska, J. (Jolanta), Llaneza, A. (Ana), Lo, W.-Y. (Wing-Yee), MacInnis, R. J. (Robert J.), Mannermaa, A. (Arto), Manoochehri, M. (Mehdi), Margolin, S. (Sara), Martinez, M. E. (Maria Elena), McLean, C. (Catriona), Meindl, A. (Alfons), Menon, U. (Usha), Nevanlinna, H. (Heli), Newman, W. G. (William G.), Nodora, J. (Jesse), Offit, K. (Kenneth), Olsson, H. (Hakan), Orr, N. (Nick), Park-Simon, T.-W. (Tjoung-Won), Patel, A. V. (Alpa, V), Peto, J. (Julian), Pita, G. (Guillermo), Plaseska-Karanfilska, D. (Dijana), Prentice, R. (Ross), Punie, K. (Kevin), Pylkas, K. (Katri), Radice, P. (Paolo), Rennert, G. (Gad), Romero, A. (Atocha), Ruediger, T. (Thomas), Saloustros, E. (Emmanouil), Sampson, S. (Sarah), Sandler, D. P. (Dale P.), Sawyer, E. J. (Elinor J.), Schmutzler, R. K. (Rita K.), Schoemaker, M. J. (Minouk J.), Schottker, B. (Ben), Sherman, M. E. (Mark E.), Shu, X.-O. (Xiao-Ou), Smichkoska, S. (Snezhana), Southey, M. C. (Melissa C.), Spinelli, J. J. (John J.), Swerdlow, A. J. (Anthony J.), Tamimi, R. M. (Rulla M.), Tapper, W. J. (William J.), Taylor, J. A. (Jack A.), Teras, L. R. (Lauren R.), Terry, M. B. (Mary Beth), Torres, D. (Diana), Troester, M. A. (Melissa A.), Vachon, C. M. (Celine M.), van Deurzen, C. H. (Carolien H. M.), van Veen, E. M. (Elke M.), Wagner, P. (Philippe), Weinberg, C. R. (Clarice R.), Wendt, C. (Camilla), Wesseling, J. (Jelle), Winqvist, R. (Robert), Wolk, A. (Alicja), Yang, X. R. (Xiaohong R.), Zheng, W. (Wei), Couch, F. J. (Fergus J.), Simard, J. (Jacques), Kraft, P. (Peter), Easton, D. F. (Douglas F.), Pharoah, P. D. (Paul D. P.), Schmidt, M. K. (Marjanka K.), Garcia-Closas, M. (Montserrat), Chatterjee, N. (Nilanjan), Ahearn, T. U. (Thomas U.), Zhang, H. (Haoyu), Michailidou, K. (Kyriaki), Milne, R. L. (Roger L.), Bolla, M. K. (Manjeet K.), Dennis, J. (Joe), Dunning, A. M. (Alison M.), Lush, M. (Michael), Wang, Q. (Qin), Andrulis, I. L. (Irene L.), Anton-Culver, H. (Hoda), Arndt, V. (Volker), Aronson, K. J. (Kristan J.), Auer, P. L. (Paul L.), Augustinsson, A. (Annelie), Baten, A. (Adinda), Becher, H. (Heiko), Behrens, S. (Sabine), Benitez, J. (Javier), Bermisheva, M. (Marina), Blomqvist, C. (Carl), Bojesen, S. E. (Stig E.), Bonanni, B. (Bernardo), Borresen-Dale, A.-L. (Anne-Lise), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Brooks-Wilson, A. (Angela), Bruening, T. (Thomas), Burwinkel, B. (Barbara), Buys, S. S. (Saundra S.), Canzian, F. (Federico), Castelao, J. E. (Jose E.), Chang-Claude, J. (Jenny), Chanock, S. J. (Stephen J.), Chenevix-Trench, G. (Georgia), Clarke, C. L. (Christine L.), Collee, J. M. (J. Margriet), Cox, A. (Angela), Cross, S. S. (Simon S.), Czene, K. (Kamila), Daly, M. B. (Mary B.), Devilee, P. (Peter), Dork, T. (Thilo), Dwek, M. (Miriam), Eccles, D. M. (Diana M.), Evans, D. G. (D. Gareth), Fasching, P. A. (Peter A.), Figueroa, J. (Jonine), Floris, G. (Giuseppe), Gago-Dominguez, M. (Manuela), Gapstur, S. M. (Susan M.), Garcia-Saenz, J. A. (Jose A.), Gaudet, M. M. (Mia M.), Giles, G. G. (Graham G.), Goldberg, M. S. (Mark S.), Gonzalez-Neira, A. (Anna), Alnaes, G. I. (Grethe I. Grenaker), Grip, M. (Mervi), Guenel, P. (Pascal), Haiman, C. A. (Christopher A.), Hall, P. (Per), Hamann, U. (Ute), Harkness, E. F. (Elaine F.), Heemskerk-Gerritsen, B. A. (Bernadette A. M.), Holleczek, B. (Bernd), Hollestelle, A. (Antoinette), Hooning, M. J. (Maartje J.), Hoover, R. N. (Robert N.), Hopper, J. L. (John L.), Howell, A. (Anthony), Jakimovska, M. (Milena), Jakubowska, A. (Anna), John, E. M. (Esther M.), Jones, M. E. (Michael E.), Jung, A. (Audrey), Kaaks, R. (Rudolf), Kauppila, S. (Saila), Keeman, R. (Renske), Khusnutdinova, E. (Elza), Kitahara, C. M. (Cari M.), Ko, Y.-D. (Yon-Dschun), Koutros, S. (Stella), Kristensen, V. N. (Vessela N.), Kruger, U. (Ute), Kubelka-Sabit, K. (Katerina), Kurian, A. W. (Allison W.), Kyriacou, K. (Kyriacos), Lambrechts, D. (Diether), Lee, D. G. (Derrick G.), Lindblom, A. (Annika), Linet, M. (Martha), Lissowska, J. (Jolanta), Llaneza, A. (Ana), Lo, W.-Y. (Wing-Yee), MacInnis, R. J. (Robert J.), Mannermaa, A. (Arto), Manoochehri, M. (Mehdi), Margolin, S. (Sara), Martinez, M. E. (Maria Elena), McLean, C. (Catriona), Meindl, A. (Alfons), Menon, U. (Usha), Nevanlinna, H. (Heli), Newman, W. G. (William G.), Nodora, J. (Jesse), Offit, K. (Kenneth), Olsson, H. (Hakan), Orr, N. (Nick), Park-Simon, T.-W. (Tjoung-Won), Patel, A. V. (Alpa, V), Peto, J. (Julian), Pita, G. (Guillermo), Plaseska-Karanfilska, D. (Dijana), Prentice, R. (Ross), Punie, K. (Kevin), Pylkas, K. (Katri), Radice, P. (Paolo), Rennert, G. (Gad), Romero, A. (Atocha), Ruediger, T. (Thomas), Saloustros, E. (Emmanouil), Sampson, S. (Sarah), Sandler, D. P. (Dale P.), Sawyer, E. J. (Elinor J.), Schmutzler, R. K. (Rita K.), Schoemaker, M. J. (Minouk J.), Schottker, B. (Ben), Sherman, M. E. (Mark E.), Shu, X.-O. (Xiao-Ou), Smichkoska, S. (Snezhana), Southey, M. C. (Melissa C.), Spinelli, J. J. (John J.), Swerdlow, A. J. (Anthony J.), Tamimi, R. M. (Rulla M.), Tapper, W. J. (William J.), Taylor, J. A. (Jack A.), Teras, L. R. (Lauren R.), Terry, M. B. (Mary Beth), Torres, D. (Diana), Troester, M. A. (Melissa A.), Vachon, C. M. (Celine M.), van Deurzen, C. H. (Carolien H. M.), van Veen, E. M. (Elke M.), Wagner, P. (Philippe), Weinberg, C. R. (Clarice R.), Wendt, C. (Camilla), Wesseling, J. (Jelle), Winqvist, R. (Robert), Wolk, A. (Alicja), Yang, X. R. (Xiaohong R.), Zheng, W. (Wei), Couch, F. J. (Fergus J.), Simard, J. (Jacques), Kraft, P. (Peter), Easton, D. F. (Douglas F.), Pharoah, P. D. (Paul D. P.), Schmidt, M. K. (Marjanka K.), Garcia-Closas, M. (Montserrat), and Chatterjee, N. (Nilanjan)
- Abstract
Background: Genome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear. Methods: Among 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes. Results: Eighty-five of 173 variants were associated with at least one tumor feature (false discovery rate < 5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at p < 0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions. Conclusion: This report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction.
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- 2022
17. Rare germline copy number variants (CNVs) and breast cancer risk
- Author
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Dennis, J. (Joe), Tyrer, J. P. (Jonathan P.), Walker, L. C. (Logan C.), Michailidou, K. (Kyriaki), Dorling, L. (Leila), Bolla, M. K. (Manjeet K.), Wang, Q. (Qin), Ahearn, T. U. (Thomas U.), Andrulis, I. L. (Irene L.), Anton-Culver, H. (Hoda), Antonenkova, N. N. (Natalia N.), Arndt, V. (Volker), Aronson, K. J. (Kristan J.), Freeman, L. E. (Laura E. Beane), Beckmann, M. W. (Matthias W.), Behrens, S. (Sabine), Benitez, J. (Javier), Bermisheva, M. (Marina), Bogdanova, N. V. (Natalia, V), Bojesen, S. E. (Stig E.), Brenner, H. (Hermann), Castelao, J. E. (Jose E.), Chang-Claude, J. (Jenny), Chenevix-Trench, G. (Georgia), Clarke, C. L. (Christine L.), N. C. (NBCS Collaborators), Collee, J. M. (J. Margriet), C. C. (CTS Consortium), Couch, F. J. (Fergus J.), Cox, A. (Angela), Cross, S. S. (Simon S.), Czene, K. (Kamila), Devilee, P. (Peter), Dörk, T. (Thilo), Dossus, L. (Laure), Eliassen, A. H. (A. Heather), Eriksson, M. (Mikael), Evans, D. G. (D. Gareth), Fasching, P. A. (Peter A.), Figueroa, J. (Jonine), Fletcher, O. (Olivia), Flyger, H. (Henrik), Fritschi, L. (Lin), Gabrielson, M. (Marike), Gago-Dominguez, M. (Manuela), Garcia-Closas, M. (Montserrat), Giles, G. G. (Graham G.), Gonzalez-Neira, A. (Anna), Guenel, P. (Pascal), Hahnen, E. (Eric), Haiman, C. A. (Christopher A.), Hall, P. (Per), Hollestelle, A. (Antoinette), Hoppe, R. (Reiner), Hopper, J. L. (John L.), Howell, A. (Anthony), A. I. (ABCTB Investigators), k. I. (kConFab/AOCS Investigators), Jager, A. (Agnes), Jakubowska, A. (Anna), John, E. M. (Esther M.), Johnson, N. (Nichola), Jones, M. E. (Michael E.), Jung, A. (Audrey), Kaaks, R. (Rudolf), Keeman, R. (Renske), Khusnutdinova, E. (Elza), Kitahara, C. M. (Cari M.), Ko, Y.-D. (Yon-Dschun), Kosma, V.-M. (Veli-Matti), Koutros, S. (Stella), Kraft, P. (Peter), Kristensen, V. N. (Vessela N.), Kubelka-Sabit, K. (Katerina), Kurian, A. W. (Allison W.), Lacey, J. V. (James, V), Lambrechts, D. (Diether), Larson, N. L. (Nicole L.), Linet, M. (Martha), Ogrodniczak, A. (Alicja), Mannermaa, A. (Arto), Manoukian, S. (Siranoush), Margolin, S. (Sara), Mavroudis, D. (Dimitrios), Milne, R. L. (Roger L.), Muranen, T. A. (Taru A.), Murphy, R. A. (Rachel A.), Nevanlinna, H. (Heli), Olson, J. E. (Janet E.), Olsson, H. (Hakan), Park-Simon, T.-W. (Tjoung-Won), Perou, C. M. (Charles M.), Peterlongo, P. (Paolo), Plaseska-Karanfilska, D. (Dijana), Pylkas, K. (Katri), Rennert, G. (Gad), Saloustros, E. (Emmanouil), Sandler, D. P. (Dale P.), Sawyer, E. J. (Elinor J.), Schmidt, M. K. (Marjanka K.), Schmutzler, R. K. (Rita K.), Shibli, R. (Rana), Smeets, A. (Ann), Soucy, P. (Penny), Southey, M. C. (Melissa C.), Swerdlow, A. J. (Anthony J.), Tamimi, R. M. (Rulla M.), Taylor, J. A. (Jack A.), Teras, L. R. (Lauren R.), Terry, M. B. (Mary Beth), Tomlinson, I. (Ian), Troester, M. A. (Melissa A.), Truong, T. (Therese), Vachon, C. M. (Celine M.), Wendt, C. (Camilla), Winqvist, R. (Robert), Wolk, A. (Alicja), Yang, X. R. (Xiaohong R.), Zheng, W. (Wei), Ziogas, A. (Argyrios), Simard, J. (Jacques), Dunning, A. M. (Alison M.), Pharoah, P. D. (Paul D. P.), Easton, D. F. (Douglas F.), Dennis, J. (Joe), Tyrer, J. P. (Jonathan P.), Walker, L. C. (Logan C.), Michailidou, K. (Kyriaki), Dorling, L. (Leila), Bolla, M. K. (Manjeet K.), Wang, Q. (Qin), Ahearn, T. U. (Thomas U.), Andrulis, I. L. (Irene L.), Anton-Culver, H. (Hoda), Antonenkova, N. N. (Natalia N.), Arndt, V. (Volker), Aronson, K. J. (Kristan J.), Freeman, L. E. (Laura E. Beane), Beckmann, M. W. (Matthias W.), Behrens, S. (Sabine), Benitez, J. (Javier), Bermisheva, M. (Marina), Bogdanova, N. V. (Natalia, V), Bojesen, S. E. (Stig E.), Brenner, H. (Hermann), Castelao, J. E. (Jose E.), Chang-Claude, J. (Jenny), Chenevix-Trench, G. (Georgia), Clarke, C. L. (Christine L.), N. C. (NBCS Collaborators), Collee, J. M. (J. Margriet), C. C. (CTS Consortium), Couch, F. J. (Fergus J.), Cox, A. (Angela), Cross, S. S. (Simon S.), Czene, K. (Kamila), Devilee, P. (Peter), Dörk, T. (Thilo), Dossus, L. (Laure), Eliassen, A. H. (A. Heather), Eriksson, M. (Mikael), Evans, D. G. (D. Gareth), Fasching, P. A. (Peter A.), Figueroa, J. (Jonine), Fletcher, O. (Olivia), Flyger, H. (Henrik), Fritschi, L. (Lin), Gabrielson, M. (Marike), Gago-Dominguez, M. (Manuela), Garcia-Closas, M. (Montserrat), Giles, G. G. (Graham G.), Gonzalez-Neira, A. (Anna), Guenel, P. (Pascal), Hahnen, E. (Eric), Haiman, C. A. (Christopher A.), Hall, P. (Per), Hollestelle, A. (Antoinette), Hoppe, R. (Reiner), Hopper, J. L. (John L.), Howell, A. (Anthony), A. I. (ABCTB Investigators), k. I. (kConFab/AOCS Investigators), Jager, A. (Agnes), Jakubowska, A. (Anna), John, E. M. (Esther M.), Johnson, N. (Nichola), Jones, M. E. (Michael E.), Jung, A. (Audrey), Kaaks, R. (Rudolf), Keeman, R. (Renske), Khusnutdinova, E. (Elza), Kitahara, C. M. (Cari M.), Ko, Y.-D. (Yon-Dschun), Kosma, V.-M. (Veli-Matti), Koutros, S. (Stella), Kraft, P. (Peter), Kristensen, V. N. (Vessela N.), Kubelka-Sabit, K. (Katerina), Kurian, A. W. (Allison W.), Lacey, J. V. (James, V), Lambrechts, D. (Diether), Larson, N. L. (Nicole L.), Linet, M. (Martha), Ogrodniczak, A. (Alicja), Mannermaa, A. (Arto), Manoukian, S. (Siranoush), Margolin, S. (Sara), Mavroudis, D. (Dimitrios), Milne, R. L. (Roger L.), Muranen, T. A. (Taru A.), Murphy, R. A. (Rachel A.), Nevanlinna, H. (Heli), Olson, J. E. (Janet E.), Olsson, H. (Hakan), Park-Simon, T.-W. (Tjoung-Won), Perou, C. M. (Charles M.), Peterlongo, P. (Paolo), Plaseska-Karanfilska, D. (Dijana), Pylkas, K. (Katri), Rennert, G. (Gad), Saloustros, E. (Emmanouil), Sandler, D. P. (Dale P.), Sawyer, E. J. (Elinor J.), Schmidt, M. K. (Marjanka K.), Schmutzler, R. K. (Rita K.), Shibli, R. (Rana), Smeets, A. (Ann), Soucy, P. (Penny), Southey, M. C. (Melissa C.), Swerdlow, A. J. (Anthony J.), Tamimi, R. M. (Rulla M.), Taylor, J. A. (Jack A.), Teras, L. R. (Lauren R.), Terry, M. B. (Mary Beth), Tomlinson, I. (Ian), Troester, M. A. (Melissa A.), Truong, T. (Therese), Vachon, C. M. (Celine M.), Wendt, C. (Camilla), Winqvist, R. (Robert), Wolk, A. (Alicja), Yang, X. R. (Xiaohong R.), Zheng, W. (Wei), Ziogas, A. (Argyrios), Simard, J. (Jacques), Dunning, A. M. (Alison M.), Pharoah, P. D. (Paul D. P.), and Easton, D. F. (Douglas F.)
