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

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1. Menopausal status and factors affecting cessation of menses in the region of Bonn, Germany

Author: Pierl C., Rabstein S., Harth V., Brüning T., Brauch H., Fischer H., Hamann U., Justenhoven C., Ko Y., and Pesch B.
Subjects: allergy, cessation of menses, cox proportional hazard model, definition of menopausal status, hormone therapy, oral contraceptives, thyroidal medications, Medicine
Published: 2007
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2. Genetic variation in the immunosuppression pathway genes and breast cancer susceptibility: a pooled analysis of 42,510 cases and 40,577 controls from the Breast Cancer Association Consortium

Author: Lei, J, Rudolph, A, Moysich, KB, Behrens, S, Goode, EL, Bolla, MK, Dennis, J, Dunning, AM, Easton, DF, Wang, Q, Benitez, J, Hopper, JL, Southey, MC, Schmidt, MK, Broeks, A, Fasching, PA, Haeberle, L, Peto, J, dos-Santos-Silva, I, Sawyer, EJ, Tomlinson, I, Burwinkel, B, Marmé, F, Guénel, P, Truong, T, Bojesen, SE, Flyger, H, Nielsen, SF, Nordestgaard, BG, González-Neira, A, Menéndez, P, Anton-Culver, H, Neuhausen, SL, Brenner, H, Arndt, V, Meindl, A, Schmutzler, RK, Brauch, H, Hamann, U, Nevanlinna, H, Fagerholm, R, Dörk, T, Bogdanova, NV, Mannermaa, A, Hartikainen, JM, Australian Ovarian Study Group, kConFab Investigators, Van Dijck, L, Smeets, A, Flesch-Janys, D, Eilber, U, Radice, P, Peterlongo, P, Couch, FJ, Hallberg, E, Giles, GG, Milne, RL, Haiman, CA, Schumacher, F, Simard, J, Goldberg, MS, Kristensen, V, Borresen-Dale, AL, Zheng, W, Beeghly-Fadiel, A, Winqvist, R, Grip, M, Andrulis, IL, Glendon, G, García-Closas, M, Figueroa, J, Czene, K, Brand, JS, Darabi, H, Eriksson, M, Hall, P, Li, J, Cox, A, Cross, SS, Pharoah, PDP, Shah, M, Kabisch, M, Torres, D, Jakubowska, A, Lubinski, J, Ademuyiwa, F, Ambrosone, CB, Swerdlow, A, Jones, M, and Chang-Claude, J
Subjects: Genetics, Complementary and Alternative Medicine, Paediatrics and Reproductive Medicine, Genetics & Heredity
Abstract: Immunosuppression plays a pivotal role in assisting tumors to evade immune destruction and promoting tumor development. We hypothesized that genetic variation in the immunosuppression pathway genes may be implicated in breast cancer tumorigenesis. We included 42,510 female breast cancer cases and 40,577 controls of European ancestry from 37 studies in the Breast Cancer Association Consortium (2015) with available genotype data for 3595 single nucleotide polymorphisms (SNPs) in 133 candidate genes. Associations between genotyped SNPs and overall breast cancer risk, and secondarily according to estrogen receptor (ER) status, were assessed using multiple logistic regression models. Gene-level associations were assessed based on principal component analysis. Gene expression analyses were conducted using RNA sequencing level 3 data from The Cancer Genome Atlas for 989 breast tumor samples and 113 matched normal tissue samples. SNP rs1905339 (A>G) in the STAT3 region was associated with an increased breast cancer risk (per allele odds ratio 1.05, 95 % confidence interval 1.03–1.08; p value = 1.4 × 10−6). The association did not differ significantly by ER status. On the gene level, in addition to TGFBR2 and CCND1, IL5 and GM-CSF showed the strongest associations with overall breast cancer risk (p value = 1.0 × 10−3 and 7.0 × 10−3, respectively). Furthermore, STAT3 and IL5 but not GM-CSF were differentially expressed between breast tumor tissue and normal tissue (p value = 2.5 × 10−3, 4.5 × 10−4 and 0.63, respectively). Our data provide evidence that the immunosuppression pathway genes STAT3,IL5, and GM-CSF may be novel susceptibility loci for breast cancer in women of European ancestry.
Published: 2016

3. FGF receptor genes and breast cancer susceptibility: results from the Breast Cancer Association Consortium.

Author: Agarwal, D, Pineda, S, Michailidou, K, Herranz, J, Pita, G, Moreno, L, Alonso, M, Dennis, J, Wang, Q, Bolla, M, Meyer, K, Menéndez-Rodríguez, P, Hardisson, D, Mendiola, M, González-Neira, A, Lindblom, A, Margolin, S, Swerdlow, A, Orr, N, Jones, M, Matsuo, K, Ito, H, Iwata, H, Kondo, N, Hartman, M, Hui, M, Lim, W, Iau, P, Sawyer, E, Tomlinson, I, Kerin, M, Miller, N, Kang, D, Choi, J-Y, Park, S, Noh, D-Y, Hopper, J, Schmidt, D, Makalic, E, Southey, M, Teo, S, Yip, C, Sivanandan, K, Tay, W-T, Brauch, H, Brüning, T, Hamann, U, Dunning, A, Shah, M, Andrulis, I, Knight, J, Glendon, G, Tchatchou, S, Schmidt, M, Broeks, A, Rosenberg, E, vant Veer, L, Fasching, P, Renner, S, Ekici, A, Beckmann, M, Shen, C-Y, Hsiung, C-N, Yu, J-C, Hou, M-F, Blot, W, Cai, Q, Tseng, C-C, Van Den Berg, D, Stram, D, Cox, A, Brock, I, Reed, M, Muir, K, Lophatananon, A, Stewart-Brown, S, Siriwanarangsan, P, Zheng, W, Deming-Halverson, S, Shrubsole, M, Long, J, Shu, X-O, Lu, W, Gao, Y-T, Zhang, B, Radice, P, Peterlongo, P, Manoukian, S, Mariette, F, Sangrajrang, S, McKay, J, Couch, F, Toland, A, Yannoukakos, D, Fletcher, O, Johnson, N, dos Santos Silva, I, Peto, J, Marme, F, and Burwinkel, B
Subjects: Breast Neoplasms, Case-Control Studies, Female, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Genotype, Humans, Polymorphism, Single Nucleotide, Receptor, Fibroblast Growth Factor, Type 1, Receptor, Fibroblast Growth Factor, Type 2, Receptor, Fibroblast Growth Factor, Type 3, Receptor, Fibroblast Growth Factor, Type 4, Receptor, Fibroblast Growth Factor, Type 5
Abstract: BACKGROUND: Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium. METHODS: Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression. RESULTS: Little evidence of association with breast cancer risk was observed for SNPs in the FGF receptor genes. The strongest evidence in European women was for rs743682 in FGFR3; the estimated per-allele odds ratio was 1.05 (95% confidence interval=1.02-1.09, P=0.0020), which is substantially lower than that observed for SNPs in FGFR2. CONCLUSION: Our results suggest that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2.
Published: 2014

4. CYP2D6 Genotype and Adjuvant Tamoxifen: Meta‐Analysis of Heterogeneous Study Populations

Author: Province, MA, Goetz, MP, Brauch, H, Flockhart, DA, Hebert, JM, Whaley, R, Suman, VJ, Schroth, W, Winter, S, Zembutsu, H, Mushiroda, T, Newman, WG, Lee, M‐T M, Ambrosone, CB, Beckmann, MW, Choi, J‐Y, Dieudonné, A‐S, Fasching, PA, Ferraldeschi, R, Gong, L, Haschke‐Becher, E, Howell, A, Jordan, LB, Hamann, U, Kiyotani, K, Krippl, P, Lambrechts, D, Latif, A, Langsenlehner, U, Lorizio, W, Neven, P, Nguyen, AT, Park, B‐W, Purdie, CA, Quinlan, P, Renner, W, Schmidt, M, Schwab, M, Shin, J‐G, Stingl, JC, Wegman, P, Wingren, S, Wu, AHB, Ziv, E, Zirpoli, G, Thompson, AM, Jordan, VC, Nakamura, Y, Altman, RB, Ames, MM, Weinshilboum, RM, Eichelbaum, M, Ingle, JN, Klein, TE, and Consortium, International Tamoxifen Pharmacogenomics
Subjects: Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Breast Cancer, Women's Health, Estrogen, Aging, Cancer, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Aged, Antineoplastic Agents, Hormonal, Breast Neoplasms, Cytochrome P-450 CYP2D6, Female, Genetic Variation, Genotype, Humans, Menopause, Middle Aged, Pharmacogenetics, Survival Analysis, Tamoxifen, Treatment Outcome, International Tamoxifen Pharmacogenomics Consortium, Pharmacology & Pharmacy, Pharmacology and pharmaceutical sciences
Abstract: The International Tamoxifen Pharmacogenomics Consortium was established to address the controversy regarding cytochrome P450 2D6 (CYP2D6) status and clinical outcomes in tamoxifen therapy. We performed a meta-analysis on data from 4,973 tamoxifen-treated patients (12 globally distributed sites). Using strict eligibility requirements (postmenopausal women with estrogen receptor-positive breast cancer, receiving 20 mg/day tamoxifen for 5 years, criterion 1); CYP2D6 poor metabolizer status was associated with poorer invasive disease-free survival (IDFS: hazard ratio = 1.25; 95% confidence interval = 1.06, 1.47; P = 0.009). However, CYP2D6 status was not statistically significant when tamoxifen duration, menopausal status, and annual follow-up were not specified (criterion 2, n = 2,443; P = 0.25) or when no exclusions were applied (criterion 3, n = 4,935; P = 0.38). Although CYP2D6 is a strong predictor of IDFS using strict inclusion criteria, because the results are not robust to inclusion criteria (these were not defined a priori), prospective studies are necessary to fully establish the value of CYP2D6 genotyping in tamoxifen therapy.
Published: 2014

5. CYP2D6 Genotype and Adjuvant Tamoxifen: Meta-Analysis of Heterogeneous Study Populations

Author: Ziv, Elad, Wu, Alan, Province, MA, Goetz, MP, Brauch, H, Flockhart, DA, Hebert, JM, Whaley, R, Suman, VJ, Schroth, W, Winter, S, and Zembutsu, H
Abstract: The International Tamoxifen Pharmacogenomics Consortium was established to address the controversy regarding cytochrome P450 2D6 (CYP2D6) status and clinical outcomes in tamoxifen therapy. We performed a meta-analysis on data from 4,973 tamoxifen-treated p
Published: 2014

6. 9. Sicherheit und Schutz vor Krankheitserregern durch multiple Barrierensysteme

Author: Brauch, H.-J., primary, Werner, P., additional, Engel, W., additional, Petersohn, D., additional, Flemming, H.-C., additional, Wingender, J., additional, Schmidt, W., additional, and Schaefer, B., additional
Published: 2020
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7. Evidence of Gene-Environment Interactions between Common Breast Cancer Susceptibility Loci and Established Environmental Risk Factors

Author: Nickels, S, Truong, T, Hein, R, Stevens, K, Buck, K, Behrens, S, Eilber, U, Schmidt, M, Häberle, L, Vrieling, A, Gaudet, M, Figueroa, J, Schoof, N, Spurdle, AB, Rudolph, A, Fasching, PA, Hopper, JL, Makalic, E, Schmidt, DF, Southey, MC, Beckmann, MW, Ekici, AB, Fletcher, O, Gibson, L, dos Santos Silva, I, Peto, J, Humphreys, MK, Wang, J, Cordina-Duverger, E, Menegaux, F, Nordestgaard, BG, Bojesen, SE, Lanng, C, Anton-Culver, H, Ziogas, A, Bernstein, L, Clarke, CA, Brenner, H, Müller, H, Arndt, V, Stegmaier, C, Brauch, H, Brüning, T, Harth, V, Mannermaa, A, Kataja, V, Kosma, VM, Hartikainen, JM, Lambrechts, D, Smeets, D, Neven, P, Paridaens, R, Flesch-Janys, D, Obi, N, Wang-Gohrke, S, Couch, FJ, Olson, JE, Vachon, CM, Giles, GG, Severi, G, Baglietto, L, Offit, K, John, EM, Miron, A, Andrulis, IL, Knight, JA, Glendon, G, Mulligan, AM, Chanock, SJ, Lissowska, J, Liu, J, Cox, A, Cramp, H, Connley, D, Balasubramanian, S, Dunning, AM, Shah, M, Trentham-Dietz, A, Newcomb, P, Titus, L, Egan, K, Cahoon, EK, and Rajaraman, P
Abstract: Various common genetic susceptibility loci have been identified for breast cancer; however, it is unclear how they combine with lifestyle/environmental risk factors to influence risk. We undertook an international collaborative study to assess gene-environment interaction for risk of breast cancer. Data from 24 studies of the Breast Cancer Association Consortium were pooled. Using up to 34,793 invasive breast cancers and 41,099 controls, we examined whether the relative risks associated with 23 single nucleotide polymorphisms were modified by 10 established environmental risk factors (age at menarche, parity, breastfeeding, body mass index, height, oral contraceptive use, menopausal hormone therapy use, alcohol consumption, cigarette smoking, physical activity) in women of European ancestry. We used logistic regression models stratified by study and adjusted for age and performed likelihood ratio tests to assess gene-environment interactions. All statistical tests were two-sided. We replicated previously reported potential interactions between LSP1-rs3817198 and parity (Pinteraction= 2.4×10-6) and between CASP8-rs17468277 and alcohol consumption (Pinteraction= 3.1×10-4). Overall, the per-allele odds ratio (95% confidence interval) for LSP1-rs3817198 was 1.08 (1.01-1.16) in nulliparous women and ranged from 1.03 (0.96-1.10) in parous women with one birth to 1.26 (1.16-1.37) in women with at least four births. For CASP8-rs17468277, the per-allele OR was 0.91 (0.85-0.98) in those with an alcohol intake of
Published: 2013

8. Assessing interactions between the associations of common genetic susceptibility variants, reproductive history and body mass index with breast cancer risk in the breast cancer association consortium: A combined case-control study

Author: Milne, RL, Gaudet, MM, Spurdle, AB, Fasching, PA, Couch, FJ, Benítez, J, Arias Pérez, JI, Zamora, MP, Malats, N, dos Santos Silva, I, Gibson, LJ, Fletcher, O, Johnson, N, Anton-Culver, H, Ziogas, A, Figueroa, J, Brinton, L, Sherman, ME, Lissowska, J, Hopper, JL, Dite, GS, Apicella, C, Southey, MC, Sigurdson, AJ, Linet, MS, Schonfeld, SJ, Freedman, DM, Mannermaa, A, Kosma, VM, Kataja, V, Auvinen, P, Andrulis, IL, Glendon, G, Knight, JA, Weerasooriya, N, Cox, A, Reed, MWR, Cross, SS, Dunning, AM, Ahmed, S, Shah, M, Brauch, H, Ko, YD, Brüning, T, Lambrechts, D, Reumers, J, Smeets, A, Wang-Gohrke, S, Hall, P, Czene, K, Liu, J, Irwanto, AK, Chenevix-Trench, G, Holland, H, Fab, KC, Giles, GG, Baglietto, L, Severi, G, Bojensen, SE, Nordestgaard, BG, Flyger, H, John, EM, West, DW, Whittemore, AS, Vachon, C, Olson, JE, Fredericksen, Z, Kosel, M, Hein, R, Vrieling, A, Flesch-Janys, D, Heinz, J, Beckmann, MW, Heusinger, K, Ekici, AB, Haeberle, L, Humphreys, MK, Morrison, J, Easton, DF, and Pharoah, PD
Abstract: Introduction: Several common breast cancer genetic susceptibility variants have recently been identified. We aimed to determine how these variants combine with a subset of other known risk factors to influence breast cancer risk in white women of European ancestry using case-control studies participating in the Breast Cancer Association Consortium.Methods: We evaluated two-way interactions between each of age at menarche, ever having had a live birth, number of live births, age at first birth and body mass index (BMI) and each of 12 single nucleotide polymorphisms (SNPs) (10q26-rs2981582 (FGFR2), 8q24-rs13281615, 11p15-rs3817198 (LSP1), 5q11-rs889312 (MAP3K1), 16q12-rs3803662 (TOX3), 2q35-rs13387042, 5p12-rs10941679 (MRPS30), 17q23-rs6504950 (COX11), 3p24-rs4973768 (SLC4A7), CASP8-rs17468277, TGFB1-rs1982073 and ESR1-rs3020314). Interactions were tested for by fitting logistic regression models including per-allele and linear trend main effects for SNPs and risk factors, respectively, and single-parameter interaction terms for linear departure from independent multiplicative effects.Results: These analyses were applied to data for up to 26,349 invasive breast cancer cases and up to 32,208 controls from 21 case-control studies. No statistical evidence of interaction was observed beyond that expected by chance. Analyses were repeated using data from 11 population-based studies, and results were very similar.Conclusions: The relative risks for breast cancer associated with the common susceptibility variants identified to date do not appear to vary across women with different reproductive histories or body mass index (BMI). The assumption of multiplicative combined effects for these established genetic and other risk factors in risk prediction models appears justified. © 2010 Milne et al.; licensee BioMed Central Ltd.
Published: 2010

9. Environmental and Energy Security: Conceptual Evolution and Potential Applications to European Cross-Border Energy Supply Infrastructure

Author: Brauch, H. G., Culshaw, M.G., editor, Osipov, V.I., editor, Booth, S.J., editor, and Victorov, A.S., editor
Published: 2015
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10. Polymorphisms in genes of melatonin biosynthesis and signaling support the light-at-night hypothesis for breast cancer

Author: Wichert, K, Hoppe, R, Ickstadt, K, Behrens, T, Winter, S, Herold, R, Terschueren, C, Lo, W-Y, Guenel, P, Truong, T, Bolla, MK, Wang, Q, Dennis, J, Michailidou, K, Lush, M, Andrulis, IL, Brenner, H, Chang-Claude, J, Cox, A, Cross, SS, Czene, K, Eriksson, M, Figueroa, JD, Garcia-Closas, M, Goldberg, MS, Hamann, U, He, W, Holleczek, B, Hopper, JL, Jakubowska, A, Ko, Y-D, Lubinski, J, Mulligan, AM, Obi, N, Rhenius, V, Shah, M, Shu, X-O, Simard, J, Southey, MC, Zheng, W, Dunning, AM, Pharoah, PDP, Hall, P, Easton, DF, Bruening, T, Brauch, H, Harth, V, Rabstein, S, Wichert, K, Hoppe, R, Ickstadt, K, Behrens, T, Winter, S, Herold, R, Terschueren, C, Lo, W-Y, Guenel, P, Truong, T, Bolla, MK, Wang, Q, Dennis, J, Michailidou, K, Lush, M, Andrulis, IL, Brenner, H, Chang-Claude, J, Cox, A, Cross, SS, Czene, K, Eriksson, M, Figueroa, JD, Garcia-Closas, M, Goldberg, MS, Hamann, U, He, W, Holleczek, B, Hopper, JL, Jakubowska, A, Ko, Y-D, Lubinski, J, Mulligan, AM, Obi, N, Rhenius, V, Shah, M, Shu, X-O, Simard, J, Southey, MC, Zheng, W, Dunning, AM, Pharoah, PDP, Hall, P, Easton, DF, Bruening, T, Brauch, H, Harth, V, and Rabstein, S
Abstract: Light-at-night triggers the decline of pineal gland melatonin biosynthesis and secretion and is an IARC-classified probable breast-cancer risk factor. We applied a large-scale molecular epidemiology approach to shed light on the putative role of melatonin in breast cancer. We investigated associations between breast-cancer risk and polymorphisms at genes of melatonin biosynthesis/signaling using a study population of 44,405 women from the Breast Cancer Association Consortium (22,992 cases, 21,413 population-based controls). Genotype data of 97 candidate single nucleotide polymorphisms (SNPs) at 18 defined gene regions were investigated for breast-cancer risk effects. We calculated adjusted odds ratios (ORs) and 95% confidence intervals (CI) by logistic regression for the main-effect analysis as well as stratified analyses by estrogen- and progesterone-receptor (ER, PR) status. SNP-SNP interactions were analyzed via a two-step procedure based on logic regression. The Bayesian false-discovery probability (BFDP) was used for all analyses to account for multiple testing. Noteworthy associations (BFDP < 0.8) included 10 linked SNPs in tryptophan hydroxylase 2 (TPH2) (e.g. rs1386492: OR = 1.07, 95% CI 1.02-1.12), and a SNP in the mitogen-activated protein kinase 8 (MAPK8) (rs10857561: OR = 1.11, 95% CI 1.04-1.18). The SNP-SNP interaction analysis revealed noteworthy interaction terms with TPH2- and MAPK-related SNPs (e.g. rs1386483R ∧ rs1473473D ∧ rs3729931D: OR = 1.20, 95% CI 1.09-1.32). In line with the light-at-night hypothesis that links shift work with elevated breast-cancer risks our results point to SNPs in TPH2 and MAPK-genes that may impact the intricate network of circadian regulation.
Published: 2023