- Abstract
Germline copy number variants (CNVs) are pervasive in the human genome but potential disease associations with rare CNVs have not been comprehensively assessed in large datasets. We analysed rare CNVs in genes and non-coding regions for 86,788 breast cancer cases and 76,122 controls of European ancestry with genome-wide array data. Gene burden tests detected the strongest association for deletions in BRCA1 (P = 3.7E-18). Nine other genes were associated with a p-value < 0.01 including known susceptibility genes CHEK2 (P = 0.0008), ATM (P = 0.002) and BRCA2 (P = 0.008). Outside the known genes we detected associations with p-values < 0.001 for either overall or subtype-specific breast cancer at nine deletion regions and four duplication regions. Three of the deletion regions were in established common susceptibility loci. To the best of our knowledge, this is the first genome-wide analysis of rare CNVs in a large breast cancer case-control dataset. We detected associations with exonic deletions in established breast cancer susceptibility genes. We also detected suggestive associations with non-coding CNVs in known and novel loci with large effects sizes. Larger sample sizes will be required to reach robust levels of statistical significance.
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- 2022
18. Iam hiQ—a novel pair of accuracy indices for imputed genotypes
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Rosenberger, A., Tozzi, V., Bickeböller, H., Hung, R.J., Christiani, D.C., Caporaso, N.E., Liu, G., Bojesen, S.E., Le Marchand, L., Albanes, D., Aldrich, M.C., Tardon, A., Fernández-Tardón, G., Rennert, G., Field, J.K., Davies, M., Liloglou, T., Kiemeney, L.A., Lazarus, P., Haugen, A., Zienolddiny, S., Lam, S., Schabath, M.B., Andrew, A.S., Duell, E.J., Arnold, S.M., Brunnström, H., Melander, O., Goodman, G.E., Chen, C., Doherty, J.A., Teare, M.D., Cox, A., Woll, P.J., Risch, A., Muley, T.R., Johansson, M., Brennan, P., Landi, M.T., Shete, S.S., and Amos, C.I.
- Abstract
Background\ud \ud Imputation of untyped markers is a standard tool in genome-wide association studies to close the gap between directly genotyped and other known DNA variants. However, high accuracy with which genotypes are imputed is fundamental. Several accuracy measures have been proposed and some are implemented in imputation software, unfortunately diversely across platforms. In the present paper, we introduce Iam hiQ, an independent pair of accuracy measures that can be applied to dosage files, the output of all imputation software. Iam (imputation accuracy measure) quantifies the average amount of individual-specific versus population-specific genotype information in a linear manner. hiQ (heterogeneity in quantities of dosages) addresses the inter-individual heterogeneity between dosages of a marker across the sample at hand.\ud \ud \ud \ud Results\ud \ud Applying both measures to a large case–control sample of the International Lung Cancer Consortium (ILCCO), comprising 27,065 individuals, we found meaningful thresholds for Iam and hiQ suitable to classify markers of poor accuracy. We demonstrate how Manhattan-like plots and moving averages of Iam and hiQ can be useful to identify regions enriched with less accurate imputed markers, whereas these regions would by missed when applying the accuracy measure info (implemented in IMPUTE2).\ud \ud \ud \ud Conclusion\ud \ud We recommend using Iam hiQ additional to other accuracy scores for variant filtering before stepping into the analysis of imputed GWAS data.
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- 2022
19. Smoking Attenuates the Negative Association between Carotenoids Consumption and Colorectal Cancer Risk
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Chaiter, Y., Gruber, S. B., Ben-Amotz, A., Almog, R., Rennert, H. S., Fischler, R., Rozen, G., and Rennert, G.
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- 2009
- Full Text
- View/download PDF
20. Double heterozygosity in the BRCA1 and BRCA2 genes in the Jewish population
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Lavie, O., Narod, S., Lejbkowicz, F., Dishon, S., Goldberg, Y., Gemer, O., and Rennert, G.
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- 2011
- Full Text
- View/download PDF
21. Artificial intelligence for detection of microsatellite instability in colorectal cancer-a multicentric analysis of a pre-screening tool for clinical application
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Echle, A, Ghaffari Laleh, N, Quirke, P, Grabsch, H I, Muti, H S, Saldanha, O L, Brockmoeller, S F, van den Brandt, P A, Hutchins, G G A, Richman, S D, Horisberger, K, Galata, C, Ebert, M P, Eckardt, M, Boutros, M, Horst, D, Reissfelder, C, Alwers, E, Brinker, T J, Langer, R, Jenniskens, J C A, Offermans, K, Mueller, W, Gray, R, Gruber, S B, Greenson, J K, Rennert, G, Bonner, J D, Schmolze, D, Chang-Claude, J, Brenner, H, Trautwein, C, Boor, P, Jaeger, D, Gaisa, N T, Hoffmeister, M, West, N P, Kather, J N, Pathologie, RS: GROW - R2 - Basic and Translational Cancer Biology, Epidemiologie, RS: GROW - R1 - Prevention, and RS: CAPHRI - R5 - Optimising Patient Care
- Subjects
RISK ,Cancer Research ,PREDICTION ,deep learning ,colorectal cancer ,610 Medicine & health ,DNA Mismatch Repair ,digestive system diseases ,MODEL ,Lynch syndrome ,Oncology ,Artificial Intelligence ,biomarker ,570 Life sciences ,biology ,Humans ,Microsatellite Instability ,Colorectal Neoplasms ,Early Detection of Cancer - Abstract
ESMO open 7(2), 100400 (2022). doi:10.1016/j.esmoop.2022.100400, Published by BMJ, London
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- 2021
22. Differences in the characteristics of families with BRCA1 and BRCA2 mutations in Israel
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Rennert, G, Dishon, S, Rennert, H S, and Fares, F
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- 2005
23. Cancer Genetics Service Provision : A Comparison of Seven European Centres
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Hopwood, P., van Asperen, C.J., Borreani, G., Bourret, P., Decruyenaere, M., Dishon, S., Eisinger, F., Evans, D.G.R., Evers-Kiebooms, G., Gangeri, L., Hagoel, L., Legius, E., Nippert, I., Rennert, G., Schlegelberger, B., Sevilla, C., Sobol, H., Tibben, A., Welkenhuysen, M., and Julian-Reynier, C.
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- 2003
24. Functional annotation of the 2q35 breast cancer risk locus implicates a structural variant in influencing activity of a long-range enhancer element
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Baxter, J.S., Johnson, N., Tomczyk, K., Gillespie, A., Maguire, S., Brough, R., Fachal, L., Michailidou, K., Bolla, M.K., Wang, Q., Dennis, J., Ahearn, T.U., Andrulis, I.L., Anton-Culver, H., Antonenkova, N.N., Arndt, V., Aronson, K.J., Augustinsson, A., Becher, H., Beckmann, M.W., Behrens, S., Benitez, J., Bermisheva, M., Bogdanova, N.V., Bojesen, S.E., Brenner, H., Brucker, S.Y., Cai, Q.Y., Campa, D., Canzian, F., Castelao, J.E., Chan, T.L., Chang-Claude, J., Chanock, S.J., Chenevix-Trench, G., Choi, J.Y., Clarke, C.L., Collaborators, N., Colonna, S., Conroy, D.M., Couch, F.J., Cox, A., Cross, S.S., Czene, K., Daly, M.B., Devilee, P., Dork, T., Dossus, L., Dwek, M., Eccles, D.M., Ekici, A.B., Eliassen, A.H., Engel, C., Fasching, P.A., Figueroa, J., Flyger, H., Gago-Dominguez, M., Gao, C., Garcia-Closas, M., Garcia-Saenz, J.A., Ghoussaini, M., Giles, G.G., Goldberg, M.S., Gonzalez-Neira, A., Guenel, P., Gundert, M., Haeberle, L., Hahnen, E., Haiman, C.A., Hall, P., Hamann, U., Hartman, M., Hatse, S., Hauke, J., Hollestelle, A., Hoppe, R., Hopper, J.L., Hou, M.F., Ito, H., Iwasaki, M., Jager, A., Jakubowska, A., Janni, W., John, E.M., Joseph, V., Jung, A., Kaaks, R., Kang, D., Keeman, R., Khusnutdinova, E., Kim, S.W., Kosma, V.M., Kraft, P., Kristensen, V.N., Kubelka-Sabit, K., Kurian, A.W., Kwong, A., Lacey, J.V., Lambrechts, D., Larson, N.L., Larsson, S.C., Marchand, L. le, Lejbkowicz, F., Li, J.M., Long, J.R., Lophatananon, A., LubiNski, J., Mannermaa, A., Manoochehri, M., Manoukian, S., Margolin, S., Matsuo, K., Mavroudis, D., Mayes, R., Menon, U., Milne, R.L., Taib, N.A.M., Muir, K., Muranen, T.A., Murphy, R.A., Nevanlinna, H., O'Brien, K.M., Offit, K., Olson, J.E., Olsson, H., Park, S.K., Park-Simon, T.W., Patel, A.V., Peterlongo, P., Peto, J., Plaseska-Karanfilska, D., Presneau, N., Pylkas, K., Rack, B., Rennert, G., Romero, A., Ruebner, M., Rudiger, T., Saloustros, E., Sandler, D.P., Sawyer, E.J., Schmidt, M.K., Schmutzler, R.K., Schneeweiss, A., Schoemaker, M.J., Shah, M., Shen, C.Y., Shu, X.O., Simard, J., Southey, M.C., Stone, J., Surowy, H., Swerdlow, A.J., Tamimi, R.M., Tapper, W.J., Taylor, J.A., Teo, S.H., Teras, L.R., Terry, M.B., Toland, A.E., Tomlinson, I., Truong, T., Tseng, C.C., Untch, M., Vachon, C.M., Ouweland, A.M.W. van den, Wang, S.S., Weinberg, C.R., Wendt, C., Winham, S.J., Winqvist, R., Wolk, A., Wu, A.H., Yamaji, T., Zheng, W., Ziogas, A., Pharoah, P.D.P., Dunning, A.M., Easton, D.F., Pettitt, S.J., Lord, C.J., Haider, S., Orr, N., Fletcher, O., kConFab Investigators, ABCTB Investigators, Medical Oncology, Clinical Genetics, HUS Gynecology and Obstetrics, Department of Obstetrics and Gynecology, Biosciences, Dennis, Joe [0000-0003-4591-1214], Pharoah, Paul [0000-0001-8494-732X], Dunning, Alison [0000-0001-6651-7166], Easton, Douglas [0000-0003-2444-3247], and Apollo - University of Cambridge Repository
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Basic medicine ,breast cancer risk ,0302 clinical medicine ,Transcription (biology) ,Risk Factors ,WIDE ASSOCIATION ,TRANSCRIPTION ,Promoter Regions, Genetic ,Genetics (clinical) ,Sequence Deletion ,Genetics ,Genetics & Heredity ,0303 health sciences ,Chromosome Mapping ,3. Good health ,030220 oncology & carcinogenesis ,Chromosomes, Human, Pair 2 ,Pair 2 ,Female ,Medical Genetics ,Life Sciences & Biomedicine ,Human ,Tumor suppressor gene ,SUSCEPTIBILITY LOCI ,In silico ,3122 Cancers ,Locus (genetics) ,Breast Neoplasms ,Biology ,Chromosomes ,Article ,Cell Line ,RNAS ,Promoter Regions ,03 medical and health sciences ,functional annotation ,risk locus ,CRISPR-Cas Systems ,Genetic Association Studies ,Genetic Variation ,Humans ,Insulin-Like Growth Factor Binding Protein 5 ,Molecular Sequence Annotation ,11Q13 ,Genetic ,SDG 3 - Good Health and Well-being ,Enhancer ,Transcription factor ,030304 developmental biology ,Medicinsk genetik ,Reporter gene ,Science & Technology ,IDENTIFICATION ,Clinical medicine ,Estrogen receptor alpha - Abstract
A combination of genetic and functional approaches has identified three independent breast cancer risk loci at 2q35. A recent fine-scale mapping analysis to refine these associations resulted in 1 (signal 1), 5 (signal 2), and 42 (signal 3) credible causal variants at these loci. We used publicly available in silico DNase I and ChIP-seq data with in vitro reporter gene and CRISPR assays to annotate signals 2 and 3. We identified putative regulatory elements that enhanced cell-type-specific transcription from the IGFBP5 promoter at both signals (30- to 40-fold increased expression by the putative regulatory element at signal 2, 2- to 3-fold by the putative regulatory element at signal 3). We further identified one of the five credible causal variants at signal 2, a 1.4 kb deletion (esv3594306), as the likely causal variant; the deletion allele of this variant was associated with an average additional increase in IGFBP5 expression of 1.3-fold (MCF-7) and 2.2-fold (T-47D). We propose a model in which the deletion allele of esv3594306 juxtaposes two transcription factor binding regions (annotated by estrogen receptor alpha ChIP-seq peaks) to generate a single extended regulatory element. This regulatory element increases cell-type-specific expression of the tumor suppressor gene IGFBP5 and, thereby, reduces risk of estrogen receptor-positive breast cancer (odds ratio = 0.77, 95% CI 0.74-0.81, p = 3.1 × 10-31). ispartof: AMERICAN JOURNAL OF HUMAN GENETICS vol:108 issue:7 pages:1190-1203 ispartof: location:United States status: published
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- 2021
25. Dietary intervention studies and cancer prevention
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Rennert, G
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- 2002
26. Screening with faecal occult blood test (FOBT) for colorectal cancer: assessment of two methods that attempt to improve compliance
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Ore, L, Hagoel, L, Lavi, I, and Rennert, G
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- 2001
27. Breast cancer screening in 21 countries: delivery of services, notification of results and outcomes ascertainment
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Ballard-Barbash, R, Klabunde, C, Paci, E, Broeders, M, Coleman, E A, Fracheboud, J, Bouchard, F, Rennert, G, and Shapiro, S
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- 1999
28. Lung Cancer in Israel, 1962-1982: II. Ethnic Differences among Jews
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Rennert, G., Rennert, H. S., Katz, L., and Epstein, L.
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- 1990
29. Lung Cancer Histology in Major Ethnic Groups among the Jews. Israel, 1962-1982
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Rennert, G., Rennert, H. S., and Epstein, L.
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- 1991
30. Establishing an International Computer Network for Research and Teaching in Public Health and Epidemiology
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Østbye, T., Bojan, F., Rennert, G., Hurlen, P., and Garner, B.
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- 1991
31. Lung Cancer in Israel, 1962-1982: I. Jews and Arabs
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Rennert, G., Tamir, A., Katz, L., Steinitz, R., and Epstein, L.
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- 1988
32. O-023 Observational data outcomes of chemotherapy backbone for MSI – high metastatic colorectal cancer in molecular epidemiology of colorectal cancer in Israel
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Shulman, K., Barnett-Griness, O., Friedman, V., Gruber Stephen, B., Lejbkowicz, F., and Rennert, G.
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- 2016
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33. The relationship between obesity and the increase in serum 25(OH)D levels in response to vitamin D supplementation
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Saliba, W., Barnett-Griness, O., and Rennert, G.
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- 2013
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34. CYP3A7*1C allele:linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers
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Johnson, N. (Nichola), Maguire, S. (Sarah), Morra, A. (Anna), Kapoor, P. M. (Pooja Middha), Tomczyk, K. (Katarzyna), Jones, M. E. (Michael E.), Schoemaker, M. J. (Minouk J.), Gilham, C. (Clare), Bolla, M. K. (Manjeet K.), Wang, Q. (Qin), Dennis, J. (Joe), Ahearn, T. U. (Thomas U.), Andrulis, I. L. (Irene L.), Anton-Culver, H. (Hoda), Antonenkova, N. N. (Natalia N.), Arndt, V. (Volker), Aronson, K. J. (Kristan J.), Augustinsson, A. (Annelie), Baynes, C. (Caroline), Freeman, L. E. (Laura E. Beane), Beckmann, M. W. (Matthias W.), Benitez, J. (Javier), Bermisheva, M. (Marina), Blomqvist, C. (Carl), Boeckx, B. (Bram), Bogdanova, N. V. (Natalia V.), Bojesen, S. E. (Stig E.), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Burwinkel, B. (Barbara), Campa, D. (Daniele), Canzian, F. (Federico), Castelao, J. E. (Jose E.), Chanock, S. J. (Stephen J.), Chenevix-Trench, G. (Georgia), Clarke, C. L. (Christine L.), Conroy, D. M. (Don M.), Couch, F. J. (Fergus J.), Cox, A. (Angela), Cross, S. S. (Simon S.), Czene, K. (Kamila), Doerk, T. (Thilo), Eliassen, A. H. (A. Heather), Engel, C. (Christoph), Evans, D. G. (D. Gareth), Fasching, P. A. (Peter A.), Figueroa, J. (Jonine), Floris, G. (Giuseppe), Flyger, H. (Henrik), Gago-Dominguez, M. (Manuela), Gapstur, S. M. (Susan M.), Garcia-Closas, M. (Montserrat), Gaudet, M. M. (Mia M.), Giles, G. G. (Graham G.), Goldberg, M. S. (Mark S.), Gonzalez-Neira, A. (Anna), Guenel, P. (Pascal), Hahnen, E. (Eric), Haiman, C. A. (Christopher A.), Hakansson, N. (Niclas), Hall, P. (Per), Hamann, U. (Ute), Harrington, P. A. (Patricia A.), Hart, S. N. (Steven N.), Hooning, M. J. (Maartje J.), Hopper, J. L. (John L.), Howell, A. (Anthony), Hunter, D. J. (David J.), Jager, A. (Agnes), Jakubowska, A. (Anna), John, E. M. (Esther M.), Kaaks, R. (Rudolf), Keeman, R. (Renske), Khusnutdinova, E. (Elza), Kitahara, C. M. (Cari M.), Kosma, V.-M. (Veli-Matti), Koutros, S. (Stella), Kraft, P. (Peter), Kristensen, V. N. (Vessela N.), Kurian, A. W. (Allison W.), Lambrechts, D. (Diether), Le Marchand, L. (Loic), Linet, M. (Martha), Lubinski, J. (Jan), Mannermaa, A. (Arto), Manoukian, S. (Siranoush), Margolin, S. (Sara), Martens, J. W. (John W. M.), Mavroudis, D. (Dimitrios), Mayes, R. (Rebecca), Meindl, A. (Alfons), Milne, R. L. (Roger L.), Neuhausen, S. L. (Susan L.), Nevanlinna, H. (Heli), Newman, W. G. (William G.), Nielsen, S. F. (Sune F.), Nordestgaard, B. G. (Borge G.), Obi, N. (Nadia), Olshan, A. F. (Andrew F.), Olson, J. E. (Janet E.), Olsson, H. (Hakan), Orban, E. (Ester), Park-Simon, T.-W. (Tjoung-Won), Peterlongo, P. (Paolo), Plaseska-Karanfilska, D. (Dijana), Pylkäs, K. (Katri), Rennert, G. (Gad), Rennert, H. S. (Hedy S.), Ruddy, K. J. (Kathryn J.), Saloustros, E. (Emmanouil), Sandler, D. P. (Dale P.), Sawyer, E. J. (Elinor J.), Schmutzler, R. K. (Rita K.), Scott, C. (Christopher), Shu, X.-O. (Xiao-Ou), Simard, J. (Jacques), Smichkoska, S. (Snezhana), Sohn, C. (Christof), Southey, M. C. (Melissa C.), Spinelli, J. J. (John J.), Stone, J. (Jennifer), Tamimi, R. M. (Rulla M.), Taylor, J. A. (Jack A.), Tollenaar, R. A. (Rob A. E. M.), Tomlinson, I. (Ian), Troester, M. A. (Melissa A.), Truong, T. (Therese), Vachon, C. M. (Celine M.), van Veen, E. M. (Elke M.), Wang, S. S. (Sophia S.), Weinberg, C. R. (Clarice R.), Wendt, C. (Camilla), Wildiers, H. (Hans), Winqvist, R. (Robert), Wolk, A. (Alicja), Zheng, W. (Wei), Ziogas, A. (Argyrios), Dunning, A. M. (Alison M.), Pharoah, P. D. (Paul D. P.), Easton, D. F. (Douglas F.), Howie, A. F. (A. Forbes), Peto, J. (Julian), dos-Santos-Silva, I. (Isabel), Swerdlow, A. J. (Anthony J.), Chang-Claude, J. (Jenny), Schmidt, M. K. (Marjanka K.), Orr, N. (Nick), and Fletcher, O. (Olivia)
- Abstract
Background: Epidemiological studies provide strong evidence for a role of endogenous sex hormones in the aetiology of breast cancer. The aim of this analysis was to identify genetic variants that are associated with urinary sex-hormone levels and breast cancer risk. Methods: We carried out a genome-wide association study of urinary oestrone-3-glucuronide and pregnanediol-3-glucuronide levels in 560 premenopausal women, with additional analysis of progesterone levels in 298 premenopausal women. To test for the association with breast cancer risk, we carried out follow-up genotyping in 90,916 cases and 89,893 controls from the Breast Cancer Association Consortium. All women were of European ancestry. Results: For pregnanediol-3-glucuronide, there were no genome-wide significant associations; for oestrone-3-glucuronide, we identified a single peak mapping to the CYP3A locus, annotated by rs45446698. The minor rs45446698-C allele was associated with lower oestrone-3-glucuronide (−49.2%, 95% CI −56.1% to −41.1%, P = 3.1 × 10⁻¹⁸); in follow-up analyses, rs45446698-C was also associated with lower progesterone (−26.7%, 95% CI −39.4% to −11.6%, P = 0.001) and reduced risk of oestrogen and progesterone receptor-positive breast cancer (OR = 0.86, 95% CI 0.82–0.91, P = 6.9 × 10⁻¹⁸). Conclusions: The CYP3A7*1C allele is associated with reduced risk of hormone receptor-positive breast cancer possibly mediated via an effect on the metabolism of endogenous sex hormones in premenopausal women.
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- 2021
35. Mendelian randomisation study of smoking exposure in relation to breast cancer risk
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Park, HA, Neumeyer, S, Michailidou, K, Bolla, MK, Wang, Q, Dennis, J, Ahearn, TU, Andrulis, IL, Anton-Culver, H, Antonenkova, NN, Arndt, V, Aronson, KJ, Augustinsson, A, Baten, A, Beane Freeman, LE, Becher, H, Beckmann, MW, Behrens, S, Benitez, J, Bermisheva, M, Bogdanova, NV, Bojesen, SE, Brauch, H, Brenner, H, Brucker, SY, Burwinkel, B, Campa, D, Canzian, F, Castelao, JE, Chanock, SJ, Chenevix-Trench, G, Clarke, CL, Børresen-Dale, A-L, Grenaker Alnæs, GI, Sahlberg, KK, Ottestad, L, Kåresen, R, Schlichting, E, Holmen, MM, Sauer, T, Haakensen, V, Engebråten, O, Naume, B, Fosså, A, Kiserud, CE, Reinertsen, KV, Helland, Å, Riis, M, Geisler, J, Conroy, DM, Couch, FJ, Cox, A, Cross, SS, Czene, K, Daly, MB, Devilee, P, Dörk, T, dos-Santos-Silva, I, Dwek, M, Eccles, DM, Eliassen, AH, Engel, C, Eriksson, M, Evans, DG, Fasching, PA, Flyger, H, Fritschi, L, García-Closas, M, García-Sáenz, JA, Gaudet, MM, Giles, GG, Glendon, G, Goldberg, MS, Goldgar, DE, González-Neira, A, Grip, M, Guénel, P, Hahnen, E, Haiman, CA, Håkansson, N, Hall, P, Hamann, U, Han, S, Harkness, EF, Hart, SN, He, W, Heemskerk-Gerritsen, BAM, Hopper, JL, Hunter, DJ, Clarke, C, Marsh, D, Scott, R, Baxter, R, Yip, D, Carpenter, J, Davis, A, Pathmanathan, N, Simpson, P, Graham, D, Sachchithananthan, M, Amor, D, Andrews, L, Antill, Y, Balleine, R, Beesley, J, Bennett, I, Bogwitz, M, Botes, L, Brennan, M, Brown, M, Buckley, M, Burke, J, Butow, P, Caldon, L, Campbell, I, Chauhan, D, Chauhan, M, Christian, A, Cohen, P, Colley, A, Crook, A, Cui, J, Cummings, M, Dawson, S-J, DeFazio, A, Delatycki, M, Dickson, R, Dixon, J, Edkins, T, Edwards, S, Farshid, G, Fellows, A, Fenton, G, Field, M, Flanagan, J, Fong, P, Forrest, L, Fox, S, French, J, Friedlander, M, Gaff, C, Gattas, M, George, P, Greening, S, Harris, M, Hart, S, Hayward, N, Hopper, J, Hoskins, C, Hunt, C, James, P, Jenkins, M, Kidd, A, Kirk, J, Koehler, J, Kollias, J, Lakhani, S, Lawrence, M, Lindeman, G, Lipton, L, Lobb, L, Mann, G, McLachlan, SA, Meiser, B, Milne, R, Nightingale, S, O’Connell, S, O’Sullivan, S, Ortega, DG, Pachter, N, Patterson, B, Pearn, A, Phillips, K, Pieper, E, Rickard, E, Robinson, B, Saleh, M, Salisbury, E, Saunders, C, Saunus, J, Scott, C, Sexton, A, Shelling, A, Southey, M, Spurdle, A, Taylor, J, Taylor, R, Thorne, H, Trainer, A, Tucker, K, Visvader, J, Walker, L, Williams, R, Winship, I, Young, MA, Jager, A, Jakubowska, A, John, EM, Jung, A, Kaaks, R, Kapoor, PM, Keeman, R, Khusnutdinova, E, Kitahara, CM, Koppert, LB, Koutros, S, Kristensen, VN, Kurian, AW, Lacey, J, Lambrechts, D, Le Marchand, L, Lo, W-Y, Lubiński, J, Mannermaa, A, Manoochehri, M, Margolin, S, Martinez, ME, Mavroudis, D, Meindl, A, Menon, U, Milne, RL, Muranen, TA, Nevanlinna, H, Newman, WG, Nordestgaard, BG, Offit, K, Olshan, AF, Olsson, H, Park-Simon, T-W, Peterlongo, P, Peto, J, Plaseska-Karanfilska, D, Presneau, N, Radice, P, Rennert, G, Rennert, HS, Romero, A, Saloustros, E, Sawyer, EJ, Schmidt, MK, Schmutzler, RK, Schoemaker, MJ, Schwentner, L, Shah, M, Shu, X-O, Simard, J, Smeets, A, Southey, MC, Spinelli, JJ, Stevens, V, Swerdlow, AJ, Tamimi, RM, Tapper, WJ, Taylor, JA, Terry, MB, Tomlinson, I, Troester, MA, Truong, T, Vachon, CM, van Veen, EM, Vijai, J, Wang, S, Wendt, C, Winqvist, R, Wolk, A, Ziogas, A, Dunning, AM, Pharoah, PDP, Easton, DF, Zheng, W, Kraft, P, Chang-Claude, J, HUS Gynecology and Obstetrics, Department of Obstetrics and Gynecology, Park, Hanla A. [0000-0001-8055-3729], Dennis, Joe [0000-0003-4591-1214], Augustinsson, Annelie [0000-0003-3415-0536], Brenner, Hermann [0000-0002-6129-1572], Canzian, Federico [0000-0002-4261-4583], Cox, Angela [0000-0002-5138-1099], Devilee, Peter [0000-0002-8023-2009], Fasching, Peter A. [0000-0003-4885-8471], Harkness, Elaine F. [0000-0001-6625-7739], Hart, Steven N. [0000-0001-7714-2734], Heemskerk-Gerritsen, Bernadette A. M. [0000-0002-9724-6693], Jakubowska, Anna [0000-0002-5650-0501], Kapoor, Pooja Middha [0000-0001-5503-8215], Kurian, Allison W. [0000-0002-6175-9470], Newman, William G. [0000-0002-6382-4678], Peterlongo, Paolo [0000-0001-6951-6855], Peto, Julian [0000-0002-1685-8912], Sawyer, Elinor J. [0000-0001-8285-4111], Scott, Christopher [0000-0003-1340-0647], Smeets, Ann [0000-0002-5091-6602], Tomlinson, Ian [0000-0003-3037-1470], Truong, Thérèse [0000-0002-2943-6786], Pharoah, Paul D. P. [0000-0001-8494-732X], and Apollo - University of Cambridge Repository
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0301 basic medicine ,Oncology ,Medicin och hälsovetenskap ,Cancer Research ,Genotyping Techniques ,Breast Neoplasms ,Case-Control Studies ,Cigarette Smoking ,Female ,Genetic Pleiotropy ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Humans ,Mendelian Randomization Analysis ,Polymorphism, Single Nucleotide ,ALCOHOL ,Medical and Health Sciences ,0302 clinical medicine ,Breast cancer ,Pleiotropy ,Epidemiology ,Medicine ,TOBACCO ,Breast Neoplasms/epidemiology ,Cigarette Smoking/adverse effects ,WOMEN ,ASSOCIATION ,Single Nucleotide ,3. Good health ,Substance abuse ,692/699/67/1347 ,030220 oncology & carcinogenesis ,Life Sciences & Biomedicine ,692/499 ,medicine.medical_specialty ,3122 Cancers ,Single-nucleotide polymorphism ,Article ,03 medical and health sciences ,Internal medicine ,ddc:610 ,Polymorphism ,Genetic association ,Science & Technology ,business.industry ,Cancer ,medicine.disease ,030104 developmental biology ,Clinical research ,Risk factors ,TISSUE ,INFERENCE ,CIGARETTE-SMOKING ,business - Abstract
Background Despite a modest association between tobacco smoking and breast cancer risk reported by recent epidemiological studies, it is still equivocal whether smoking is causally related to breast cancer risk. Methods We applied Mendelian randomisation (MR) to evaluate a potential causal effect of cigarette smoking on breast cancer risk. Both individual-level data as well as summary statistics for 164 single-nucleotide polymorphisms (SNPs) reported in genome-wide association studies of lifetime smoking index (LSI) or cigarette per day (CPD) were used to obtain MR effect estimates. Data from 108,420 invasive breast cancer cases and 87,681 controls were used for the LSI analysis and for the CPD analysis conducted among ever-smokers from 26,147 cancer cases and 26,072 controls. Sensitivity analyses were conducted to address pleiotropy. Results Genetically predicted LSI was associated with increased breast cancer risk (OR 1.18 per SD, 95% CI: 1.07–1.30, P = 0.11 × 10–2), but there was no evidence of association for genetically predicted CPD (OR 1.02, 95% CI: 0.78–1.19, P = 0.85). The sensitivity analyses yielded similar results and showed no strong evidence of pleiotropic effect. Conclusion Our MR study provides supportive evidence for a potential causal association with breast cancer risk for lifetime smoking exposure but not cigarettes per day among smokers.