11. Association of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer-specific survival.

Author: Morra, A, Schreurs, MAC, Andrulis, IL, Anton-Culver, H, Augustinsson, A, Beckmann, MW, Behrens, S, Bojesen, SE, Bolla, MK, Brauch, H, Broeks, A, Buys, SS, Camp, NJ, Castelao, JE, Cessna, MH, Chang-Claude, J, Chung, WK, Collaborators, N, Colonna, SV, Couch, FJ, Cox, A, Cross, SS, Czene, K, Daly, MB, Dennis, J, Devilee, P, Dörk, T, Dunning, AM, Dwek, M, Easton, DF, Eccles, DM, Eriksson, M, Evans, DG, Fasching, PA, Fehm, TN, Figueroa, JD, Flyger, H, Gabrielson, M, Gago-Dominguez, M, García-Closas, M, García-Sáenz, JA, Genkinger, J, Grassmann, F, Gündert, M, Hahnen, E, Haiman, CA, Hamann, U, Harrington, PA, Hartikainen, JM, Hoppe, R, Hopper, JL, Houlston, RS, Howell, A, Investigators, A, Investigators, K, Jakubowska, A, Janni, W, Jernström, H, John, EM, Johnson, N, Jones, ME, Kristensen, VN, Kurian, AW, Lambrechts, D, Marchand, LL, Lindblom, A, Lubiński, J, Lux, MP, Mannermaa, A, Mavroudis, D, Mulligan, AM, Muranen, TA, Nevanlinna, H, Nevelsteen, I, Neven, P, Newman, WG, Obi, N, Offit, K, Olshan, AF, Park-Simon, T-W, Patel, AV, Peterlongo, P, Phillips, K-A, Plaseska-Karanfilska, D, Polley, EC, Presneau, N, Pylkäs, K, Rack, B, Radice, P, Rashid, MU, Rhenius, V, Robson, M, Romero, A, Saloustros, E, Sawyer, EJ, Schmutzler, RK, Schuetze, S, Scott, C, Shah, M, Smichkoska, S, Southey, MC, Tapper, WJ, Teras, LR, Tollenaar, RAEM, Tomczyk, K, Tomlinson, I, Troester, MA, Vachon, CM, van Veen, EM, Wang, Q, Wendt, C, Wildiers, H, Winqvist, R, Ziogas, A, Hall, P, Pharoah, PDP, Adank, MA, Hollestelle, A, Schmidt, MK, Hooning, MJ, Morra, A, Schreurs, MAC, Andrulis, IL, Anton-Culver, H, Augustinsson, A, Beckmann, MW, Behrens, S, Bojesen, SE, Bolla, MK, Brauch, H, Broeks, A, Buys, SS, Camp, NJ, Castelao, JE, Cessna, MH, Chang-Claude, J, Chung, WK, Collaborators, N, Colonna, SV, Couch, FJ, Cox, A, Cross, SS, Czene, K, Daly, MB, Dennis, J, Devilee, P, Dörk, T, Dunning, AM, Dwek, M, Easton, DF, Eccles, DM, Eriksson, M, Evans, DG, Fasching, PA, Fehm, TN, Figueroa, JD, Flyger, H, Gabrielson, M, Gago-Dominguez, M, García-Closas, M, García-Sáenz, JA, Genkinger, J, Grassmann, F, Gündert, M, Hahnen, E, Haiman, CA, Hamann, U, Harrington, PA, Hartikainen, JM, Hoppe, R, Hopper, JL, Houlston, RS, Howell, A, Investigators, A, Investigators, K, Jakubowska, A, Janni, W, Jernström, H, John, EM, Johnson, N, Jones, ME, Kristensen, VN, Kurian, AW, Lambrechts, D, Marchand, LL, Lindblom, A, Lubiński, J, Lux, MP, Mannermaa, A, Mavroudis, D, Mulligan, AM, Muranen, TA, Nevanlinna, H, Nevelsteen, I, Neven, P, Newman, WG, Obi, N, Offit, K, Olshan, AF, Park-Simon, T-W, Patel, AV, Peterlongo, P, Phillips, K-A, Plaseska-Karanfilska, D, Polley, EC, Presneau, N, Pylkäs, K, Rack, B, Radice, P, Rashid, MU, Rhenius, V, Robson, M, Romero, A, Saloustros, E, Sawyer, EJ, Schmutzler, RK, Schuetze, S, Scott, C, Shah, M, Smichkoska, S, Southey, MC, Tapper, WJ, Teras, LR, Tollenaar, RAEM, Tomczyk, K, Tomlinson, I, Troester, MA, Vachon, CM, van Veen, EM, Wang, Q, Wendt, C, Wildiers, H, Winqvist, R, Ziogas, A, Hall, P, Pharoah, PDP, Adank, MA, Hollestelle, A, Schmidt, MK, and Hooning, MJ
Abstract: Breast cancer (BC) patients with a germline CHEK2 c.1100delC variant have an increased risk of contralateral BC (CBC) and worse BC-specific survival (BCSS) compared to non-carriers. We aimed to assess the associations of CHEK2 c.1100delC, radiotherapy, and systemic treatment with CBC risk and BCSS. Analyses were based on 82,701 women diagnosed with invasive BC including 963 CHEK2 c.1100delC carriers; median follow-up was 9.1 years. Differential associations of treatment by CHEK2 c.1100delC status were tested by including interaction terms in a multivariable Cox regression model. A multi-state model was used for further insight into the relation between CHEK2 c.1100delC status, treatment, CBC risk and death. There was no evidence for differential associations of therapy with CBC risk by CHEK2 c.1100delC status The strongest association with reduced CBC risk was observed for the combination of chemotherapy and endocrine therapy [HR(95%CI): 0.66 (0.55-0.78)]. No association was observed with radiotherapy. Results from the multi-state model showed shorter BCSS for CHEK2 c.1100delC carriers versus non-carriers also after accounting for CBC occurrence [HR(95%CI) :1.30 (1.09-1.56)]. In conclusion, systemic therapy was associated with reduced CBC risk irrespective of CHEK2 c.1100delC status. Moreover, CHEK2 c.1100delC carriers had shorter BCSS, which appears not to be fully explained by their CBC risk. (Main MS: 3201 words).
Published: 2023

12. A genome-wide gene-environment interaction study of breast cancer risk for women of European ancestry

Author: Middha, PK, Wang, X, Behrens, S, Bolla, MK, Wang, Q, Dennis, J, Michailidou, K, Ahearn, TU, Andrulis, IL, Anton-Culver, H, Arndt, V, Aronson, KJ, Auer, PL, Augustinsson, A, Baert, T, Freeman, LEB, Becher, H, Beckmann, MW, Benitez, J, Bojesen, SE, Brauch, H, Brenner, H, Brooks-Wilson, A, Campa, D, Canzian, F, Carracedo, A, Castelao, JE, Chanock, SJ, Chenevix-Trench, G, Cordina-Duverger, E, Couch, FJ, Cox, A, Cross, SS, Czene, K, Dossus, L, Dugue, P-A, Eliassen, AH, Eriksson, M, Evans, DG, Fasching, PA, Figueroa, J, Fletcher, O, Flyger, H, Gabrielson, M, Gago-Dominguez, M, Giles, GG, Gonzalez-Neira, A, Grassmann, F, Grundy, A, Guenel, P, Haiman, CA, Hakansson, N, Hall, P, Hamann, U, Hankinson, SE, Harkness, EF, Holleczek, B, Hoppe, R, Hopper, JL, Houlston, RS, Howell, A, Hunter, DJ, Ingvar, C, Isaksson, K, Jernstroem, H, John, EM, Jones, ME, Kaaks, R, Keeman, R, Kitahara, CM, Ko, Y-D, Koutros, S, Kurian, AW, Lacey, JV, Lambrechts, D, Larson, NL, Larsson, S, Le Marchand, L, Lejbkowicz, F, Li, S, Linet, M, Lissowska, J, Martinez, ME, Maurer, T, Mulligan, AM, Mulot, C, Murphy, RA, Newman, WG, Nielsen, SF, Nordestgaard, BG, Norman, A, O'Brien, KM, Olson, JE, Patel, AV, Prentice, R, Rees-Punia, E, Rennert, G, Rhenius, V, Ruddy, KJ, Sandler, DP, Scott, CG, Shah, MT, Shu, X-O, Smeets, A, Southey, MC, Stone, J, Tamimi, RM, Taylor, JA, Teras, LR, Tomczyk, K, Troester, MA, Truong, T, Vachon, CM, Wang, SS, Weinberg, CR, Wildiers, H, Willett, W, Winham, SJ, Wolk, A, Yang, X, Zamora, MP, Zheng, W, Ziogas, A, Dunning, AM, Pharoah, PDP, Garcia-Closas, M, Schmidt, MK, Kraft, P, Milne, RL, Lindstroem, S, Easton, DF, Chang-Claude, J, Middha, PK, Wang, X, Behrens, S, Bolla, MK, Wang, Q, Dennis, J, Michailidou, K, Ahearn, TU, Andrulis, IL, Anton-Culver, H, Arndt, V, Aronson, KJ, Auer, PL, Augustinsson, A, Baert, T, Freeman, LEB, Becher, H, Beckmann, MW, Benitez, J, Bojesen, SE, Brauch, H, Brenner, H, Brooks-Wilson, A, Campa, D, Canzian, F, Carracedo, A, Castelao, JE, Chanock, SJ, Chenevix-Trench, G, Cordina-Duverger, E, Couch, FJ, Cox, A, Cross, SS, Czene, K, Dossus, L, Dugue, P-A, Eliassen, AH, Eriksson, M, Evans, DG, Fasching, PA, Figueroa, J, Fletcher, O, Flyger, H, Gabrielson, M, Gago-Dominguez, M, Giles, GG, Gonzalez-Neira, A, Grassmann, F, Grundy, A, Guenel, P, Haiman, CA, Hakansson, N, Hall, P, Hamann, U, Hankinson, SE, Harkness, EF, Holleczek, B, Hoppe, R, Hopper, JL, Houlston, RS, Howell, A, Hunter, DJ, Ingvar, C, Isaksson, K, Jernstroem, H, John, EM, Jones, ME, Kaaks, R, Keeman, R, Kitahara, CM, Ko, Y-D, Koutros, S, Kurian, AW, Lacey, JV, Lambrechts, D, Larson, NL, Larsson, S, Le Marchand, L, Lejbkowicz, F, Li, S, Linet, M, Lissowska, J, Martinez, ME, Maurer, T, Mulligan, AM, Mulot, C, Murphy, RA, Newman, WG, Nielsen, SF, Nordestgaard, BG, Norman, A, O'Brien, KM, Olson, JE, Patel, AV, Prentice, R, Rees-Punia, E, Rennert, G, Rhenius, V, Ruddy, KJ, Sandler, DP, Scott, CG, Shah, MT, Shu, X-O, Smeets, A, Southey, MC, Stone, J, Tamimi, RM, Taylor, JA, Teras, LR, Tomczyk, K, Troester, MA, Truong, T, Vachon, CM, Wang, SS, Weinberg, CR, Wildiers, H, Willett, W, Winham, SJ, Wolk, A, Yang, X, Zamora, MP, Zheng, W, Ziogas, A, Dunning, AM, Pharoah, PDP, Garcia-Closas, M, Schmidt, MK, Kraft, P, Milne, RL, Lindstroem, S, Easton, DF, and Chang-Claude, J
Abstract: BACKGROUND: Genome-wide studies of gene-environment interactions (G×E) may identify variants associated with disease risk in conjunction with lifestyle/environmental exposures. We conducted a genome-wide G×E analysis of ~ 7.6 million common variants and seven lifestyle/environmental risk factors for breast cancer risk overall and for estrogen receptor positive (ER +) breast cancer. METHODS: Analyses were conducted using 72,285 breast cancer cases and 80,354 controls of European ancestry from the Breast Cancer Association Consortium. Gene-environment interactions were evaluated using standard unconditional logistic regression models and likelihood ratio tests for breast cancer risk overall and for ER + breast cancer. Bayesian False Discovery Probability was employed to assess the noteworthiness of each SNP-risk factor pairs. RESULTS: Assuming a 1 × 10-5 prior probability of a true association for each SNP-risk factor pairs and a Bayesian False Discovery Probability < 15%, we identified two independent SNP-risk factor pairs: rs80018847(9p13)-LINGO2 and adult height in association with overall breast cancer risk (ORint = 0.94, 95% CI 0.92-0.96), and rs4770552(13q12)-SPATA13 and age at menarche for ER + breast cancer risk (ORint = 0.91, 95% CI 0.88-0.94). CONCLUSIONS: Overall, the contribution of G×E interactions to the heritability of breast cancer is very small. At the population level, multiplicative G×E interactions do not make an important contribution to risk prediction in breast cancer.
Published: 2023

13. Clinical outcome and global gene expression data support the existence of the estrogen receptor-negative/progesterone receptor-positive invasive breast cancer phenotype

Author: Schroth, Werner, Winter, S., Büttner, F., Goletz, S., Faißt, S., Brinkmann, F., Saladores, P., Heidemann, E., Ott, G., Gerteis, A., Alscher, M. D., Dippon, J., Schwab, M., Brauch, H., and Fritz, P.
Published: 2016
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14. Breast Cancer Risk Genes — Association Analysis in More than 113,000 Women