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- 2021
36. The predictive ability of the 313 variant-based polygenic risk score for contralateral breast cancer risk prediction in women of European ancestry with a heterozygous BRCA1 or BRCA2 pathogenic variant
- Author
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Lakeman, I.M.M., Broek, A.J. van den, Vos, Janet R., Barnes, D.R., Adlard, J., Andrulis, I.L., Arason, A., Arnold, N., Arun, B.K., Balmaña, J., Barrowdale, D., Benitez, J., Borg, A., Caldés, T., Caligo, M.A., Chung, W.K., Claes, K.B.M., Collée, J.M., Couch, F.J., Daly, M.B., Dennis, J., Dhawan, M., Domchek, S.M., Eeles, R., Engel, C., Evans, D.G., Feliubadaló, L., Foretova, L., Friedman, E., Frost, D., Ganz, P.A., Garber, J., Gayther, S.A., Gerdes, A.M., Godwin, A.K., Goldgar, D.E., Hahnen, E., Hake, C.R., Hamann, U., Hogervorst, F.B., Hooning, M.J., Hopper, J.L., Hulick, P.J., Imyanitov, E.N., Isaacs, C., Izatt, L., Jakubowska, A., James, P.A., Janavicius, R., Jensen, U.B., Jiao, Y., John, E.M., Joseph, V., Karlan, B.Y., Kets, C.M., Konstantopoulou, I., Kwong, A., Legrand, C., Leslie, G., Lesueur, F., Loud, J.T., Lubiński, J., Manoukian, S., McGuffog, L., Miller, A., Gomes, D.M., Montagna, M., Mouret-Fourme, E., Nathanson, K.L., Neuhausen, S.L., Nevanlinna, H., Yie, J.N.Y., Olah, E., Olopade, O.I., Park, S.K., Parsons, M.T., Peterlongo, P., Piedmonte, M., Radice, P., Rantala, J., Rennert, G., Risch, H.A., Schmutzler, R.K., Sharma, P., Simard, J., Singer, C.F., Stadler, Z., Stoppa-Lyonnet, D., Sutter, C., Tan, Y.Y., Teixeira, M.R., Teo, S.H., Teulé, A., Thomassen, M., Thull, D.L., Tischkowitz, M., Toland, A.E., Tung, N., Rensburg, E.J. van, Vega, A., Robson, M., Schmidt, M.K., Lakeman, I.M.M., Broek, A.J. van den, Vos, Janet R., Barnes, D.R., Adlard, J., Andrulis, I.L., Arason, A., Arnold, N., Arun, B.K., Balmaña, J., Barrowdale, D., Benitez, J., Borg, A., Caldés, T., Caligo, M.A., Chung, W.K., Claes, K.B.M., Collée, J.M., Couch, F.J., Daly, M.B., Dennis, J., Dhawan, M., Domchek, S.M., Eeles, R., Engel, C., Evans, D.G., Feliubadaló, L., Foretova, L., Friedman, E., Frost, D., Ganz, P.A., Garber, J., Gayther, S.A., Gerdes, A.M., Godwin, A.K., Goldgar, D.E., Hahnen, E., Hake, C.R., Hamann, U., Hogervorst, F.B., Hooning, M.J., Hopper, J.L., Hulick, P.J., Imyanitov, E.N., Isaacs, C., Izatt, L., Jakubowska, A., James, P.A., Janavicius, R., Jensen, U.B., Jiao, Y., John, E.M., Joseph, V., Karlan, B.Y., Kets, C.M., Konstantopoulou, I., Kwong, A., Legrand, C., Leslie, G., Lesueur, F., Loud, J.T., Lubiński, J., Manoukian, S., McGuffog, L., Miller, A., Gomes, D.M., Montagna, M., Mouret-Fourme, E., Nathanson, K.L., Neuhausen, S.L., Nevanlinna, H., Yie, J.N.Y., Olah, E., Olopade, O.I., Park, S.K., Parsons, M.T., Peterlongo, P., Piedmonte, M., Radice, P., Rantala, J., Rennert, G., Risch, H.A., Schmutzler, R.K., Sharma, P., Simard, J., Singer, C.F., Stadler, Z., Stoppa-Lyonnet, D., Sutter, C., Tan, Y.Y., Teixeira, M.R., Teo, S.H., Teulé, A., Thomassen, M., Thull, D.L., Tischkowitz, M., Toland, A.E., Tung, N., Rensburg, E.J. van, Vega, A., Robson, M., and Schmidt, M.K.
- Abstract
Contains fulltext : 244113.pdf (Publisher’s version ) (Open Access), PURPOSE: To evaluate the association between a previously published 313 variant-based breast cancer (BC) polygenic risk score (PRS(313)) and contralateral breast cancer (CBC) risk, in BRCA1 and BRCA2 pathogenic variant heterozygotes. METHODS: We included women of European ancestry with a prevalent first primary invasive BC (BRCA1 = 6,591 with 1,402 prevalent CBC cases; BRCA2 = 4,208 with 647 prevalent CBC cases) from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), a large international retrospective series. Cox regression analysis was performed to assess the association between overall and ER-specific PRS(313) and CBC risk. RESULTS: For BRCA1 heterozygotes the estrogen receptor (ER)-negative PRS(313) showed the largest association with CBC risk, hazard ratio (HR) per SD = 1.12, 95% confidence interval (CI) (1.06-1.18), C-index = 0.53; for BRCA2 heterozygotes, this was the ER-positive PRS(313), HR = 1.15, 95% CI (1.07-1.25), C-index = 0.57. Adjusting for family history, age at diagnosis, treatment, or pathological characteristics for the first BC did not change association effect sizes. For women developing first BC < age 40 years, the cumulative PRS(313) 5th and 95th percentile 10-year CBC risks were 22% and 32% for BRCA1 and 13% and 23% for BRCA2 heterozygotes, respectively. CONCLUSION: The PRS(313) can be used to refine individual CBC risks for BRCA1/2 heterozygotes of European ancestry, however the PRS(313) needs to be considered in the context of a multifactorial risk model to evaluate whether it might influence clinical decision-making.
- Published
- 2021
37. A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers
- Author
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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
- Full Text
- View/download PDF
38. 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
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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
39. Breast cancer risk factors and survival by tumor subtype: Pooled analyses from the breast cancer association consortium.
- Author
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Morra A., Jung A.Y., Behrens S., Keeman R., Ahearn T.U., Anton-Culver H., Arndt V., Augustinsson A., Auvinen P.K., Beane Freeman L.E., Becher H., Beckmann M.W., Blomqvist C., Bojesen S.E., Bolla M.K., Brenner H., Briceno I., Brucker S.Y., Camp N.J., Campa D., Canzian F., Castelao J.E., Chanock S.J., Choi J.-Y., Clarke C.L., Couch F.J., Cox A., Cross S.S., Czene K., Dork T., Dunning A.M., Dwek M., Easton D.F., Eccles D.M., Egan K.M., Evans D.G., Fasching P.A., Flyger H., Gago-Dominguez M., Gapstur S.M., Garcia-Saenz J.A., Gaudet M.M., Giles G.G., Grip M., Guenel P., Haiman C.A., Hakansson N., Hall P., Hamann U., Han S.N., Hart S.N., Hartman M., Heyworth J.S., Hoppe R., Hopper J.L., Hunter D.J., Ito H., Jager A., Jakimovska M., Jakubowska A., Janni W., Kaaks R., Kang D., Kapoor P.M., Kitahara C.M., Koutros S., Kraft P., Kristensen V.N., Lacey J.V., Lambrechts D., Le Marchand L., Li J., Lindblom A., Lubi-Nski J., Lush M., Mannermaa A., Manoochehri M., Margolin S., Mariapun S., Matsuo K., Mavroudis D., Milne R.L., Muranen T.A., Newman W.G., Noh D.-Y., Nordestgaard B.G., Obi N., Olshan A.F., Olsson H., Park-Simon T.-W., Petridis C., Pharoah P.D.P., Plaseska-Karanfilska D., Presneau N., Rashid M.U., Rennert G., Rennert H.S., Rhenius V., Romero A., Saloustros E., Sawyer E.J., Schneeweiss A., Schwentner L., Scott C., Shah M., Shen C.-Y., Shu X.-O., Southey M.C., Stram D.O., Tamimi R.M., Tapper W., Tollenaar R.A.E.M., Tomlinson I., Torres D., Troester M.A., Therese Truong, Vachon C.M., Wang Q., Wang S.S., Williams J.A., Winqvist R., Wolk A., Wu A.H., Yoo K.-Y., Yu J.-C., Zheng W., Ziogas A., Yang X.R., Eliassen A.H., Holmes M.D., Garcia-Closas M., Teo S.H., Schmidt M.K., Chang-Claude J., Morra A., Jung A.Y., Behrens S., Keeman R., Ahearn T.U., Anton-Culver H., Arndt V., Augustinsson A., Auvinen P.K., Beane Freeman L.E., Becher H., Beckmann M.W., Blomqvist C., Bojesen S.E., Bolla M.K., Brenner H., Briceno I., Brucker S.Y., Camp N.J., Campa D., Canzian F., Castelao J.E., Chanock S.J., Choi J.-Y., Clarke C.L., Couch F.J., Cox A., Cross S.S., Czene K., Dork T., Dunning A.M., Dwek M., Easton D.F., Eccles D.M., Egan K.M., Evans D.G., Fasching P.A., Flyger H., Gago-Dominguez M., Gapstur S.M., Garcia-Saenz J.A., Gaudet M.M., Giles G.G., Grip M., Guenel P., Haiman C.A., Hakansson N., Hall P., Hamann U., Han S.N., Hart S.N., Hartman M., Heyworth J.S., Hoppe R., Hopper J.L., Hunter D.J., Ito H., Jager A., Jakimovska M., Jakubowska A., Janni W., Kaaks R., Kang D., Kapoor P.M., Kitahara C.M., Koutros S., Kraft P., Kristensen V.N., Lacey J.V., Lambrechts D., Le Marchand L., Li J., Lindblom A., Lubi-Nski J., Lush M., Mannermaa A., Manoochehri M., Margolin S., Mariapun S., Matsuo K., Mavroudis D., Milne R.L., Muranen T.A., Newman W.G., Noh D.-Y., Nordestgaard B.G., Obi N., Olshan A.F., Olsson H., Park-Simon T.-W., Petridis C., Pharoah P.D.P., Plaseska-Karanfilska D., Presneau N., Rashid M.U., Rennert G., Rennert H.S., Rhenius V., Romero A., Saloustros E., Sawyer E.J., Schneeweiss A., Schwentner L., Scott C., Shah M., Shen C.-Y., Shu X.-O., Southey M.C., Stram D.O., Tamimi R.M., Tapper W., Tollenaar R.A.E.M., Tomlinson I., Torres D., Troester M.A., Therese Truong, Vachon C.M., Wang Q., Wang S.S., Williams J.A., Winqvist R., Wolk A., Wu A.H., Yoo K.-Y., Yu J.-C., Zheng W., Ziogas A., Yang X.R., Eliassen A.H., Holmes M.D., Garcia-Closas M., Teo S.H., Schmidt M.K., and Chang-Claude J.
- Abstract
Background: It is not known whether modifiable lifestyle factors that predict survival after invasive breast cancer differ by subtype. Method(s): We analyzed data for 121,435 women diagnosed with breast cancer from 67 studies in the Breast Cancer Association Consortium with 16,890 deaths (8,554 breast cancer specific) over 10 years. Cox regression was used to estimate associations between risk factors and 10-year all-cause mortality and breast cancer. specific mortality overall, by estrogen receptor (ER) status, and by intrinsic-like subtype. Result(s): There was no evidence of heterogeneous associations between risk factors and mortality by subtype (Padj > 0.30). The strongest associations were between all-cause mortality and BMI >=30 versus 18.5.25 kg/m2 [HR (95% confidence interval (CI), 1.19 (1.06-1.34)]; current versus never smoking [1.37 (1.27-1.47)], high versus low physical activity [0.43 (0.21-0.86)], age >=30 years versus <20 years at first pregnancy [0.79 (0.72-0.86)]; >0.<5 years versus >=10 years since last full-term birth [1.31 (1.11-1.55)]; ever versus never use of oral contraceptives [0.91 (0.87-0.96)]; ever versus never use of menopausal hormone therapy, including current estrogen.progestin therapy [0.61 (0.54.0.69)]. Similar associations with breast cancer mortality were weaker; for example, 1.11 (1.02-1.21) for current versus never smoking. Conclusion(s): We confirm associations between modifiable lifestyle factors and 10-year all-cause mortality. There was no strong evidence that associations differed by ER status or intrinsic-like subtype. Impact: Given the large dataset and lack of evidence that associations between modifiable risk factors and 10-year mortality differed by subtype, these associations could be cautiously used in prognostication models to inform patient-centered care.Copyright © 2021 American Association for Cancer Research.
- Published
- 2021
40. Mendelian randomisation study of smoking exposure in relation to breast cancer risk.
- Author
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Park H.A., Neumeyer S., Michailidou K., Bolla M.K., Wang Q., Dennis J., Ahearn T.U., Andrulis I.L., Anton-Culver H., Antonenkova N.N., Arndt V., Aronson K.J., Augustinsson A., Baten A., Beane Freeman L.E., Becher H., Beckmann M.W., Behrens S., Benitez J., Bermisheva M., Bogdanova N.V., Bojesen S.E., Brauch H., Brenner H., Brucker S.Y., Burwinkel B., Campa D., Canzian F., Castelao J.E., Chanock S.J., Clarke C.L., Borresen-Dale A.-L., Grenaker Alnaes G.I., Sahlberg K.K., Ottestad L., Karesen R., Schlichting E., Holmen M.M., Sauer T., Haakensen V., Engebraten O., Naume B., Fossa A., Kiserud C.E., Reinertsen K.V., Helland A., Riis M., Geisler J., Conroy D.M., Couch F.J., Cox A., Cross S.S., Czene K., Daly M.B., Devilee P., Dork T., dos-Santos-Silva I., Dwek M., Eccles D.M., Eliassen A.H., Engel C., Eriksson M., Evans D.G., Fasching P.A., Flyger H., Fritschi L., Garcia-Closas M., Garcia-Saenz J.A., Gaudet M.M., Giles G.G., Glendon G., Goldberg M.S., Goldgar D.E., Gonzalez-Neira A., Grip M., Guenel P., Hahnen E., Haiman C.A., Hakansson N., Hall P., Hamann U., Han S., Harkness E.F., Hart S.N., He W., Heemskerk-Gerritsen B.A.M., Hopper J.L., Hunter D.J., Clarke C., Baxter R., Yip D., Carpenter J., Davis A., Pathmanathan N., Graham D., Sachchithananthan M., Amor D., Andrews L., Antill Y., Balleine R., Beesley J., Bennett I., Bogwitz M., Botes L., Brennan M., Brown M., Buckley M., Burke J., Butow P., Caldon L., Campbell I., Chauhan D., Chauhan M., Chenevix-Trench G., Christian A., Cohen P., Colley A., Crook A., Cui J., Cummings M., Dawson S.-J., DeFazio A., Delatycki M., Dickson R., Dixon J., Edkins T., Edwards S., Farshid G., Fellows A., Fenton G., Field M., Flanagan J., Fong P., Forrest L., Fox S., French J., Friedlander M., Gaff C., Gattas M., George P., Greening S., Harris M., Hart S., Hayward N., Hopper J., Hoskins C., Hunt C., James P., Jenkins M., Kidd A., Kirk J., Koehler J., Kollias J., Lakhani S., Lawrence M., Lindeman G., Lipton L., Lobb L., Mann G., Marsh D., McLachlan S.A., Meiser B., Milne R., Nightingale S., O'Connell S., O'Sullivan S., Ortega D.G., Pachter N., Patterson B., Pearn A., Phillips K., Pieper E., Rickard E., Robinson B., Saleh M., Salisbury E., Saunders C., Saunus J., Scott R., Sexton A., Shelling A., Simpson P., Southey M., Spurdle A., Taylor J., Taylor R., Thorne H., Trainer A., Tucker K., Visvader J., Walker L., Williams R., Winship I., Young M.A., Jager A., Jakubowska A., John E.M., Jung A., Kaaks R., Kapoor P.M., Keeman R., Khusnutdinova E., Kitahara C.M., Koppert L.B., Koutros S., Kristensen V.N., Kurian A.W., Lacey J., Lambrechts D., Le Marchand L., Lo W.-Y., Lubinski J., Mannermaa A., Manoochehri M., Margolin S., Martinez M.E., Mavroudis D., Meindl A., Menon U., Milne R.L., Muranen T.A., Nevanlinna H., Newman W.G., Nordestgaard B.G., Offit K., Olshan A.F., Olsson H., Park-Simon T.-W., Peterlongo P., Peto J., Plaseska-Karanfilska D., Presneau N., Radice P., Rennert G., Rennert H.S., Romero A., Saloustros E., Sawyer E.J., Schmidt M.K., Schmutzler R.K., Schoemaker M.J., Schwentner L., Scott C., Shah M., Shu X.-O., Simard J., Smeets A., Southey M.C., Spinelli J.J., Stevens V., Swerdlow A.J., Tamimi R.M., Tapper W.J., Taylor J.A., Terry M.B., Tomlinson I., Troester M.A., Truong T., Vachon C.M., van Veen E.M., Vijai J., Wang S., Wendt C., Winqvist R., Wolk A., Ziogas A., Dunning A.M., Pharoah P.D.P., Easton D.F., Zheng W., Kraft P., Chang-Claude J., Park H.A., Neumeyer S., Michailidou K., Bolla M.K., Wang Q., Dennis J., Ahearn T.U., Andrulis I.L., Anton-Culver H., Antonenkova N.N., Arndt V., Aronson K.J., Augustinsson A., Baten A., Beane Freeman L.E., Becher H., Beckmann M.W., Behrens S., Benitez J., Bermisheva M., Bogdanova N.V., Bojesen S.E., Brauch H., Brenner H., Brucker S.Y., Burwinkel B., Campa D., Canzian F., Castelao J.E., Chanock S.J., Clarke C.L., Borresen-Dale A.-L., Grenaker Alnaes G.I., Sahlberg K.K., Ottestad L., Karesen R., Schlichting E., Holmen M.M., Sauer T., Haakensen V., Engebraten O., Naume B., Fossa A., Kiserud C.E., Reinertsen K.V., Helland A., Riis M., Geisler J., Conroy D.M., Couch F.J., Cox A., Cross S.S., Czene K., Daly M.B., Devilee P., Dork T., dos-Santos-Silva I., Dwek M., Eccles D.M., Eliassen A.H., Engel C., Eriksson M., Evans D.G., Fasching P.A., Flyger H., Fritschi L., Garcia-Closas M., Garcia-Saenz J.A., Gaudet M.M., Giles G.G., Glendon G., Goldberg M.S., Goldgar D.E., Gonzalez-Neira A., Grip M., Guenel P., Hahnen E., Haiman C.A., Hakansson N., Hall P., Hamann U., Han S., Harkness E.F., Hart S.N., He W., Heemskerk-Gerritsen B.A.M., Hopper J.L., Hunter D.J., Clarke C., Baxter R., Yip D., Carpenter J., Davis A., Pathmanathan N., Graham D., Sachchithananthan M., Amor D., Andrews L., Antill Y., Balleine R., Beesley J., Bennett I., Bogwitz M., Botes L., Brennan M., Brown M., Buckley M., Burke J., Butow P., Caldon L., Campbell I., Chauhan D., Chauhan M., Chenevix-Trench G., Christian A., Cohen P., Colley A., Crook A., Cui J., Cummings M., Dawson S.-J., DeFazio A., Delatycki M., Dickson R., Dixon J., Edkins T., Edwards S., Farshid G., Fellows A., Fenton G., Field M., Flanagan J., Fong P., Forrest L., Fox S., French J., Friedlander M., Gaff C., Gattas M., George P., Greening S., Harris M., Hart S., Hayward N., Hopper J., Hoskins C., Hunt C., James P., Jenkins M., Kidd A., Kirk J., Koehler J., Kollias J., Lakhani S., Lawrence M., Lindeman G., Lipton L., Lobb L., Mann G., Marsh D., McLachlan S.A., Meiser B., Milne R., Nightingale S., O'Connell S., O'Sullivan S., Ortega D.G., Pachter N., Patterson B., Pearn A., Phillips K., Pieper E., Rickard E., Robinson B., Saleh M., Salisbury E., Saunders C., Saunus J., Scott R., Sexton A., Shelling A., Simpson P., Southey M., Spurdle A., Taylor J., Taylor R., Thorne H., Trainer A., Tucker K., Visvader J., Walker L., Williams R., Winship I., Young M.A., Jager A., Jakubowska A., John E.M., Jung A., Kaaks R., Kapoor P.M., Keeman R., Khusnutdinova E., Kitahara C.M., Koppert L.B., Koutros S., Kristensen V.N., Kurian A.W., Lacey J., Lambrechts D., Le Marchand L., Lo W.-Y., Lubinski J., Mannermaa A., Manoochehri M., Margolin S., Martinez M.E., Mavroudis D., Meindl A., Menon U., Milne R.L., Muranen T.A., Nevanlinna H., Newman W.G., Nordestgaard B.G., Offit K., Olshan A.F., Olsson H., Park-Simon T.-W., Peterlongo P., Peto J., Plaseska-Karanfilska D., Presneau N., Radice P., Rennert G., Rennert H.S., Romero A., Saloustros E., Sawyer E.J., Schmidt M.K., Schmutzler R.K., Schoemaker M.J., Schwentner L., Scott C., Shah M., Shu X.-O., Simard J., Smeets A., Southey M.C., Spinelli J.J., Stevens V., Swerdlow A.J., Tamimi R.M., Tapper W.J., Taylor J.A., Terry M.B., Tomlinson I., Troester M.A., Truong T., Vachon C.M., van Veen E.M., Vijai J., Wang S., Wendt C., Winqvist R., Wolk A., Ziogas A., Dunning A.M., Pharoah P.D.P., Easton D.F., Zheng W., Kraft P., and Chang-Claude J.
- Abstract
Background: Despite a modest association between tobacco smoking and breast cancer risk reported by recent epidemiological studies, it is still equivocal whether smoking is causally related to breast cancer risk. Method(s): We applied Mendelian randomisation (MR) to evaluate a potential causal effect of cigarette smoking on breast cancer risk. Both individual-level data as well as summary statistics for 164 single-nucleotide polymorphisms (SNPs) reported in genome-wide association studies of lifetime smoking index (LSI) or cigarette per day (CPD) were used to obtain MR effect estimates. Data from 108,420 invasive breast cancer cases and 87,681 controls were used for the LSI analysis and for the CPD analysis conducted among ever-smokers from 26,147 cancer cases and 26,072 controls. Sensitivity analyses were conducted to address pleiotropy. Result(s): Genetically predicted LSI was associated with increased breast cancer risk (OR 1.18 per SD, 95% CI: 1.07-1.30, P = 0.11 x 10-2), but there was no evidence of association for genetically predicted CPD (OR 1.02, 95% CI: 0.78-1.19, P = 0.85). The sensitivity analyses yielded similar results and showed no strong evidence of pleiotropic effect. Conclusion(s): Our MR study provides supportive evidence for a potential causal association with breast cancer risk for lifetime smoking exposure but not cigarettes per day among smokers.Copyright © 2021, The Author(s).