Author: Dorling, L., Carvalho, S., Allen, J., Gonzalez-Neira, A., Luccarini, C., Wahlstrom, C., Pooley, K.A., Parsons, M.T., Fortuno, C., Wang, Q., Bolla, M.K., Dennis, J., Keeman, R., Alonso, M.R., Alvarez, N., Herraez, B., Fernandez, V., Nunez-Torres, R., Osorio, A., Valcich, J., Li, M., Torngren, T., Harrington, P.A., Baynes, C., Conroy, D.M., Decker, B., Fachal, L., Mavaddat, N., Ahearn, T., Aittomaki, K., Antonenkova, N.N., Arnold, N., Arveux, P., Ausems, M.G.E.M., Auvinen, P., Becher, H., Beckmann, M.W., Behrens, S., Bermisheva, M., Bialkowska, K., Blomqvist, C., Bogdanova, N.V., Bogdanova-Markov, N., Bojesen, S.E., Bonanni, B., Borresen-Dale, A.L., Brauch, H., Bremer, M., Briceno, I., Bruning, T., Burwinkel, B., Cameron, D.A., Camp, N.J., Campbell, A., Carracedo, A., Castelao, J.E., Cessna, M.H., Chanock, S.J., Christiansen, H., Collee, J.M., Cordina-Duverger, E., Cornelissen, S., Czene, K., Dork, T., Ekici, A.B., Engel, C., Eriksson, M., Fasching, P.A., Figueroa, J., Flyger, H., Forsti, A., Gabrielson, M., Gago-Dominguez, M., Georgoulias, V., Gil, F., Giles, G.G., Glendon, G., Garcia, E.B.G., Alnaes, G.I.G., Guenel, P., Hadjisavvas, A., Haeberle, L., Hahnen, E., Hall, P., Hamann, U., Harkness, E.F., Hartikainen, J.M., Hartman, M., He, W., Heemskerk-Gerritsen, B.A.M., Hillemanns, P., Hogervorst, F.B.L., Hollestelle, A., Ho, W.K., Hooning, M.J., Howell, A., Humphreys, K., Idris, F., Jakubowska, A., Jung, A., Kapoor, P.M., Kerin, M.J., Khusnutdinova, E., Kim, S.W., Ko, Y.D., Kosma, V.M., Kristensen, V.N., Kyriacou, K., Lakeman, I.M.M., Lee, J.W., Lee, M.H., Li, J.M., Lindblom, A., W.Y. lo, Loizidou, M.A., Lophatananon, A., Lubinski, J., MacInnis, R.J., Madsen, M.J., Mannermaa, A., Manoochehri, M., Manoukian, S., Margolin, S., Martinez, M.E., Maurer, T., Mavroudis, D., McLean, C., Meindl, A., Mensenkamp, A.R., Michailidou, K., Miller, N., Taib, N.A.M., Muir, K., Mulligan, A.M., Nevanlinna, H., Newman, W.G., Nordestgaard, B.G., Ng, P.S., Oosterwijk, J.C., Park, S.K., Park-Simon, T.W., Perez, J.I.A., Peterlongo, P., Porteous, D.J., Prajzendanc, K., Prokofyeva, D., Radice, P., Rashid, M.U., Rhenius, V., Rookus, M.A., Rudiger, T., Saloustros, E., Sawyer, E.J., Schmutzler, R.K., Schneeweiss, A., Schurmann, P., Shah, M., Sohn, C., Southey, M.C., Surowy, H., Suvanto, M., Thanasitthichai, S., Tomlinson, I., Torres, D., Truong, T., Tzardi, M., Valova, Y., Asperen, C.J. van, Dam, R.M. van, Ouweland, A.M.W. van den, Kolk, L.E. van der, Veen, E.M. van, Wendt, C., Williams, J.A., Yang, X.H.R., Yoon, S.Y., Zamora, M.P., Evans, D.G., Hoya, M. de la, Simard, J., Antoniou, A.C., Borg, A., Andrulis, I.L., Chang-Claude, J., Garcia-Closas, M., Chenevix-Trench, G., Milne, R.L., Pharoah, P.D.P., Schmidt, M.K., Spurdle, A.B., Vreeswijk, M.P.G., Benitez, J., Dunning, A.M., Kvist, A., Teo, S.H., Devilee, P., Easton, D.F., Breast Canc Assoc Consortium, Erasmus MC other, Medical Oncology, Clinical Genetics, Keeman, Renske [0000-0002-5452-9933], Decker, Brennan [0000-0003-4516-7421], Eriksson, Mikael [0000-0001-8135-4270], Martinez, Maria Elena [0000-0002-6728-1834], Surowy, Harald [0000-0002-3595-9188], Pharoah, Paul DP [0000-0001-8494-732X], Apollo - University of Cambridge Repository, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Targeted Gynaecologic Oncology (TARGON), RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: DA KG Polikliniek (9), and Klinische Genetica
Subjects: Adult, Risk, Oncology, medicine.medical_specialty, Adolescent, PALB2, Genetic counseling, Genes, BRCA2, Mutation, Missense, Genes, BRCA1, Estrogen receptor, Breast Neoplasms, 030204 cardiovascular system & hematology, OVARIAN-CANCER, Article, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, SDG 3 - Good Health and Well-being, Internal medicine, Odds Ratio, medicine, Humans, Genetic Predisposition to Disease, 030212 general & internal medicine, skin and connective tissue diseases, CHEK2, Aged, Genetic testing, Genetic association, Aged, 80 and over, Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17], medicine.diagnostic_test, MUTATIONS, business.industry, Age Factors, Genetic Variation, Sequence Analysis, DNA, General Medicine, Odds ratio, Middle Aged, BRCA1, medicine.disease, 3. Good health, Logistic Models, Female, business
Abstract: BACKGROUNDGenetic testing for breast cancer susceptibility is widely used, but for many genes,evidence of an association with breast cancer is weak, underlying risk estimatesare imprecise, and reliable subtype-specific risk estimates are lacking.METHODSWe used a panel of 34 putative susceptibility genes to perform sequencing onsamples from 60,466 women with breast cancer and 53,461 controls. In separateanalyses for protein-truncating variants and rare missense variants in these genes,we estimated odds ratios for breast cancer overall and tumor subtypes. We evaluatedmissense-variant associations according to domain and classification of pathogenicity.RESULTSProtein-truncating variants in 5 genes (ATM, BRCA1, BRCA2, CHEK2, and PALB2)were associated with a risk of breast cancer overall with a P value of less than0.0001. Protein-truncating variants in 4 other genes (BARD1, RAD51C, RAD51D,and TP53) were associated with a risk of breast cancer overall with a P value ofless than 0.05 and a Bayesian false-discovery probability of less than 0.05. Forprotein-truncating variants in 19 of the remaining 25 genes, the upper limit ofthe 95% confidence interval of the odds ratio for breast cancer overall was lessthan 2.0. For protein-truncating variants in ATM and CHEK2, odds ratios werehigher for estrogen receptor (ER)–positive disease than for ER-negative disease;for protein-truncating variants in BARD1, BRCA1, BRCA2, PALB2, RAD51C, andRAD51D, odds ratios were higher for ER-negative disease than for ER-positivedisease. Rare missense variants (in aggregate) in ATM, CHEK2, and TP53 wereassociated with a risk of breast cancer overall with a P value of less than 0.001.For BRCA1, BRCA2, and TP53, missense variants (in aggregate) that would be classified as pathogenic according to standard criteria were associated with a riskof breast cancer overall, with the risk being similar to that of protein-truncatingvariants.CONCLUSIONSThe results of this study define the genes that are most clinically useful for inclusion on panels for the prediction of breast cancer risk, as well as provide estimatesof the risks associated with protein-truncating variants, to guide genetic counseling. (Funded by European Union Horizon 2020 programs and others.)
Published: 2021

15. Common variants in breast cancer risk loci predispose to distinct tumor subtypes

Author: 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.
Published: 2022

16. Common variants in breast cancer risk loci predispose to distinct tumor subtypes

Author: 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.
Published: 2022

17. p53-Alterations in Thymic Epithelial Tumors

Author: Weirich, G., Schneider, P., Fellbaum, C., Brauch, H., Nathrath, W., Scholz, M., Präuer, H., Höfler, H., Marx, Alexander, editor, and Müller-Hermelink, Hans Konrad, editor
Published: 1997
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18. Models and Predictability of the Micropollutant Removal by Adsorption on Activated Carbon

Author: Haist-Gulde, B., Baldauf, G., Brauch, H.-J., Hutzinger, Otto, editor, and Hrubec, Jiri, editor
Published: 1995
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19. Removal of Organic Micropollutants by Activated Carbon

Author: Haist-Gulde, B., Baldauf, G., Brauch, H.-J., Hutzinger, Otto, editor, and Hrubec, Jiri, editor
Published: 1995
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20. Molecular Analysis of Different Loci on Chromosomes 3, 5, and 17 in Sporadic Renal Cell Carcinoma

Author: Brauch, H., Schadt, T., Hieronymus, T., Komitowski, D., Pomer, S., Staehler, Gerd, editor, and Pomer, Sigmund, editor
Published: 1994
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21. Fate of the Antidiabetic Drug Metformin During Chlorine Disinfection of Water

Author: Armbruster, D., primary, Happel, O., additional, Scheurer, M., additional, Harms, K., additional, Schmidt, T. C., additional, and Brauch, H.-J., additional
Published: 2015
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22. Molecular Analysis of DNA Sequences on Chromosome 3 in Patients with Renal Cell Carcinoma

Author: Brauch, H., Tory, K., Hosoe, S., Anglard, P., Lerman, M., Linehan, M., Zbar, B., Staehler, Gerd, editor, and Pomer, Sigmund, editor
Published: 1992
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23. Tamoxifen metabolism predicts drug concentrations and outcome in premenopausal patients with early breast cancer

Author: Saladores, P, Mürdter, T, Eccles, D, Chowbay, B, Zgheib, N K, Winter, S, Ganchev, B, Eccles, B, Gerty, S, Tfayli, A, Lim, J SL, Yap, Y S, Ng, R CH, Wong, N S, Dent, R, Habbal, M Z, Schaeffeler, E, Eichelbaum, M, Schroth, W, Schwab, M, and Brauch, H
Published: 2015
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24. Environmental and Energy Security: Conceptual Evolution and Potential Applications to European Cross-Border Energy Supply Infrastructure

Author: Brauch, H. G., primary
Published: 2014
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25. Charakterisierung von Keimbahnmutationen bei Patienten mit familiärer adenomatöser Polyposis (FAP) durch DNA-Sequenzanalyse

Author: Hahn, M., Lamadé, W., Gebert, J., Kadmon, M., Brauch, H., Herfarth, Ch., Schackert, H. K., and Beger, Hans G., editor
Published: 1994
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26. CYP3A7*1C allele:linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers

Author: 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.
Published: 2021

27. Mendelian randomisation study of smoking exposure in relation to breast cancer risk

Author: 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
Subjects: 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.
Published: 2021