- Published
- 2021
41. Genetic insights into biological mechanisms governing human ovarian ageing.
- Author
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Ruth K.S., Day F.R., Hussain J., Martinez-Marchal A., Aiken C.E., Azad A., Thompson D.J., Knoblochova L., Abe H., Tarry-Adkins J.L., Gonzalez J.M., Fontanillas P., Claringbould A., Bakker O.B., Sulem P., Walters R.G., Terao C., Turon S., Horikoshi M., Lin K., Onland-Moret N.C., Sankar A., Hertz E.P.T., Timshel P.N., Shukla V., Borup R., Olsen K.W., Aguilera P., Ferrer-Roda M., Huang Y., Stankovic S., Timmers P.R.H.J., Ahearn T.U., Alizadeh B.Z., Naderi E., Andrulis I.L., Arnold A.M., Aronson K.J., Augustinsson A., Bandinelli S., Barbieri C.M., Beaumont R.N., Becher H., Beckmann M.W., Benonisdottir S., Bergmann S., Bochud M., Boerwinkle E., Bojesen S.E., Bolla M.K., Boomsma D.I., Bowker N., Brody J.A., Broer L., Buring J.E., Campbell A., Campbell H., Castelao J.E., Catamo E., Chanock S.J., Chenevix-Trench G., Ciullo M., Corre T., Couch F.J., Cox A., Crisponi L., Cross S.S., Cucca F., Czene K., Smith G.D., de Geus E.J.C.N., de Mutsert R., De Vivo I., Demerath E.W., Dennis J., Dunning A.M., Dwek M., Eriksson M., Esko T., Fasching P.A., Faul J.D., Ferrucci L., Franceschini N., Frayling T.M., Gago-Dominguez M., Mezzavilla M., Garcia-Closas M., Gieger C., Giles G.G., Grallert H., Gudbjartsson D.F., Gudnason V., Guenel P., Haiman C.A., Hakansson N., Hall P., Hayward C., He C., He W., Heiss G., Hoffding M.K., Hopper J.L., Hottenga J.J., Hu F., Hunter D., Ikram M.A., Jackson R.D., Joaquim M.D.R., John E.M., Joshi P.K., Karasik D., Kardia S.L.R., Kartsonaki C., Karlsson R., Kitahara C.M., Kolcic I., Kooperberg C., Kraft P., Kurian A.W., Kutalik Z., La Bianca M., LaChance G., Langenberg C., Launer L.J., Laven J.S.E., Lawlor D.A., Le Marchand L., Li J., Lindblom A., Lindstrom S., Lindstrom T., Linet M., Liu Y.M., Liu S., Luan J., Magi R., Magnusson P.K.E., Mangino M., Mannermaa A., Marco B., Marten J., Martin N.G., Mbarek H., McKnight B., Medland S.E., Meisinger C., Meitinger T., Menni C., Metspalu A., Milani L., Milne R.L., Montgomery G.W., Mook-Kanamori D.O., Mulas A., Mulligan A.M., Nalls M.A., Newman A., Noordam R., Nutile T., Nyholt D.R., Olshan A.F., Olsson H., Painter J.N., Patel A.V., Pedersen N.L., Perjakova N., Peters A., Peters U., Pharoah P.D.P., Polasek O., Porcu E., Psaty B.M., Rahman I., Rennert G., Rennert H.S., Ridker P.M., Ring S.M., Robino A., Rose L.M., Rosendaal F.R., Rossouw J., Rudan I., Rueedi R., Ruggiero D., Sala C.F., Saloustros E., Sandler D.P., Sanna S., Sawyer E.J., Sarnowski C., Schlessinger D., Schmidt M.K., Schoemaker M.J., Schraut K.E., Scott C., Shekari S., Shrikhande A., Smith A.V., Smith B.H., Smith J.A., Sorice R., Southey M.C., Spector T.D., Spinelli J.J., Stampfer M., Stockl D., van Meurs J.B.J., Strauch K., Styrkarsdottir U., Swerdlow A.J., Tanaka T., Teras L.R., Teumer A., Thorsteinsdottir U., Timpson N.J., Toniolo D., Traglia M., Troester M.A., Truong T., Tyrrell J., Uitterlinden A.G., Ulivi S., Vachon C.M., Vitart V., Volker U., Vollenweider P., Volzke H., Wang Q., Wareham N.J., Weinberg C.R., Weir D.R., Wilcox A.N., van Dijk K.W., Willemsen G., Wilson J.F., Wolffenbuttel B.H.R., Wolk A., Wood A.R., Zhao W., Zygmunt M., Chen Z., Li L., Franke L., Burgess S., Deelen P., Pers T.H., Grondahl M.L., Andersen C.Y., Pujol A., Lopez-Contreras A.J., Daniel J.A., Stefansson K., Chang-Claude J., van der Schouw Y.T., Lunetta K.L., Chasman D.I., Easton D.F., Visser J.A., Ozanne S.E., Namekawa S.H., Solc P., Murabito J.M., Ong K.K., Hoffmann E.R., Murray A., Roig I., Perry J.R.B., Ruth K.S., Day F.R., Hussain J., Martinez-Marchal A., Aiken C.E., Azad A., Thompson D.J., Knoblochova L., Abe H., Tarry-Adkins J.L., Gonzalez J.M., Fontanillas P., Claringbould A., Bakker O.B., Sulem P., Walters R.G., Terao C., Turon S., Horikoshi M., Lin K., Onland-Moret N.C., Sankar A., Hertz E.P.T., Timshel P.N., Shukla V., Borup R., Olsen K.W., Aguilera P., Ferrer-Roda M., Huang Y., Stankovic S., Timmers P.R.H.J., Ahearn T.U., Alizadeh B.Z., Naderi E., Andrulis I.L., Arnold A.M., Aronson K.J., Augustinsson A., Bandinelli S., Barbieri C.M., Beaumont R.N., Becher H., Beckmann M.W., Benonisdottir S., Bergmann S., Bochud M., Boerwinkle E., Bojesen S.E., Bolla M.K., Boomsma D.I., Bowker N., Brody J.A., Broer L., Buring J.E., Campbell A., Campbell H., Castelao J.E., Catamo E., Chanock S.J., Chenevix-Trench G., Ciullo M., Corre T., Couch F.J., Cox A., Crisponi L., Cross S.S., Cucca F., Czene K., Smith G.D., de Geus E.J.C.N., de Mutsert R., De Vivo I., Demerath E.W., Dennis J., Dunning A.M., Dwek M., Eriksson M., Esko T., Fasching P.A., Faul J.D., Ferrucci L., Franceschini N., Frayling T.M., Gago-Dominguez M., Mezzavilla M., Garcia-Closas M., Gieger C., Giles G.G., Grallert H., Gudbjartsson D.F., Gudnason V., Guenel P., Haiman C.A., Hakansson N., Hall P., Hayward C., He C., He W., Heiss G., Hoffding M.K., Hopper J.L., Hottenga J.J., Hu F., Hunter D., Ikram M.A., Jackson R.D., Joaquim M.D.R., John E.M., Joshi P.K., Karasik D., Kardia S.L.R., Kartsonaki C., Karlsson R., Kitahara C.M., Kolcic I., Kooperberg C., Kraft P., Kurian A.W., Kutalik Z., La Bianca M., LaChance G., Langenberg C., Launer L.J., Laven J.S.E., Lawlor D.A., Le Marchand L., Li J., Lindblom A., Lindstrom S., Lindstrom T., Linet M., Liu Y.M., Liu S., Luan J., Magi R., Magnusson P.K.E., Mangino M., Mannermaa A., Marco B., Marten J., Martin N.G., Mbarek H., McKnight B., Medland S.E., Meisinger C., Meitinger T., Menni C., Metspalu A., Milani L., Milne R.L., Montgomery G.W., Mook-Kanamori D.O., Mulas A., Mulligan A.M., Nalls M.A., Newman A., Noordam R., Nutile T., Nyholt D.R., Olshan A.F., Olsson H., Painter J.N., Patel A.V., Pedersen N.L., Perjakova N., Peters A., Peters U., Pharoah P.D.P., Polasek O., Porcu E., Psaty B.M., Rahman I., Rennert G., Rennert H.S., Ridker P.M., Ring S.M., Robino A., Rose L.M., Rosendaal F.R., Rossouw J., Rudan I., Rueedi R., Ruggiero D., Sala C.F., Saloustros E., Sandler D.P., Sanna S., Sawyer E.J., Sarnowski C., Schlessinger D., Schmidt M.K., Schoemaker M.J., Schraut K.E., Scott C., Shekari S., Shrikhande A., Smith A.V., Smith B.H., Smith J.A., Sorice R., Southey M.C., Spector T.D., Spinelli J.J., Stampfer M., Stockl D., van Meurs J.B.J., Strauch K., Styrkarsdottir U., Swerdlow A.J., Tanaka T., Teras L.R., Teumer A., Thorsteinsdottir U., Timpson N.J., Toniolo D., Traglia M., Troester M.A., Truong T., Tyrrell J., Uitterlinden A.G., Ulivi S., Vachon C.M., Vitart V., Volker U., Vollenweider P., Volzke H., Wang Q., Wareham N.J., Weinberg C.R., Weir D.R., Wilcox A.N., van Dijk K.W., Willemsen G., Wilson J.F., Wolffenbuttel B.H.R., Wolk A., Wood A.R., Zhao W., Zygmunt M., Chen Z., Li L., Franke L., Burgess S., Deelen P., Pers T.H., Grondahl M.L., Andersen C.Y., Pujol A., Lopez-Contreras A.J., Daniel J.A., Stefansson K., Chang-Claude J., van der Schouw Y.T., Lunetta K.L., Chasman D.I., Easton D.F., Visser J.A., Ozanne S.E., Namekawa S.H., Solc P., Murabito J.M., Ong K.K., Hoffmann E.R., Murray A., Roig I., and Perry J.R.B.
- Abstract
Reproductive longevity is essential for fertility and influences healthy ageing in women1,2, but insights into its underlying biological mechanisms and treatments to preserve it are limited. Here we identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in about 200,000 women of European ancestry. These common alleles were associated with clinical extremes of ANM; women in the top 1% of genetic susceptibility have an equivalent risk of premature ovarian insufficiency to those carrying monogenic FMR1 premutations3. The identified loci implicate a broad range of DNA damage response (DDR) processes and include loss-of-function variants in key DDR-associated genes. Integration with experimental models demonstrates that these DDR processes act across the life-course to shape the ovarian reserve and its rate of depletion. Furthermore, we demonstrate that experimental manipulation of DDR pathways highlighted by human genetics increases fertility and extends reproductive life in mice. Causal inference analyses using the identified genetic variants indicate that extending reproductive life in women improves bone health and reduces risk of type 2 diabetes, but increases the risk of hormone-sensitive cancers. These findings provide insight into the mechanisms that govern ovarian ageing, when they act, and how they might be targeted by therapeutic approaches to extend fertility and prevent disease.Copyright © 2021, The Author(s), under exclusive licence to Springer Nature Limited.
- Published
- 2021
42. 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
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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
43. Functional annotation of the 2q35 breast cancer risk locus implicates a structural variant in influencing activity of a long-range enhancer element.
- Author
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Baxter J.S., Johnson N., Tomczyk K., Gillespie A., Maguire S., Brough R., Fachal L., Michailidou K., Bolla M.K., Wang Q., Dennis J., Ahearn T.U., Andrulis I.L., Anton-Culver H., Antonenkova N.N., Arndt V., Aronson K.J., Augustinsson A., Becher H., Beckmann M.W., Behrens S., Benitez J., Bermisheva M., Bogdanova N.V., Bojesen S.E., Brenner H., Brucker S.Y., Cai Q., Campa D., Canzian F., Castelao J.E., Chan T.L., Chang-Claude J., Chanock S.J., Chenevix-Trench G., Choi J.-Y., Clarke C.L., Colonna S., Conroy D.M., Couch F.J., Cox A., Cross S.S., Czene K., Daly M.B., Devilee P., Dork T., Dossus L., Dwek M., Eccles D.M., Ekici A.B., Eliassen A.H., Engel C., Fasching P.A., Figueroa J., Flyger H., Gago-Dominguez M., Gao C., Garcia-Closas M., Garcia-Saenz J.A., Ghoussaini M., Giles G.G., Goldberg M.S., Gonzalez-Neira A., Guenel P., Gundert M., Haeberle L., Hahnen E., Haiman C.A., Hall P., Hamann U., Hartman M., Hatse S., Hauke J., Hollestelle A., Hoppe R., Hopper J.L., Hou M.-F., Ito H., Iwasaki M., Jager A., Jakubowska A., Janni W., John E.M., Joseph V., Jung A., Kaaks R., Kang D., Keeman R., Khusnutdinova E., Kim S.-W., Kosma V.-M., Kraft P., Kristensen V.N., Kubelka-Sabit K., Kurian A.W., Kwong A., Lacey J.V., Lambrechts D., Larson N.L., Larsson S.C., Le Marchand L., Lejbkowicz F., Li J., Long J., Lophatananon A., Lubinski J., Mannermaa A., Manoochehri M., Manoukian S., Margolin S., Matsuo K., Mavroudis D., Mayes R., Menon U., Milne R.L., Mohd Taib N.A., Muir K., Muranen T.A., Murphy R.A., Nevanlinna H., O'Brien K.M., Offit K., Olson J.E., Olsson H., Park S.K., Park-Simon T.-W., Patel A.V., Peterlongo P., Peto J., Plaseska-Karanfilska D., Presneau N., Pylkas K., Rack B., Rennert G., Romero A., Ruebner M., Rudiger T., Saloustros E., Sandler D.P., Sawyer E.J., Schmidt M.K., Schmutzler R.K., Schneeweiss A., Schoemaker M.J., Shah M., Shen C.-Y., Shu X.-O., Simard J., Southey M.C., Stone J., Surowy H., Swerdlow A.J., Tamimi R.M., Tapper W.J., Taylor J.A., Teo S.H., Teras L.R., Terry M.B., Toland A.E., Tomlinson I., Truong T., Tseng C.-C., Untch M., Vachon C.M., van den Ouweland A.M.W., Wang S.S., Weinberg C.R., Wendt C., Winham S.J., Winqvist R., Wolk A., Wu A.H., Yamaji T., Zheng W., Ziogas A., Pharoah P.D.P., Dunning A.M., Easton D.F., Pettitt S.J., Lord C.J., Haider S., Orr N., Fletcher O., Baxter J.S., Johnson N., Tomczyk K., Gillespie A., Maguire S., Brough R., Fachal L., Michailidou K., Bolla M.K., Wang Q., Dennis J., Ahearn T.U., Andrulis I.L., Anton-Culver H., Antonenkova N.N., Arndt V., Aronson K.J., Augustinsson A., Becher H., Beckmann M.W., Behrens S., Benitez J., Bermisheva M., Bogdanova N.V., Bojesen S.E., Brenner H., Brucker S.Y., Cai Q., Campa D., Canzian F., Castelao J.E., Chan T.L., Chang-Claude J., Chanock S.J., Chenevix-Trench G., Choi J.-Y., Clarke C.L., Colonna S., Conroy D.M., Couch F.J., Cox A., Cross S.S., Czene K., Daly M.B., Devilee P., Dork T., Dossus L., Dwek M., Eccles D.M., Ekici A.B., Eliassen A.H., Engel C., Fasching P.A., Figueroa J., Flyger H., Gago-Dominguez M., Gao C., Garcia-Closas M., Garcia-Saenz J.A., Ghoussaini M., Giles G.G., Goldberg M.S., Gonzalez-Neira A., Guenel P., Gundert M., Haeberle L., Hahnen E., Haiman C.A., Hall P., Hamann U., Hartman M., Hatse S., Hauke J., Hollestelle A., Hoppe R., Hopper J.L., Hou M.-F., Ito H., Iwasaki M., Jager A., Jakubowska A., Janni W., John E.M., Joseph V., Jung A., Kaaks R., Kang D., Keeman R., Khusnutdinova E., Kim S.-W., Kosma V.-M., Kraft P., Kristensen V.N., Kubelka-Sabit K., Kurian A.W., Kwong A., Lacey J.V., Lambrechts D., Larson N.L., Larsson S.C., Le Marchand L., Lejbkowicz F., Li J., Long J., Lophatananon A., Lubinski J., Mannermaa A., Manoochehri M., Manoukian S., Margolin S., Matsuo K., Mavroudis D., Mayes R., Menon U., Milne R.L., Mohd Taib N.A., Muir K., Muranen T.A., Murphy R.A., Nevanlinna H., O'Brien K.M., Offit K., Olson J.E., Olsson H., Park S.K., Park-Simon T.-W., Patel A.V., Peterlongo P., Peto J., Plaseska-Karanfilska D., Presneau N., Pylkas K., Rack B., Rennert G., Romero A., Ruebner M., Rudiger T., Saloustros E., Sandler D.P., Sawyer E.J., Schmidt M.K., Schmutzler R.K., Schneeweiss A., Schoemaker M.J., Shah M., Shen C.-Y., Shu X.-O., Simard J., Southey M.C., Stone J., Surowy H., Swerdlow A.J., Tamimi R.M., Tapper W.J., Taylor J.A., Teo S.H., Teras L.R., Terry M.B., Toland A.E., Tomlinson I., Truong T., Tseng C.-C., Untch M., Vachon C.M., van den Ouweland A.M.W., Wang S.S., Weinberg C.R., Wendt C., Winham S.J., Winqvist R., Wolk A., Wu A.H., Yamaji T., Zheng W., Ziogas A., Pharoah P.D.P., Dunning A.M., Easton D.F., Pettitt S.J., Lord C.J., Haider S., Orr N., and Fletcher O.
- Abstract
A combination of genetic and functional approaches has identified three independent breast cancer risk loci at 2q35. A recent fine-scale mapping analysis to refine these associations resulted in 1 (signal 1), 5 (signal 2), and 42 (signal 3) credible causal variants at these loci. We used publicly available in silico DNase I and ChIP-seq data with in vitro reporter gene and CRISPR assays to annotate signals 2 and 3. We identified putative regulatory elements that enhanced cell-type-specific transcription from the IGFBP5 promoter at both signals (30- to 40-fold increased expression by the putative regulatory element at signal 2, 2- to 3-fold by the putative regulatory element at signal 3). We further identified one of the five credible causal variants at signal 2, a 1.4 kb deletion (esv3594306), as the likely causal variant; the deletion allele of this variant was associated with an average additional increase in IGFBP5 expression of 1.3-fold (MCF-7) and 2.2-fold (T-47D). We propose a model in which the deletion allele of esv3594306 juxtaposes two transcription factor binding regions (annotated by estrogen receptor alpha ChIP-seq peaks) to generate a single extended regulatory element. This regulatory element increases cell-type-specific expression of the tumor suppressor gene IGFBP5 and, thereby, reduces risk of estrogen receptor-positive breast cancer (odds ratio = 0.77, 95% CI 0.74-0.81, p = 3.1 x 10-31).Copyright © 2021 The Authors
- Published
- 2021
44. CYP3A7*1C allele: linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers.
- Author
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Johnson N., Maguire S., Morra A., Kapoor P.M., Tomczyk K., Jones M.E., Schoemaker M.J., Gilham C., Bolla M.K., Wang Q., Dennis J., Ahearn T.U., Andrulis I.L., Anton-Culver H., Antonenkova N.N., Arndt V., Aronson K.J., Augustinsson A., Baynes C., Freeman L.E.B., Beckmann M.W., Benitez J., Bermisheva M., Blomqvist C., Boeckx B., Bogdanova N.V., Bojesen S.E., Brauch H., Brenner H., Burwinkel B., Campa D., Canzian F., Castelao J.E., Chanock S.J., Chenevix-Trench G., Clarke C.L., Borresen-Dale A.-L., Alnaes G.I.G., Sahlberg K.K., Ottestad L., Karesen R., Schlichting E., Holmen M.M., Sauer T., Haakensen V., Engebraten O., Naume B., Fossa A., Kiserud C.E., Reinertsen K.V., Helland A., Riis M., Geisler J., Conroy D.M., Couch F.J., Cox A., Cross S.S., Czene K., Dork T., Eliassen A.H., Engel C., Evans D.G., Fasching P.A., Figueroa J., Floris G., Flyger H., Gago-Dominguez M., Gapstur S.M., Garcia-Closas M., Gaudet M.M., Giles G.G., Goldberg M.S., Gonzalez-Neira A., Bowtell D.D.L., Webb P.M., Guenel P., Hahnen E., Haiman C.A., Hakansson N., Hall P., Hamann U., Harrington P.A., Hart S.N., Hooning M.J., Hopper J.L., Howell A., Hunter D.J., Clarke C., Scott R., Baxter R., Yip D., Carpenter J., Davis A., Pathmanathan N., Graham D., Sachchithananthan M., Amor D., Andrews L., Antill Y., Balleine R., Beesley J., Bennett I., Bogwitz M., Botes L., Brennan M., Brown M., Buckley M., Burke J., Butow P., Caldon L., Campbell I., Chauhan D., Chauhan M., Christian A., Cohen P., Colley A., Crook A., Cui J., Cummings M., Dawson S.-J., DeFazio A., Delatycki M., Dickson R., Dixon J., Edkins T., Edwards S., Farshid G., Fellows A., Fenton G., Field M., Flanagan J., Fong P., Forrest L., Fox S., French J., Friedlander M., Gaff C., Gattas M., George P., Greening S., Harris M., Hart S., Hayward N., Hopper J., Hoskins C., Hunt C., James P., Jenkins M., Kidd A., Kirk J., Koehler J., Kollias J., Lakhani S., Lawrence M., Lindeman G., Lipton L., Lobb L., Mann G., Marsh D., McLachlan S.A., Meiser B., Milne R.L., Nightingale S., O'Connell S., O'Sullivan S., Ortega D.G., Pachter N., Patterson B., Pearn A., Phillips K., Pieper E., Rickard E., Robinson B., Saleh M., Salisbury E., Saunders C., Saunus J., Sexton A., Shelling A., Simpson P., Southey M.C., Spurdle A., Taylor J., Taylor R., Thorne H., Trainer A., Tucker K., Visvader J., Walker L., Williams R., Winship I., Young M.A., Jager A., Jakubowska A., John E.M., Keeman R., Khusnutdinova E., Kitahara C.M., Kosma V.-M., Koutros S., Kraft P., Kristensen V.N., Kurian A.W., Lambrechts D., Le Marchand L., Linet M., Lubinski J., Mannermaa A., Manoukian S., Margolin S., Martens J.W.M., Mavroudis D., Mayes R., Meindl A., Neuhausen S.L., Nevanlinna H., Newman W.G., Nielsen S.F., Nordestgaard B.G., Obi N., Olshan A.F., Olson J.E., Olsson H., Orban E., Park-Simon T.-W., Peterlongo P., Plaseska-Karanfilska D., Pylkas K., Rennert G., Rennert H.S., Ruddy K.J., Saloustros E., Sandler D.P., Sawyer E.J., Schmutzler R.K., Scott C., Shu X.-O., Simard J., Smichkoska S., Sohn C., Spinelli J.J., Stone J., Tamimi R.M., Taylor J.A., Tollenaar R.A.E.M., Tomlinson I., Troester M.A., Truong T., Vachon C.M., van Veen E.M., Wang S.S., Weinberg C.R., Wendt C., Wildiers H., Winqvist R., Wolk A., Zheng W., Ziogas A., Dunning A.M., Pharoah P.D.P., Easton D.F., Howie A.F., Peto J., dos-Santos-Silva I., Swerdlow A.J., Chang-Claude J., Schmidt M.K., Orr N., Fletcher O., Johnson N., Maguire S., Morra A., Kapoor P.M., Tomczyk K., Jones M.E., Schoemaker M.J., Gilham C., Bolla M.K., Wang Q., Dennis J., Ahearn T.U., Andrulis I.L., Anton-Culver H., Antonenkova N.N., Arndt V., Aronson K.J., Augustinsson A., Baynes C., Freeman L.E.B., Beckmann M.W., Benitez J., Bermisheva M., Blomqvist C., Boeckx B., Bogdanova N.V., Bojesen S.E., Brauch H., Brenner H., Burwinkel B., Campa D., Canzian F., Castelao J.E., Chanock S.J., Chenevix-Trench G., Clarke C.L., Borresen-Dale A.-L., Alnaes G.I.G., Sahlberg K.K., Ottestad L., Karesen R., Schlichting E., Holmen M.M., Sauer T., Haakensen V., Engebraten O., Naume B., Fossa A., Kiserud C.E., Reinertsen K.V., Helland A., Riis M., Geisler J., Conroy D.M., Couch F.J., Cox A., Cross S.S., Czene K., Dork T., Eliassen A.H., Engel C., Evans D.G., Fasching P.A., Figueroa J., Floris G., Flyger H., Gago-Dominguez M., Gapstur S.M., Garcia-Closas M., Gaudet M.M., Giles G.G., Goldberg M.S., Gonzalez-Neira A., Bowtell D.D.L., Webb P.M., Guenel P., Hahnen E., Haiman C.A., Hakansson N., Hall P., Hamann U., Harrington P.A., Hart S.N., Hooning M.J., Hopper J.L., Howell A., Hunter D.J., Clarke C., Scott R., Baxter R., Yip D., Carpenter J., Davis A., Pathmanathan N., Graham D., Sachchithananthan M., Amor D., Andrews L., Antill Y., Balleine R., Beesley J., Bennett I., Bogwitz M., Botes L., Brennan M., Brown M., Buckley M., Burke J., Butow P., Caldon L., Campbell I., Chauhan D., Chauhan M., Christian A., Cohen P., Colley A., Crook A., Cui J., Cummings M., Dawson S.-J., DeFazio A., Delatycki M., Dickson R., Dixon J., Edkins T., Edwards S., Farshid G., Fellows A., Fenton G., Field M., Flanagan J., Fong P., Forrest L., Fox S., French J., Friedlander M., Gaff C., Gattas M., George P., Greening S., Harris M., Hart S., Hayward N., Hopper J., Hoskins C., Hunt C., James P., Jenkins M., Kidd A., Kirk J., Koehler J., Kollias J., Lakhani S., Lawrence M., Lindeman G., Lipton L., Lobb L., Mann G., Marsh D., McLachlan S.A., Meiser B., Milne R.L., Nightingale S., O'Connell S., O'Sullivan S., Ortega D.G., Pachter N., Patterson B., Pearn A., Phillips K., Pieper E., Rickard E., Robinson B., Saleh M., Salisbury E., Saunders C., Saunus J., Sexton A., Shelling A., Simpson P., Southey M.C., Spurdle A., Taylor J., Taylor R., Thorne H., Trainer A., Tucker K., Visvader J., Walker L., Williams R., Winship I., Young M.A., Jager A., Jakubowska A., John E.M., Keeman R., Khusnutdinova E., Kitahara C.M., Kosma V.-M., Koutros S., Kraft P., Kristensen V.N., Kurian A.W., Lambrechts D., Le Marchand L., Linet M., Lubinski J., Mannermaa A., Manoukian S., Margolin S., Martens J.W.M., Mavroudis D., Mayes R., Meindl A., Neuhausen S.L., Nevanlinna H., Newman W.G., Nielsen S.F., Nordestgaard B.G., Obi N., Olshan A.F., Olson J.E., Olsson H., Orban E., Park-Simon T.-W., Peterlongo P., Plaseska-Karanfilska D., Pylkas K., Rennert G., Rennert H.S., Ruddy K.J., Saloustros E., Sandler D.P., Sawyer E.J., Schmutzler R.K., Scott C., Shu X.-O., Simard J., Smichkoska S., Sohn C., Spinelli J.J., Stone J., Tamimi R.M., Taylor J.A., Tollenaar R.A.E.M., Tomlinson I., Troester M.A., Truong T., Vachon C.M., van Veen E.M., Wang S.S., Weinberg C.R., Wendt C., Wildiers H., Winqvist R., Wolk A., Zheng W., Ziogas A., Dunning A.M., Pharoah P.D.P., Easton D.F., Howie A.F., Peto J., dos-Santos-Silva I., Swerdlow A.J., Chang-Claude J., Schmidt M.K., Orr N., and Fletcher O.
- Abstract
Background: Epidemiological studies provide strong evidence for a role of endogenous sex hormones in the aetiology of breast cancer. The aim of this analysis was to identify genetic variants that are associated with urinary sex-hormone levels and breast cancer risk. Method(s): We carried out a genome-wide association study of urinary oestrone-3-glucuronide and pregnanediol-3-glucuronide levels in 560 premenopausal women, with additional analysis of progesterone levels in 298 premenopausal women. To test for the association with breast cancer risk, we carried out follow-up genotyping in 90,916 cases and 89,893 controls from the Breast Cancer Association Consortium. All women were of European ancestry. Result(s): For pregnanediol-3-glucuronide, there were no genome-wide significant associations; for oestrone-3-glucuronide, we identified a single peak mapping to the CYP3A locus, annotated by rs45446698. The minor rs45446698-C allele was associated with lower oestrone-3-glucuronide (-49.2%, 95% CI -56.1% to -41.1%, P = 3.1 x 10-18); in follow-up analyses, rs45446698-C was also associated with lower progesterone (-26.7%, 95% CI -39.4% to -11.6%, P = 0.001) and reduced risk of oestrogen and progesterone receptor-positive breast cancer (OR = 0.86, 95% CI 0.82-0.91, P = 6.9 x 10-8). Conclusion(s): The CYP3A7*1C allele is associated with reduced risk of hormone receptor-positive breast cancer possibly mediated via an effect on the metabolism of endogenous sex hormones in premenopausal women.Copyright © 2021, The Author(s).
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- 2021
45. Combined Associations of a Polygenic Risk Score and Classical Risk Factors with Breast Cancer Risk.
- Author
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Kapoor P.M., Mavaddat N., Choudhury P.P., Wilcox A.N., Lindstrom S., Behrens S., Michailidou K., Dennis J., Bolla M.K., Wang Q., Jung A., Abu-Ful Z., Ahearn T., Andrulis I.L., Anton-Culver H., Arndt V., Aronson K.J., Auer P.L., Freeman L.E.B., Becher H., Beckmann M.W., Beeghly-Fadiel A., Benitez J., Bernstein L., Bojesen S.E., Brauch H., Brenner H., Bruning T., Cai Q., Campa D., Canzian F., Carracedo A., Carter B.D., Castelao J.E., Chanock S.J., Chatterjee N., Chenevix-Trench G., Clarke C.L., Couch F.J., Cox A., Cross S.S., Czene K., Dai J.Y., Earp H.S., Ekici A.B., Eliassen A.H., Eriksson M., Evans D.G., Fasching P.A., Figueroa J., Fritschi L., Gabrielson M., Gago-Dominguez M., Gao C., Gapstur S.M., Gaudet M.M., Giles G.G., Gonzalez-Neira A., Guenel P., Haeberle L., Haiman C.A., Hakansson N., Hall P., Hamann U., Hatse S., Heyworth J., Holleczek B., Hoover R.N., Hopper J.L., Howell A., Hunter D.J., John E.M., Jones M.E., Kaaks R., Keeman R., Kitahara C.M., Ko Y.-D., Koutros S., Kurian A.W., Lambrechts D., Le Marchand L., Lee E., Lejbkowicz F., Linet M., Lissowska J., Llaneza A., Macinnis R.J., Martinez M.E., Maurer T., Mclean C., Neuhausen S.L., Newman W.G., Norman A., O'brien K.M., Olshan A.F., Olson J.E., Olsson H., Orr N., Perou C.M., Pita G., Polley E.C., Prentice R.L., Rennert G., Rennert H.S., Ruddy K.J., Sandler D.P., Saunders C., Schoemaker M.J., Schottker B., Schumacher F., Scott C., Scott R.J., Shu X.-O., Smeets A., Southey M.C., Spinelli J.J., Stone J., Swerdlow A.J., Tamimi R.M., Taylor J.A., Troester M.A., Vachon C.M., Van Veen E.M., Wang X., Weinberg C.R., Weltens C., Willett W., Winham S.J., Wolk A., Yang X.R., Zheng W., Ziogas A., Dunning A.M., Pharoah P.D.P., Schmidt M.K., Kraft P., Easton D.F., Milne R.L., Garcia-Closas M., Chang-Claude J., Kapoor P.M., Mavaddat N., Choudhury P.P., Wilcox A.N., Lindstrom S., Behrens S., Michailidou K., Dennis J., Bolla M.K., Wang Q., Jung A., Abu-Ful Z., Ahearn T., Andrulis I.L., Anton-Culver H., Arndt V., Aronson K.J., Auer P.L., Freeman L.E.B., Becher H., Beckmann M.W., Beeghly-Fadiel A., Benitez J., Bernstein L., Bojesen S.E., Brauch H., Brenner H., Bruning T., Cai Q., Campa D., Canzian F., Carracedo A., Carter B.D., Castelao J.E., Chanock S.J., Chatterjee N., Chenevix-Trench G., Clarke C.L., Couch F.J., Cox A., Cross S.S., Czene K., Dai J.Y., Earp H.S., Ekici A.B., Eliassen A.H., Eriksson M., Evans D.G., Fasching P.A., Figueroa J., Fritschi L., Gabrielson M., Gago-Dominguez M., Gao C., Gapstur S.M., Gaudet M.M., Giles G.G., Gonzalez-Neira A., Guenel P., Haeberle L., Haiman C.A., Hakansson N., Hall P., Hamann U., Hatse S., Heyworth J., Holleczek B., Hoover R.N., Hopper J.L., Howell A., Hunter D.J., John E.M., Jones M.E., Kaaks R., Keeman R., Kitahara C.M., Ko Y.-D., Koutros S., Kurian A.W., Lambrechts D., Le Marchand L., Lee E., Lejbkowicz F., Linet M., Lissowska J., Llaneza A., Macinnis R.J., Martinez M.E., Maurer T., Mclean C., Neuhausen S.L., Newman W.G., Norman A., O'brien K.M., Olshan A.F., Olson J.E., Olsson H., Orr N., Perou C.M., Pita G., Polley E.C., Prentice R.L., Rennert G., Rennert H.S., Ruddy K.J., Sandler D.P., Saunders C., Schoemaker M.J., Schottker B., Schumacher F., Scott C., Scott R.J., Shu X.-O., Smeets A., Southey M.C., Spinelli J.J., Stone J., Swerdlow A.J., Tamimi R.M., Taylor J.A., Troester M.A., Vachon C.M., Van Veen E.M., Wang X., Weinberg C.R., Weltens C., Willett W., Winham S.J., Wolk A., Yang X.R., Zheng W., Ziogas A., Dunning A.M., Pharoah P.D.P., Schmidt M.K., Kraft P., Easton D.F., Milne R.L., Garcia-Closas M., and Chang-Claude J.