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

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

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

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

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

31. Mendelian randomisation study of smoking exposure in relation to breast cancer risk.

Author: 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

32. Breast cancer risk genes - Association analysis in more than 113,000 women.

Author: Cornelissen S., Michailidou K., Miller N., Taib N.A.M., Muir K., Mulligan A.M., Nevanlinna H., Newman W.G., Nordestgaard B.G., Ng P.-S., Oosterwijk J.C., Park S.K., Park-Simon T.-W., Perez J.I.A., Peterlongo P., Porteous D.J., Prajzendanc K., Prokofyeva D., Radice P., Rashid M.U., Rhenius V., Rookus M.A., Rudiger T., Saloustros E., Sawyer E.J., Schmutzler R.K., Schneeweiss A., Schurmann P., Shah M., Sohn C., Southey M.C., Surowy H., Suvanto M., Thanasitthichai S., Tomlinson I., Torres D., Truong T., Tzardi M., Valova Y., van Asperen C.J., van Dam R.M., van den Ouweland A.M.W., van der Kolk L.E., van Veen E.M., Wendt C., Williams J.A., Yang X.R., Yoon S.-Y., Zamora M.P., Evans D.G., de la Hoya M., Simard J., Antoniou A.C., Borg A., Andrulis I.L., Chang-Claude J., Garcia-Closas M., Chenevix-Trench G., Milne R.L., Pharoah P.D.P., Schmidt M.K., Spurdle A.B., Vreeswijk M.P.G., Benitez J., Dunning A.M., Kvist A., Teo S.H., Devilee P., Easton D.F., Dorling L., Carvalho S., Allen J., Gonzalez-Neira A., Luccarini C., Wahlstrom C., Pooley K.A., Parsons M.T., Fortuno C., Wang Q., Bolla M.K., Dennis J., Keeman R., Alonso M.R., Alvarez N., Herraez B., Fernandez V., Nunez-Torres R., Osorio A., Valcich J., Li M., Torngren T., Harrington P.A., Baynes C., Conroy D.M., Decker B., Fachal L., Mavaddat N., Ahearn T., Aittomaki K., Antonenkova N.N., Arnold N., Arveux P., Ausems M.G.E.M., Auvinen P., Becher H., Beckmann M.W., Behrens S., Bermisheva M., Bialkowska K., Blomqvist C., Bogdanova N.V., Bogdanova-Markov N., Bojesen S.E., Bonanni B., Borresen-Dale A.-L., Brauch H., Bremer M., Briceno I., Bruning T., Burwinkel B., Cameron D.A., Camp N.J., Campbell A., Carracedo A., Castelao J.E., Cessna M.H., Chanock S.J., Christiansen H., Collee J.M., Cordina-Duverger E., Czene K., Dork T., Ekici A.B., Engel C., Eriksson M., Fasching P.A., Figueroa J., Flyger H., Forsti A., Gabrielson M., Gago-Dominguez M., Georgoulias V., Gil F., Giles G.G., Glendon G., Gomez Garcia E.B., Grenaker Alnaes G.I., Guenel P., Hadjisavvas A., Haeberle L., Hahnen E., Hall P., Hamann U., Harkness E.F., Hartikainen J.M., Hartman M., He W., Heemskerk-Gerritsen B.A.M., Hillemanns P., Hogervorst F.B.L., Hollestelle A., Ho W.K., Hooning M.J., Howell A., Humphreys K., Idris F., Jakubowska A., Jung A., Kapoor P.M., Kerin M.J., Khusnutdinova E., Kim S.-W., Ko Y.-D., Kosma V.-M., Kristensen V.N., Kyriacou K., Lakeman I.M.M., Lee J.W., Lee M.H., Li J., Lindblom A., Lo W.-Y., Loizidou M.A., Lophatananon A., Lubinski J., MacInnis R.J., Madsen M.J., Mannermaa A., Manoochehri M., Manoukian S., Margolin S., Martinez M.E., Maurer T., Mavroudis D., McLean C., Meindl A., Mensenkamp A.R., Cornelissen S., Michailidou K., Miller N., Taib N.A.M., Muir K., Mulligan A.M., Nevanlinna H., Newman W.G., Nordestgaard B.G., Ng P.-S., Oosterwijk J.C., Park S.K., Park-Simon T.-W., Perez J.I.A., Peterlongo P., Porteous D.J., Prajzendanc K., Prokofyeva D., Radice P., Rashid M.U., Rhenius V., Rookus M.A., Rudiger T., Saloustros E., Sawyer E.J., Schmutzler R.K., Schneeweiss A., Schurmann P., Shah M., Sohn C., Southey M.C., Surowy H., Suvanto M., Thanasitthichai S., Tomlinson I., Torres D., Truong T., Tzardi M., Valova Y., van Asperen C.J., van Dam R.M., van den Ouweland A.M.W., van der Kolk L.E., van Veen E.M., Wendt C., Williams J.A., Yang X.R., Yoon S.-Y., Zamora M.P., Evans D.G., de la Hoya M., Simard J., Antoniou A.C., Borg A., Andrulis I.L., Chang-Claude J., Garcia-Closas M., Chenevix-Trench G., Milne R.L., Pharoah P.D.P., Schmidt M.K., Spurdle A.B., Vreeswijk M.P.G., Benitez J., Dunning A.M., Kvist A., Teo S.H., Devilee P., Easton D.F., Dorling L., Carvalho S., Allen J., Gonzalez-Neira A., Luccarini C., Wahlstrom C., Pooley K.A., Parsons M.T., Fortuno C., Wang Q., Bolla M.K., Dennis J., Keeman R., Alonso M.R., Alvarez N., Herraez B., Fernandez V., Nunez-Torres R., Osorio A., Valcich J., Li M., Torngren T., Harrington P.A., Baynes C., Conroy D.M., Decker B., Fachal L., Mavaddat N., Ahearn T., Aittomaki K., Antonenkova N.N., Arnold N., Arveux P., Ausems M.G.E.M., Auvinen P., Becher H., Beckmann M.W., Behrens S., Bermisheva M., Bialkowska K., Blomqvist C., Bogdanova N.V., Bogdanova-Markov N., Bojesen S.E., Bonanni B., Borresen-Dale A.-L., Brauch H., Bremer M., Briceno I., Bruning T., Burwinkel B., Cameron D.A., Camp N.J., Campbell A., Carracedo A., Castelao J.E., Cessna M.H., Chanock S.J., Christiansen H., Collee J.M., Cordina-Duverger E., Czene K., Dork T., Ekici A.B., Engel C., Eriksson M., Fasching P.A., Figueroa J., Flyger H., Forsti A., Gabrielson M., Gago-Dominguez M., Georgoulias V., Gil F., Giles G.G., Glendon G., Gomez Garcia E.B., Grenaker Alnaes G.I., Guenel P., Hadjisavvas A., Haeberle L., Hahnen E., Hall P., Hamann U., Harkness E.F., Hartikainen J.M., Hartman M., He W., Heemskerk-Gerritsen B.A.M., Hillemanns P., Hogervorst F.B.L., Hollestelle A., Ho W.K., Hooning M.J., Howell A., Humphreys K., Idris F., Jakubowska A., Jung A., Kapoor P.M., Kerin M.J., Khusnutdinova E., Kim S.-W., Ko Y.-D., Kosma V.-M., Kristensen V.N., Kyriacou K., Lakeman I.M.M., Lee J.W., Lee M.H., Li J., Lindblom A., Lo W.-Y., Loizidou M.A., Lophatananon A., Lubinski J., MacInnis R.J., Madsen M.J., Mannermaa A., Manoochehri M., Manoukian S., Margolin S., Martinez M.E., Maurer T., Mavroudis D., McLean C., Meindl A., and Mensenkamp A.R.
Abstract: BACKGROUND Genetic testing for breast cancer susceptibility is widely used, but for many genes, evidence of an association with breast cancer is weak, underlying risk estimates are imprecise, and reliable subtype-specific risk estimates are lacking. METHODS We used a panel of 34 putative susceptibility genes to perform sequencing on samples from 60,466 women with breast cancer and 53,461 controls. In separate analyses for protein-truncating variants and rare missense variants in these genes, we estimated odds ratios for breast cancer overall and tumor subtypes. We evaluated missense-variant associations according to domain and classification of pathogenicity. RESULTS Protein-truncating variants in 5 genes (ATM, BRCA1, BRCA2, CHEK2, and PALB2) were associated with a risk of breast cancer overall with a P value of less than 0.0001. Protein-truncating variants in 4 other genes (BARD1, RAD51C, RAD51D, and TP53) were associated with a risk of breast cancer overall with a P value of less than 0.05 and a Bayesian false-discovery probability of less than 0.05. For protein-truncating variants in 19 of the remaining 25 genes, the upper limit of the 95% confidence interval of the odds ratio for breast cancer overall was less than 2.0. For protein-truncating variants in ATM and CHEK2, odds ratios were higher for estrogen receptor (ER)-positive disease than for ER-negative disease; for protein-truncating variants in BARD1, BRCA1, BRCA2, PALB2, RAD51C, and RAD51D, odds ratios were higher for ER-negative disease than for ER-positive disease. Rare missense variants (in aggregate) in ATM, CHEK2, and TP53 were associated with a risk of breast cancer overall with a P value of less than 0.001. For BRCA1, BRCA2, and TP53, missense variants (in aggregate) that would be classified as pathogenic according to standard criteria were associated with a risk of breast cancer overall, with the risk being similar to that of protein-truncating variants. CONCLUSIONS The results of this study define
Published: 2021

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

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

34. CYP3A7*1C allele: linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers.

Author: 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).
Published: 2021

35. Combined Associations of a Polygenic Risk Score and Classical Risk Factors with Breast Cancer Risk.

Author: 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

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

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

37. Association of germline genetic variants with breast cancer-specific survival in patient subgroups defined by clinic-pathological variables related to tumor biology and type of systemic treatment.

Author: Morra A., Escala-Garcia M., Beesley J., Keeman R., Canisius S., Ahearn T.U., Andrulis I.L., Anton-Culver H., Arndt V., Auer P.L., Augustinsson A., Beane Freeman L.E., Becher H., Beckmann M.W., Behrens S., Bojesen S.E., Bolla M.K., Brenner H., Bruning T., Buys S.S., Caan B., Campa D., Canzian F., Castelao J.E., Chang-Claude J., Chanock S.J., Cheng T.-Y.D., Clarke C.L., Colonna S.V., Couch F.J., Cox A., Cross S.S., Czene K., Daly M.B., Dennis J., Dork T., Dossus L., Dunning A.M., Dwek M., Eccles D.M., Ekici A.B., Eliassen A.H., Eriksson M., Evans D.G., Fasching P.A., Flyger H., Fritschi L., Gago-Dominguez M., Garcia-Saenz J.A., Giles G.G., Grip M., Guenel P., Gundert M., Hahnen E., Haiman C.A., Hakansson N., Hall P., Hamann U., Hart S.N., Hartikainen J.M., Hartmann A., He W., Hooning M.J., Hoppe R., Hopper J.L., Howell A., Hunter D.J., Jager A., Jakubowska A., Janni W., John E.M., Jung A.Y., Kaaks R., Keupers M., Kitahara C.M., Koutros S., Kraft P., Kristensen V.N., Kurian A.W., Lacey J.V., Lambrechts D., Le Marchand L., Lindblom A., Linet M., Luben R.N., Lubinski J., Lush M., Mannermaa A., Manoochehri M., Margolin S., Martens J.W.M., Martinez M.E., Mavroudis D., Michailidou K., Milne R.L., Mulligan A.M., Muranen T.A., Nevanlinna H., Newman W.G., Nielsen S.F., Nordestgaard B.G., Olshan A.F., Olsson H., Orr N., Park-Simon T.-W., Patel A.V., Peissel B., Peterlongo P., Plaseska-Karanfilska D., Prajzendanc K., Prentice R., Presneau N., Rack B., Rennert G., Rennert H.S., Rhenius V., Romero A., Roylance R., Ruebner M., Saloustros E., Sawyer E.J., Schmutzler R.K., Schneeweiss A., Scott C., Shah M., Smichkoska S., Southey M.C., Stone J., Surowy H., Swerdlow A.J., Tamimi R.M., Tapper W.J., Teras L.R., Terry M.B., Tollenaar R.A.E.M., Tomlinson I., Troester M.A., Truong T., Vachon C.M., Wang Q., Hurson A.N., Winqvist R., Wolk A., Ziogas A., Brauch H., Garcia-Closas M., Pharoah P.D.P., Easton D.F., Chenevix-Trench G., Schmidt M.K., Morra A., Escala-Garcia M., Beesley J., Keeman R., Canisius S., Ahearn T.U., Andrulis I.L., Anton-Culver H., Arndt V., Auer P.L., Augustinsson A., Beane Freeman L.E., Becher H., Beckmann M.W., Behrens S., Bojesen S.E., Bolla M.K., Brenner H., Bruning T., Buys S.S., Caan B., Campa D., Canzian F., Castelao J.E., Chang-Claude J., Chanock S.J., Cheng T.-Y.D., Clarke C.L., Colonna S.V., Couch F.J., Cox A., Cross S.S., Czene K., Daly M.B., Dennis J., Dork T., Dossus L., Dunning A.M., Dwek M., Eccles D.M., Ekici A.B., Eliassen A.H., Eriksson M., Evans D.G., Fasching P.A., Flyger H., Fritschi L., Gago-Dominguez M., Garcia-Saenz J.A., Giles G.G., Grip M., Guenel P., Gundert M., Hahnen E., Haiman C.A., Hakansson N., Hall P., Hamann U., Hart S.N., Hartikainen J.M., Hartmann A., He W., Hooning M.J., Hoppe R., Hopper J.L., Howell A., Hunter D.J., Jager A., Jakubowska A., Janni W., John E.M., Jung A.Y., Kaaks R., Keupers M., Kitahara C.M., Koutros S., Kraft P., Kristensen V.N., Kurian A.W., Lacey J.V., Lambrechts D., Le Marchand L., Lindblom A., Linet M., Luben R.N., Lubinski J., Lush M., Mannermaa A., Manoochehri M., Margolin S., Martens J.W.M., Martinez M.E., Mavroudis D., Michailidou K., Milne R.L., Mulligan A.M., Muranen T.A., Nevanlinna H., Newman W.G., Nielsen S.F., Nordestgaard B.G., Olshan A.F., Olsson H., Orr N., Park-Simon T.-W., Patel A.V., Peissel B., Peterlongo P., Plaseska-Karanfilska D., Prajzendanc K., Prentice R., Presneau N., Rack B., Rennert G., Rennert H.S., Rhenius V., Romero A., Roylance R., Ruebner M., Saloustros E., Sawyer E.J., Schmutzler R.K., Schneeweiss A., Scott C., Shah M., Smichkoska S., Southey M.C., Stone J., Surowy H., Swerdlow A.J., Tamimi R.M., Tapper W.J., Teras L.R., Terry M.B., Tollenaar R.A.E.M., Tomlinson I., Troester M.A., Truong T., Vachon C.M., Wang Q., Hurson A.N., Winqvist R., Wolk A., Ziogas A., Brauch H., Garcia-Closas M., Pharoah P.D.P., Easton D.F., Chenevix-Trench G., and Schmidt M.K.
Abstract: BACKGROUND: Given the high heterogeneity among breast tumors, associations between common germline genetic variants and survival that may exist within specific subgroups could go undetected in an unstratified set of breast cancer patients. METHOD(S): We performed genome-wide association analyses within 15 subgroups of breast cancer patients based on prognostic factors, including hormone receptors, tumor grade, age, and type of systemic treatment. Analyses were based on 91,686 female patients of European ancestry from the Breast Cancer Association Consortium, including 7531 breast cancer-specific deaths over a median follow-up of 8.1years. Cox regression was used to assess associations of common germline variants with 15-year and 5-year breast cancer-specific survival. We assessed the probability of these associations being true positives via the Bayesian false discovery probability (BFDP <0.15). RESULT(S): Evidence of associations with breast cancer-specific survival was observed in three patient subgroups, with variant rs5934618 in patients with grade 3 tumors (15-year-hazard ratio (HR) [95% confidence interval (CI)] 1.32 [1.20, 1.45], P = 1.4E-08, BFDP = 0.01, per G allele); variant rs4679741 in patients with ER-positive tumors treated with endocrine therapy (15-year-HR [95% CI] 1.18 [1.11, 1.26], P = 1.6E-07, BFDP = 0.09, per G allele); variants rs1106333 (15-year-HR [95% CI] 1.68 [1.39,2.03], P = 5.6E-08, BFDP = 0.12, per A allele) and rs78754389 (5-year-HR [95% CI] 1.79 [1.46,2.20], P = 1.7E-08, BFDP = 0.07, per A allele), in patients with ER-negative tumors treated with chemotherapy. CONCLUSION(S): We found evidence of four loci associated with breast cancer-specific survival within three patient subgroups. There was limited evidence for the existence of associations in other patient subgroups. However, the power for many subgroups is limited due to the low number of events. Even so, our results suggest that the impact of common germline genetic variants on br
Published: 2021

38. Combined Associations of a Polygenic Risk Score and Classical Risk Factors With Breast Cancer Risk

Author: Kapoor, PM, Mavaddat, N, Choudhury, PP, Wilcox, AN, Lindstrom, S, Behrens, S, Michailidou, K, Dennis, J, Bolla, MK, Wang, Q, Jung, A, Abu-Ful, Z, Ahearn, T, Andrulis, IL, Anton-Culver, H, Arndt, V, Aronson, KJ, Auer, PL, Freeman, LEB, Becher, H, Beckmann, MW, Beeghly-Fadiel, A, Benitez, J, Bernstein, L, Bojesen, SE, Brauch, H, Brenner, H, Bruening, T, Cai, Q, Campa, D, Canzian, F, Carracedo, A, Carter, BD, Castelao, JE, Chanock, SJ, Chatterjee, N, Chenevix-Trench, G, Clarke, CL, Couch, FJ, Cox, A, Cross, SS, Czene, K, Dai, JY, Earp, HS, Ekici, AB, Eliassen, AH, Eriksson, M, Evans, DG, Fasching, PA, Figueroa, J, Fritschi, L, Gabrielson, M, Gago-Dominguez, M, Gao, C, Gapstur, SM, Gaudet, MM, Giles, GG, Gonzalez-Neira, A, Guenel, P, Haeberle, L, Haiman, CA, Hakansson, N, Hall, P, Hamann, U, Hatse, S, Heyworth, J, Holleczek, B, Hoover, RN, Hopper, JL, Howell, A, Hunter, DJ, John, EM, Jones, ME, Kaaks, R, Keeman, R, Kitahara, CM, Ko, Y-D, Koutros, S, Kurian, AW, Lambrechts, D, Le Marchand, L, Lee, E, Lejbkowicz, F, Linet, M, Lissowska, J, Llaneza, A, MacInnis, RJ, Martinez, ME, Maurer, T, McLean, C, Neuhausen, SL, Newman, WG, Norman, A, O'Brien, KM, Olshan, AF, Olson, JE, Olsson, H, Orr, N, Perou, CM, Pita, G, Polley, EC, Prentice, RL, Rennert, G, Rennert, HS, Ruddy, KJ, Sandler, DP, Saunders, C, Schoemaker, MJ, Schoettker, B, Schumacher, F, Scott, C, Scott, RJ, Shu, X-O, Smeets, A, Southey, MC, Spinelli, JJ, Stone, J, Swerdlow, AJ, Tamimi, RM, Taylor, JA, Troester, MA, Vachon, CM, van Veen, EM, Wang, X, Weinberg, CR, Weltens, C, Willett, W, Winham, SJ, Wolk, A, Yang, XR, Zheng, W, Ziogas, A, Dunning, AM, Pharoah, PDP, Schmidt, MK, Kraft, P, Easton, DF, Milne, RL, Garcia-Closas, M, Chang-Claude, J, Kapoor, PM, Mavaddat, N, Choudhury, PP, Wilcox, AN, Lindstrom, S, Behrens, S, Michailidou, K, Dennis, J, Bolla, MK, Wang, Q, Jung, A, Abu-Ful, Z, Ahearn, T, Andrulis, IL, Anton-Culver, H, Arndt, V, Aronson, KJ, Auer, PL, Freeman, LEB, Becher, H, Beckmann, MW, Beeghly-Fadiel, A, Benitez, J, Bernstein, L, Bojesen, SE, Brauch, H, Brenner, H, Bruening, T, Cai, Q, Campa, D, Canzian, F, Carracedo, A, Carter, BD, Castelao, JE, Chanock, SJ, Chatterjee, N, Chenevix-Trench, G, Clarke, CL, Couch, FJ, Cox, A, Cross, SS, Czene, K, Dai, JY, Earp, HS, Ekici, AB, Eliassen, AH, Eriksson, M, Evans, DG, Fasching, PA, Figueroa, J, Fritschi, L, Gabrielson, M, Gago-Dominguez, M, Gao, C, Gapstur, SM, Gaudet, MM, Giles, GG, Gonzalez-Neira, A, Guenel, P, Haeberle, L, Haiman, CA, Hakansson, N, Hall, P, Hamann, U, Hatse, S, Heyworth, J, Holleczek, B, Hoover, RN, Hopper, JL, Howell, A, Hunter, DJ, John, EM, Jones, ME, Kaaks, R, Keeman, R, Kitahara, CM, Ko, Y-D, Koutros, S, Kurian, AW, Lambrechts, D, Le Marchand, L, Lee, E, Lejbkowicz, F, Linet, M, Lissowska, J, Llaneza, A, MacInnis, RJ, Martinez, ME, Maurer, T, McLean, C, Neuhausen, SL, Newman, WG, Norman, A, O'Brien, KM, Olshan, AF, Olson, JE, Olsson, H, Orr, N, Perou, CM, Pita, G, Polley, EC, Prentice, RL, Rennert, G, Rennert, HS, Ruddy, KJ, Sandler, DP, Saunders, C, Schoemaker, MJ, Schoettker, B, Schumacher, F, Scott, C, Scott, RJ, Shu, X-O, Smeets, A, Southey, MC, Spinelli, JJ, Stone, J, Swerdlow, AJ, Tamimi, RM, Taylor, JA, Troester, MA, Vachon, CM, van Veen, EM, Wang, X, Weinberg, CR, Weltens, C, Willett, W, Winham, SJ, Wolk, A, Yang, XR, Zheng, W, Ziogas, A, Dunning, AM, Pharoah, PDP, Schmidt, MK, Kraft, P, Easton, DF, Milne, RL, 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.
Published: 2021

39. Association of germline genetic variants with breast cancer-specific survival in patient subgroups defined by clinic-pathological variables related to tumor biology and type of systemic treatment