- Abstract
We evaluated the joint associations between a new 313-variant PRS (PRS313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72 284 cases and 80 354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression and a newly developed case-only method for breast cancer risk overall and by estrogen receptor status. After accounting for multiple testing, we did not find evidence that per-standard deviation PRS313 odds ratio differed across strata defined by individual risk factors. Goodness-of-fit tests did not reject the assumption of a multiplicative model between PRS313 and each risk factor. Variation in projected absolute lifetime risk of breast cancer associated with classical risk factors was greater for women with higher genetic risk (PRS313 and family history) and, on average, 17.5% higher in the highest vs lowest deciles of genetic risk. These findings have implications for risk prevention for women at increased risk of breast cancer. Copyright © 2020 The Author(s).
- Published
- 2021
46. Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants.
- Author
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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
47. A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers.
- Author
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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).
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- 2021
48. Association of body mass index with colorectal cancer risk by genome-wide variants.
- Author
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Giles G.G., Lin Y., Bien S.A., Figueiredo J.C., Harrison T.A., Guinter M.A., Berndt S.I., Brenner H., Chan A.T., Chang-Claude J., Gallinger S.J., Gapstur S.M., Campbell P.T., Giovannucci E., Gruber S.B., Gunter M., Ogino S., Potter J.D., Rennert G., Rennert H.S., Robinson J., Sakoda L.C., Slattery M.L., Song Y., White E., Woods M.O., Casey G., Hsu L., Peters U., Hoffmeister M., Jacobs E.J., Jenkins M.A., Le Marchand L., Li L., McLaughlin J.R., Murphy N., Milne R.L., Newcomb P.A., Newton C., Giles G.G., Lin Y., Bien S.A., Figueiredo J.C., Harrison T.A., Guinter M.A., Berndt S.I., Brenner H., Chan A.T., Chang-Claude J., Gallinger S.J., Gapstur S.M., Campbell P.T., Giovannucci E., Gruber S.B., Gunter M., Ogino S., Potter J.D., Rennert G., Rennert H.S., Robinson J., Sakoda L.C., Slattery M.L., Song Y., White E., Woods M.O., Casey G., Hsu L., Peters U., Hoffmeister M., Jacobs E.J., Jenkins M.A., Le Marchand L., Li L., McLaughlin J.R., Murphy N., Milne R.L., Newcomb P.A., and Newton C.
- Abstract
Background: Body mass index (BMI) is a complex phenotype that may interact with genetic variants to influence colorectal cancer risk. Method(s): We tested multiplicative statistical interactions between BMI (per 5 kg/m2) and approximately 2.7 million single nucleotide polymorphisms with colorectal cancer risk among 14 059 colorectal cancer case (53.2% women) and 14 416 control (53.8% women) participants. All analyses were stratified by sex a priori. Statistical methods included 2-step (ie, Cocktail method) and single-step (ie, case-control logistic regression and a joint 2-degree of freedomtest) procedures. All statistical tests were two-sided. Result(s): Each 5 kg/m2 increase in BMI was associated with higher risks of colorectal cancer, less so for women (odds ratio [OR] = 1.14, 95% confidence intervals [CI] = 1.11 to 1.18; P = 9.75 x 10-17) than for men (OR = 1.26, 95% CI = 1.20 to 1.32; P = 2.13 x 10-24). The 2-step Cocktail method identified an interaction for women, but not men, between BMI and a SMAD7 intronic variant at 18q21.1 (rs4939827; Pobserved = .0009; Pthreshold = .005). A joint 2-degree of freedom test was consistent with this finding for women (joint P = 2.43 x 10-10). Each 5 kg/m2 increase in BMI was more strongly associated with colorectal cancer risk for women with the rs4939827-CC genotype (OR = 1.24, 95% CI = 1.16 to 1.32; P = 2.60 x 10-10) than for women with the CT (OR = 1.14, 95% CI = 1.09 to 1.19; P = 1.04 x 10-8) or TT (OR = 1.07, 95% CI = 1.01 to 1.14; P = .02) genotypes. Conclusion(s): These results provide novel insights on a potential mechanism through which a SMAD7 variant, previously identified as a susceptibility locus for colorectal cancer, and BMI may influence colorectal cancer risk for women.Copyright © The Author(s) 2020.
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- 2021
49. Genetically predicted circulating concentrations of micronutrients and risk of colorectal cancer among individuals of European descent: a Mendelian randomization study.
- Author
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Hampe J., Zuber V., Cross A.J., Perez-Cornago A., Hunter D.J., van Duijnhoven F.J.B., Albanes D., Arndt V., Berndt S.I., Bezieau S., Bishop D.T., Boehm J., Brenner H., Burnett-Hartman A., Campbell P.T., Casey G., Castellvi-Bel S., Chan A.T., Chang-Claude J., de la Chapelle A., Figueiredo J.C., Gallinger S.J., Giles G.G., Goodman P.J., Gsur A., Markozannes G., Hampel H., Hoffmeister M., Jenkins M.A., Keku T.O., Kweon S.-S., Larsson S.C., Le Marchand L., Li C.I., Li L., Lindblom A., Martin V., Milne R.L., Moreno V., Nan H., Nassir R., Newcomb P.A., Offit K., Pharoah P.D.P., Platz E.A., Potter J.D., Qi L., Rennert G., Sakoda L.C., Schafmayer C., Slattery M.L., Snetselaar L., Schenk J., Thibodeau S.N., Ulrich C.M., Van Guelpen B., Harlid S., Visvanathan K., Vodickova L., Wang H., White E., Wolk A., Woods M.O., Wu A.H., Zheng W., Bueno-de-Mesquita B., Boutron-Ruault M.-C., Hughes D.J., Jakszyn P., Kuhn T., Palli D., Riboli E., Giovannucci E.L., Banbury B.L., Gruber S.B., Peters U., Gunter M.J., Tsilidis K.K., Papadimitriou N., Dimou N., Gill D., Lewis S.J., Martin R.M., Murphy N., Burrows K., Lopez D.S., Key T.J., Travis R.C., Hampe J., Zuber V., Cross A.J., Perez-Cornago A., Hunter D.J., van Duijnhoven F.J.B., Albanes D., Arndt V., Berndt S.I., Bezieau S., Bishop D.T., Boehm J., Brenner H., Burnett-Hartman A., Campbell P.T., Casey G., Castellvi-Bel S., Chan A.T., Chang-Claude J., de la Chapelle A., Figueiredo J.C., Gallinger S.J., Giles G.G., Goodman P.J., Gsur A., Markozannes G., Hampel H., Hoffmeister M., Jenkins M.A., Keku T.O., Kweon S.-S., Larsson S.C., Le Marchand L., Li C.I., Li L., Lindblom A., Martin V., Milne R.L., Moreno V., Nan H., Nassir R., Newcomb P.A., Offit K., Pharoah P.D.P., Platz E.A., Potter J.D., Qi L., Rennert G., Sakoda L.C., Schafmayer C., Slattery M.L., Snetselaar L., Schenk J., Thibodeau S.N., Ulrich C.M., Van Guelpen B., Harlid S., Visvanathan K., Vodickova L., Wang H., White E., Wolk A., Woods M.O., Wu A.H., Zheng W., Bueno-de-Mesquita B., Boutron-Ruault M.-C., Hughes D.J., Jakszyn P., Kuhn T., Palli D., Riboli E., Giovannucci E.L., Banbury B.L., Gruber S.B., Peters U., Gunter M.J., Tsilidis K.K., Papadimitriou N., Dimou N., Gill D., Lewis S.J., Martin R.M., Murphy N., Burrows K., Lopez D.S., Key T.J., and Travis R.C.
- Abstract
BACKGROUND: The literature on associations of circulating concentrations of minerals and vitamins with risk of colorectal cancer is limited and inconsistent. Evidence from randomized controlled trials (RCTs) to support the efficacy of dietary modification or nutrient supplementation for colorectal cancer prevention is also limited. OBJECTIVE(S): To complement observational and RCT findings, we investigated associations of genetically predicted concentrations of 11 micronutrients (beta-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B-6, vitamin B-12, and zinc) with colorectal cancer risk using Mendelian randomization (MR). METHOD(S): Two-sample MR was conducted using 58,221 individuals with colorectal cancer and 67,694 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry. Inverse variance-weighted MR analyses were performed with sensitivity analyses to assess the impact of potential violations of MR assumptions. RESULT(S): Nominally significant associations were noted for genetically predicted iron concentration and higher risk of colon cancer [ORs per SD (ORSD): 1.08; 95% CI: 1.00, 1.17; P value=0.05] and similarly for proximal colon cancer, and for vitamin B-12 concentration and higher risk of colorectal cancer (ORSD: 1.12; 95% CI: 1.03, 1.21; P value=0.01) and similarly for colon cancer. A nominally significant association was also noted for genetically predicted selenium concentration and lower risk of colon cancer (ORSD: 0.98; 95% CI: 0.96, 1.00; P value=0.05) and similarly for distal colon cancer. These associations were robust to sensitivity analyses. Nominally significant inverse associations were observed for zinc and risk of colorectal and distal colon cancers, but sensitivity analyses could not be performed. None of these findings survived correction for multiple testing. Genetically predicted concentrations of beta-caroten
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- 2021
50. Salicylic acid and risk of colorectal cancer: A two-sample mendelian randomization study.
- Author
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Nounu A., Richmond R.C., Stewart I.D., Surendran P., Wareham N.J., Butterworth A., Weinstein S.J., Albanes D., Baron J.A., Hopper J.L., Figueiredo J.C., Newcomb P.A., Lindor N.M., Casey G., Platz E.A., Marchand L.L., Ulrich C.M., Li C.I., van Dujinhoven F.J.B., Gsur A., Campbell P.T., Moreno V., Vodicka P., Vodickova L., Amitay E., Alwers E., Chang-Claude J., Sakoda L.C., Slattery M.L., Schoen R.E., Gunter M.J., Castellvi-Bel S., Kim H.-R., Kweon S.-S., Chan A.T., Li L., Zheng W., Bishop D.T., Buchanan D.D., Giles G.G., Gruber S.B., Rennert G., Stadler Z.K., Harrison T.A., Lin Y., Keku T.O., Woods M.O., Schafmayer C., Van Guelpen B., Gallinger S., Hampel H., Berndt S.I., Pharoah P.D.P., Lindblom A., Wolk A., Wu A.H., White E., Peters U., Drew D.A., Scherer D., Bermejo J.L., Brenner H., Hoffmeister M., Williams A.C., Relton C.L., Nounu A., Richmond R.C., Stewart I.D., Surendran P., Wareham N.J., Butterworth A., Weinstein S.J., Albanes D., Baron J.A., Hopper J.L., Figueiredo J.C., Newcomb P.A., Lindor N.M., Casey G., Platz E.A., Marchand L.L., Ulrich C.M., Li C.I., van Dujinhoven F.J.B., Gsur A., Campbell P.T., Moreno V., Vodicka P., Vodickova L., Amitay E., Alwers E., Chang-Claude J., Sakoda L.C., Slattery M.L., Schoen R.E., Gunter M.J., Castellvi-Bel S., Kim H.-R., Kweon S.-S., Chan A.T., Li L., Zheng W., Bishop D.T., Buchanan D.D., Giles G.G., Gruber S.B., Rennert G., Stadler Z.K., Harrison T.A., Lin Y., Keku T.O., Woods M.O., Schafmayer C., Van Guelpen B., Gallinger S., Hampel H., Berndt S.I., Pharoah P.D.P., Lindblom A., Wolk A., Wu A.H., White E., Peters U., Drew D.A., Scherer D., Bermejo J.L., Brenner H., Hoffmeister M., Williams A.C., and Relton C.L.
- Abstract
Salicylic acid (SA) has observationally been shown to decrease colorectal cancer (CRC) risk. Aspirin (acetylsalicylic acid, that rapidly deacetylates to SA) is an effective primary and secondary chemopreventive agent. Through a Mendelian randomization (MR) approach, we aimed to address whether levels of SA affected CRC risk, stratifying by aspirin use. A two-sample MR analysis was performed using GWAS summary statistics of SA (INTERVAL and EPIC-Norfolk, N = 14,149) and CRC (CCFR, CORECT, GECCO and UK Biobank, 55,168 cases and 65,160 controls). The DACHS study (4410 cases and 3441 controls) was used for replication and stratification of aspirin use. SNPs proxying SA were selected via three methods: (1) functional SNPs that influence the activity of aspirin-metabolising enzymes; (2) pathway SNPs present in enzymes' coding regions; and (3) genome-wide significant SNPs. We found no association between functional SNPs and SA levels. The pathway and genome-wide SNPs showed no association between SA and CRC risk (OR:1.03, 95% CI: 0.84-1.27 and OR: 1.08, 95% CI:0.86-1.34, respectively). Results remained unchanged upon aspirin use stratification. We found little evidence to suggest that an SD increase in genetically predicted SA protects against CRC risk in the general population and upon stratification by aspirin use.Copyright © 2021 by the authors. Li-censee MDPI, Basel, Switzerland.
- Published
- 2021
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