Author: Morra, A, Escala-Garcia, M, Beesley, J, Keeman, R, Canisius, S, Ahearn, TU, Andrulis, IL, Anton-Culver, H, Arndt, V, Auer, PL, Augustinsson, A, Freeman, LEB, Becher, H, Beckmann, MW, Behrens, S, Bojesen, SE, Bolla, MK, Brenner, H, Bruening, T, Buys, SS, Caan, B, Campa, D, Canzian, F, Castelao, JE, Chang-Claude, J, Chanock, SJ, Cheng, T-YD, Clarke, CL, Colonna, S, Couch, FJ, Cox, A, Cross, SS, Czene, K, Daly, MB, Dennis, J, Dork, T, Dossus, L, Dunning, AM, Dwek, M, Eccles, DM, Ekici, AB, Eliassen, AH, Eriksson, M, Evans, DG, Fasching, PA, Flyger, H, Fritschi, L, Gago-Dominguez, M, Garcia-Saenz, JA, Giles, GG, Grip, M, Guenel, P, Guendert, M, Hahnen, E, Haiman, CA, Hakansson, N, Hall, P, Hamann, U, Hart, SN, Hartikainen, JM, Hartmann, A, He, W, Hooning, MJ, Hoppe, R, Hopper, JL, Howell, A, Hunter, DJ, Jager, A, Jakubowska, A, Janni, W, John, EM, Jung, AY, Kaaks, R, Keupers, M, Kitahara, CM, Koutros, S, Kraft, P, Kristensen, VN, Kurian, AW, Lacey, J, Lambrechts, D, Le Marchand, L, Lindblom, A, Linet, M, Luben, RN, Lush, M, Mannermaa, A, Manoochehri, M, Margolin, S, Martens, JWM, Martinez, ME, Mavroudis, D, Michailidou, K, Milne, RL, Mulligan, AM, Muranen, TA, Nevanlinna, H, Newman, WG, Nielsen, SF, Nordestgaard, BG, Olshan, AF, Olsson, H, Orr, N, Park-Simon, T-W, Patel, A, Peissel, B, Peterlongo, P, Plaseska-Karanfilska, D, Prajzendanc, K, Prentice, R, Presneau, N, Rack, B, Rennert, G, Rennert, HS, Rhenius, V, Romero, A, Roylance, R, Lubinski, J, Ruebner, M, Saloustros, E, Sawyer, EJ, Schmutzler, RK, Schneeweiss, A, Scott, C, Shah, M, Smichkoska, S, Southey, MC, Stone, J, Surowy, H, Swerdlow, AJ, Tamimi, RM, Tapper, WJ, Teras, LR, Terry, MB, Tollenaar, RAEM, Tomlinson, I, Troester, MA, Truong, T, Vachon, CM, Wang, Q, Hurson, AN, Winqvist, R, Wolk, A, Ziogas, A, Brauch, H, Garcia-Closas, M, Pharoah, PDP, Easton, DF, Chenevix-Trench, G, Schmidt, MK, Morra, A, Escala-Garcia, M, Beesley, J, Keeman, R, Canisius, S, Ahearn, TU, Andrulis, IL, Anton-Culver, H, Arndt, V, Auer, PL, Augustinsson, A, Freeman, LEB, Becher, H, Beckmann, MW, Behrens, S, Bojesen, SE, Bolla, MK, Brenner, H, Bruening, T, Buys, SS, Caan, B, Campa, D, Canzian, F, Castelao, JE, Chang-Claude, J, Chanock, SJ, Cheng, T-YD, Clarke, CL, Colonna, S, Couch, FJ, Cox, A, Cross, SS, Czene, K, Daly, MB, Dennis, J, Dork, T, Dossus, L, Dunning, AM, Dwek, M, Eccles, DM, Ekici, AB, Eliassen, AH, Eriksson, M, Evans, DG, Fasching, PA, Flyger, H, Fritschi, L, Gago-Dominguez, M, Garcia-Saenz, JA, Giles, GG, Grip, M, Guenel, P, Guendert, M, Hahnen, E, Haiman, CA, Hakansson, N, Hall, P, Hamann, U, Hart, SN, Hartikainen, JM, Hartmann, A, He, W, Hooning, MJ, Hoppe, R, Hopper, JL, Howell, A, Hunter, DJ, Jager, A, Jakubowska, A, Janni, W, John, EM, Jung, AY, Kaaks, R, Keupers, M, Kitahara, CM, Koutros, S, Kraft, P, Kristensen, VN, Kurian, AW, Lacey, J, Lambrechts, D, Le Marchand, L, Lindblom, A, Linet, M, Luben, RN, Lush, M, Mannermaa, A, Manoochehri, M, Margolin, S, Martens, JWM, Martinez, ME, Mavroudis, D, Michailidou, K, Milne, RL, Mulligan, AM, Muranen, TA, Nevanlinna, H, Newman, WG, Nielsen, SF, Nordestgaard, BG, Olshan, AF, Olsson, H, Orr, N, Park-Simon, T-W, Patel, A, Peissel, B, Peterlongo, P, Plaseska-Karanfilska, D, Prajzendanc, K, Prentice, R, Presneau, N, Rack, B, Rennert, G, Rennert, HS, Rhenius, V, Romero, A, Roylance, R, Lubinski, J, Ruebner, M, Saloustros, E, Sawyer, EJ, Schmutzler, RK, Schneeweiss, A, Scott, C, Shah, M, Smichkoska, S, Southey, MC, Stone, J, Surowy, H, Swerdlow, AJ, Tamimi, RM, Tapper, WJ, Teras, LR, Terry, MB, Tollenaar, RAEM, Tomlinson, I, Troester, MA, Truong, T, Vachon, CM, Wang, Q, Hurson, AN, Winqvist, R, Wolk, A, Ziogas, A, Brauch, H, Garcia-Closas, M, Pharoah, PDP, Easton, DF, Chenevix-Trench, G, and Schmidt, MK
Abstract: BACKGROUND: Given the high heterogeneity among breast tumors, associations between common germline genetic variants and survival that may exist within specific subgroups could go undetected in an unstratified set of breast cancer patients. METHODS: We performed genome-wide association analyses within 15 subgroups of breast cancer patients based on prognostic factors, including hormone receptors, tumor grade, age, and type of systemic treatment. Analyses were based on 91,686 female patients of European ancestry from the Breast Cancer Association Consortium, including 7531 breast cancer-specific deaths over a median follow-up of 8.1 years. Cox regression was used to assess associations of common germline variants with 15-year and 5-year breast cancer-specific survival. We assessed the probability of these associations being true positives via the Bayesian false discovery probability (BFDP < 0.15). RESULTS: Evidence of associations with breast cancer-specific survival was observed in three patient subgroups, with variant rs5934618 in patients with grade 3 tumors (15-year-hazard ratio (HR) [95% confidence interval (CI)] 1.32 [1.20, 1.45], P = 1.4E-08, BFDP = 0.01, per G allele); variant rs4679741 in patients with ER-positive tumors treated with endocrine therapy (15-year-HR [95% CI] 1.18 [1.11, 1.26], P = 1.6E-07, BFDP = 0.09, per G allele); variants rs1106333 (15-year-HR [95% CI] 1.68 [1.39,2.03], P = 5.6E-08, BFDP = 0.12, per A allele) and rs78754389 (5-year-HR [95% CI] 1.79 [1.46,2.20], P = 1.7E-08, BFDP = 0.07, per A allele), in patients with ER-negative tumors treated with chemotherapy. CONCLUSIONS: We found evidence of four loci associated with breast cancer-specific survival within three patient subgroups. There was limited evidence for the existence of associations in other patient subgroups. However, the power for many subgroups is limited due to the low number of events. Even so, our results suggest that the impact of common germline genetic variants on breast
Published: 2021

40. CYP3A7*1C allele: linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers

Author: Johnson, N, Maguire, S, Morra, A, Kapoor, PM, Tomczyk, K, Jones, ME, Schoemaker, MJ, Gilham, C, Bolla, MK, Wang, Q, Dennis, J, Ahearn, TU, Andrulis, IL, Anton-Culver, H, Antonenkova, NN, Arndt, V, Aronson, KJ, Augustinsson, A, Baynes, C, Freeman, LEB, Beckmann, MW, Benitez, J, Bermisheva, M, Blomqvist, C, Boeckx, B, Bogdanova, NV, Bojesen, SE, Brauch, H, Brenner, H, Burwinkel, B, Campa, D, Canzian, F, Castelao, JE, Chanock, SJ, Chenevix-Trench, G, Clarke, CL, Conroy, DM, Couch, FJ, Cox, A, Cross, SS, Czene, K, Doerk, T, Eliassen, AH, Engel, C, Evans, DG, Fasching, PA, Figueroa, J, Floris, G, Flyger, H, Gago-Dominguez, M, Gapstur, SM, Garcia-Closas, M, Gaudet, MM, Giles, GG, Goldberg, MS, Gonzalez-Neira, A, Guenel, P, Hahnen, E, Haiman, CA, Hakansson, N, Hall, P, Hamann, U, Harrington, PA, Hart, SN, Hooning, MJ, Hopper, JL, Howell, A, Hunter, DJ, Jager, A, Jakubowska, A, John, EM, Kaaks, R, Keeman, R, Khusnutdinova, E, Kitahara, CM, Kosma, V-M, Koutros, S, Kraft, P, Kristensen, VN, Kurian, AW, Lambrechts, D, Le Marchand, L, Linet, M, Lubinski, J, Mannermaa, A, Manoukian, S, Margolin, S, Martens, JWM, Mavroudis, D, Mayes, R, Meindl, A, Milne, RL, Neuhausen, SL, Nevanlinna, H, Newman, WG, Nielsen, SF, Nordestgaard, BG, Obi, N, Olshan, AF, Olson, JE, Olsson, H, Orban, E, Park-Simon, T-W, Peterlongo, P, Plaseska-Karanfilska, D, Pylkas, K, Rennert, G, Rennert, HS, Ruddy, KJ, Saloustros, E, Sandler, DP, Sawyer, EJ, Schmutzler, RK, Scott, C, Shu, X-O, Simard, J, Smichkoska, S, Sohn, C, Southey, MC, Spinelli, JJ, Stone, J, Tamimi, RM, Taylor, JA, Tollenaar, RAEM, Tomlinson, I, Troester, MA, Truong, T, Vachon, CM, van Veen, EM, Wang, SS, Weinberg, CR, Wendt, C, Wildiers, H, Winqvist, R, Wolk, A, Zheng, W, Ziogas, A, Dunning, AM, Pharoah, PDP, Easton, DF, Howie, AF, Peto, J, dos-Santos-Silva, I, Swerdlow, AJ, Chang-Claude, J, Schmidt, MK, Orr, N, Fletcher, O, Johnson, N, Maguire, S, Morra, A, Kapoor, PM, Tomczyk, K, Jones, ME, Schoemaker, MJ, Gilham, C, Bolla, MK, Wang, Q, Dennis, J, Ahearn, TU, Andrulis, IL, Anton-Culver, H, Antonenkova, NN, Arndt, V, Aronson, KJ, Augustinsson, A, Baynes, C, Freeman, LEB, Beckmann, MW, Benitez, J, Bermisheva, M, Blomqvist, C, Boeckx, B, Bogdanova, NV, Bojesen, SE, Brauch, H, Brenner, H, Burwinkel, B, Campa, D, Canzian, F, Castelao, JE, Chanock, SJ, Chenevix-Trench, G, Clarke, CL, Conroy, DM, Couch, FJ, Cox, A, Cross, SS, Czene, K, Doerk, T, Eliassen, AH, Engel, C, Evans, DG, Fasching, PA, Figueroa, J, Floris, G, Flyger, H, Gago-Dominguez, M, Gapstur, SM, Garcia-Closas, M, Gaudet, MM, Giles, GG, Goldberg, MS, Gonzalez-Neira, A, Guenel, P, Hahnen, E, Haiman, CA, Hakansson, N, Hall, P, Hamann, U, Harrington, PA, Hart, SN, Hooning, MJ, Hopper, JL, Howell, A, Hunter, DJ, Jager, A, Jakubowska, A, John, EM, Kaaks, R, Keeman, R, Khusnutdinova, E, Kitahara, CM, Kosma, V-M, Koutros, S, Kraft, P, Kristensen, VN, Kurian, AW, Lambrechts, D, Le Marchand, L, Linet, M, Lubinski, J, Mannermaa, A, Manoukian, S, Margolin, S, Martens, JWM, Mavroudis, D, Mayes, R, Meindl, A, Milne, RL, Neuhausen, SL, Nevanlinna, H, Newman, WG, Nielsen, SF, Nordestgaard, BG, Obi, N, Olshan, AF, Olson, JE, Olsson, H, Orban, E, Park-Simon, T-W, Peterlongo, P, Plaseska-Karanfilska, D, Pylkas, K, Rennert, G, Rennert, HS, Ruddy, KJ, Saloustros, E, Sandler, DP, Sawyer, EJ, Schmutzler, RK, Scott, C, Shu, X-O, Simard, J, Smichkoska, S, Sohn, C, Southey, MC, Spinelli, JJ, Stone, J, Tamimi, RM, Taylor, JA, Tollenaar, RAEM, Tomlinson, I, Troester, MA, Truong, T, Vachon, CM, van Veen, EM, Wang, SS, Weinberg, CR, Wendt, C, Wildiers, H, Winqvist, R, Wolk, A, Zheng, W, Ziogas, A, Dunning, AM, Pharoah, PDP, Easton, DF, Howie, AF, Peto, J, dos-Santos-Silva, I, Swerdlow, AJ, Chang-Claude, J, Schmidt, MK, 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. 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 × 10-8). 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.
Published: 2021

41. A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers (vol 12, 1078, 2021)

Author: Coignard, J, Lush, M, Beesley, J, O'Mara, TA, Dennis, J, Tyrer, JP, Barnes, DR, McGuffog, L, Leslie, G, Bolla, MK, Adank, MA, Agata, S, Ahearn, T, Aittomaki, K, Andrulis, IL, Anton-Culver, H, Arndt, V, Arnold, N, Aronson, KJ, Arun, BK, Augustinsson, A, Azzollini, J, Barrowdale, D, Baynes, C, Becher, H, Bermisheva, M, Bernstein, L, Bialkowska, K, Blomqvist, C, Bojesen, SE, Bonanni, B, Borg, A, Brauch, H, Brenner, H, Burwinkel, B, Buys, SS, Caldes, T, Caligo, MA, Campa, D, Carter, BD, Castelao, JE, Chang-Claude, J, Chanock, SJ, Chung, WK, Claes, KBM, Clarke, CL, Collee, JM, Conroy, DM, Czene, K, Daly, MB, Devilee, P, Diez, O, Ding, YC, Domchek, SM, Doerk, T, dos-Santos-Silva, I, Dunning, AM, Dwek, M, Eccles, DM, Eliassen, AH, Engel, C, Eriksson, M, Evans, DG, Fasching, PA, Flyger, H, Fostira, F, Friedman, E, Fritschi, L, Frost, D, Gago-Dominguez, M, Gapstur, SM, Garber, J, Garcia-Barberan, V, Garcia-Closas, M, Garcia-Saenz, JA, Gaudet, MM, Gayther, SA, Gehrig, A, Georgoulias, V, Giles, GG, Godwin, AK, Goldberg, MS, Goldgar, DE, Gonzalez-Neira, A, Greene, MH, Guenel, P, Haeberle, L, Hahnen, E, Haiman, CA, Hakansson, N, Hall, P, Hamann, U, Harrington, PA, Hart, SN, He, W, Hogervorst, FBL, Hollestelle, A, Hopper, JL, Horcasitas, DJ, Hulick, PJ, Hunter, DJ, Imyanitov, EN, Fox, S, van der Hout, AH, Clarke, C, Jager, A, Jakubowska, A, James, PA, Jensen, UB, John, EM, Jones, ME, Kaaks, R, Kapoor, PM, Karlan, BY, Keeman, R, Khusnutdinova, E, Kiiski, JI, Ko, Y-D, Kosma, V-M, Kraft, P, Kurian, AW, Laitman, Y, Lambrechts, D, Le Marchand, L, Lester, J, Lesueur, F, Lindstrom, T, Lopez-Fernandez, A, Loud, JT, Luccarini, C, Mannermaa, A, Manoukian, S, Margolin, S, Martens, JWM, Mebirouk, N, Meindl, A, Miller, A, Milne, RL, Montagna, M, Nathanson, KL, Neuhausen, SL, Nevanlinna, H, Nielsen, FC, O'Brien, KM, Olopade, OI, Olson, JE, Olsson, H, Osorio, A, Ottini, L, Park-Simon, T-W, Parsons, MT, Pedersen, IS, Peshkin, B, Peterlongo, P, Peto, J, Pharoah, PDP, Phillips, K-A, Polley, EC, Poppe, B, Presneau, N, Pujana, MA, Punie, K, Radice, P, Rantala, J, Rashid, MU, Rennert, G, Rennert, HS, Robson, M, Romero, A, Rossing, M, Saloustros, E, Sandler, DP, Santella, R, Scheuner, MT, Schmidt, MK, Schmidt, G, Scott, C, Sharma, P, Soucy, P, Southey, MC, Spinelli, JJ, Steinsnyder, Z, Stone, J, Stoppa-Lyonnet, D, Swerdlow, A, Tamimi, RM, Tapper, WJ, Taylor, JA, Terry, MB, Teule, A, Thull, DL, Tischkowitz, M, Toland, AE, Torres, D, Trainer, AH, Truong, T, Tung, N, Vachon, CM, Vega, A, Vijai, J, Wang, Q, Wappenschmidt, B, Weinberg, CR, Weitzel, JN, Wendt, C, Wolk, A, Yadav, S, Yang, XR, Yannoukakos, D, Zheng, W, Ziogas, A, Zorn, KK, Park, SK, Thomassen, M, Offit, K, Schmutzler, RK, Couch, FJ, Simard, J, Chenevix-Trench, G, Easton, DF, Andrieu, N, Antoniou, AC, Coignard, J, Lush, M, Beesley, J, O'Mara, TA, Dennis, J, Tyrer, JP, Barnes, DR, McGuffog, L, Leslie, G, Bolla, MK, Adank, MA, Agata, S, Ahearn, T, Aittomaki, K, Andrulis, IL, Anton-Culver, H, Arndt, V, Arnold, N, Aronson, KJ, Arun, BK, Augustinsson, A, Azzollini, J, Barrowdale, D, Baynes, C, Becher, H, Bermisheva, M, Bernstein, L, Bialkowska, K, Blomqvist, C, Bojesen, SE, Bonanni, B, Borg, A, Brauch, H, Brenner, H, Burwinkel, B, Buys, SS, Caldes, T, Caligo, MA, Campa, D, Carter, BD, Castelao, JE, Chang-Claude, J, Chanock, SJ, Chung, WK, Claes, KBM, Clarke, CL, Collee, JM, Conroy, DM, Czene, K, Daly, MB, Devilee, P, Diez, O, Ding, YC, Domchek, SM, Doerk, T, dos-Santos-Silva, I, Dunning, AM, Dwek, M, Eccles, DM, Eliassen, AH, Engel, C, Eriksson, M, Evans, DG, Fasching, PA, Flyger, H, Fostira, F, Friedman, E, Fritschi, L, Frost, D, Gago-Dominguez, M, Gapstur, SM, Garber, J, Garcia-Barberan, V, Garcia-Closas, M, Garcia-Saenz, JA, Gaudet, MM, Gayther, SA, Gehrig, A, Georgoulias, V, Giles, GG, Godwin, AK, Goldberg, MS, Goldgar, DE, Gonzalez-Neira, A, Greene, MH, Guenel, P, Haeberle, L, Hahnen, E, Haiman, CA, Hakansson, N, Hall, P, Hamann, U, Harrington, PA, Hart, SN, He, W, Hogervorst, FBL, Hollestelle, A, Hopper, JL, Horcasitas, DJ, Hulick, PJ, Hunter, DJ, Imyanitov, EN, Fox, S, van der Hout, AH, Clarke, C, Jager, A, Jakubowska, A, James, PA, Jensen, UB, John, EM, Jones, ME, Kaaks, R, Kapoor, PM, Karlan, BY, Keeman, R, Khusnutdinova, E, Kiiski, JI, Ko, Y-D, Kosma, V-M, Kraft, P, Kurian, AW, Laitman, Y, Lambrechts, D, Le Marchand, L, Lester, J, Lesueur, F, Lindstrom, T, Lopez-Fernandez, A, Loud, JT, Luccarini, C, Mannermaa, A, Manoukian, S, Margolin, S, Martens, JWM, Mebirouk, N, Meindl, A, Miller, A, Milne, RL, Montagna, M, Nathanson, KL, Neuhausen, SL, Nevanlinna, H, Nielsen, FC, O'Brien, KM, Olopade, OI, Olson, JE, Olsson, H, Osorio, A, Ottini, L, Park-Simon, T-W, Parsons, MT, Pedersen, IS, Peshkin, B, Peterlongo, P, Peto, J, Pharoah, PDP, Phillips, K-A, Polley, EC, Poppe, B, Presneau, N, Pujana, MA, Punie, K, Radice, P, Rantala, J, Rashid, MU, Rennert, G, Rennert, HS, Robson, M, Romero, A, Rossing, M, Saloustros, E, Sandler, DP, Santella, R, Scheuner, MT, Schmidt, MK, Schmidt, G, Scott, C, Sharma, P, Soucy, P, Southey, MC, Spinelli, JJ, Steinsnyder, Z, Stone, J, Stoppa-Lyonnet, D, Swerdlow, A, Tamimi, RM, Tapper, WJ, Taylor, JA, Terry, MB, Teule, A, Thull, DL, Tischkowitz, M, Toland, AE, Torres, D, Trainer, AH, Truong, T, Tung, N, Vachon, CM, Vega, A, Vijai, J, Wang, Q, Wappenschmidt, B, Weinberg, CR, Weitzel, JN, Wendt, C, Wolk, A, Yadav, S, Yang, XR, Yannoukakos, D, Zheng, W, Ziogas, A, Zorn, KK, Park, SK, Thomassen, M, Offit, K, Schmutzler, RK, Couch, FJ, Simard, J, Chenevix-Trench, G, Easton, DF, Andrieu, N, and Antoniou, AC
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

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

Author: Coignard, J, Lush, M, Beesley, J, O'Mara, TA, Dennis, J, Tyrer, JP, Barnes, DR, McGuffog, L, Leslie, G, Bolla, MK, Adank, MA, Agata, S, Ahearn, T, Aittomäki, K, Andrulis, IL, Anton-Culver, H, Arndt, V, Arnold, N, Aronson, KJ, Arun, BK, Augustinsson, A, Azzollini, J, Barrowdale, D, Baynes, C, Becher, H, Bermisheva, M, Bernstein, L, Białkowska, K, Blomqvist, C, Bojesen, SE, Bonanni, B, Borg, A, Brauch, H, Brenner, H, Burwinkel, B, Buys, SS, Caldés, T, Caligo, MA, Campa, D, Carter, BD, Castelao, JE, Chang-Claude, J, Chanock, SJ, Chung, WK, Claes, KBM, Clarke, CL, GEMO Study Collaborators, EMBRACE Collaborators, Collée, JM, Conroy, DM, Czene, K, Daly, MB, Devilee, P, Diez, O, Ding, YC, Domchek, SM, Dörk, T, Dos-Santos-Silva, I, Dunning, AM, Dwek, M, Eccles, DM, Eliassen, AH, Engel, C, Eriksson, M, Evans, DG, Fasching, PA, Flyger, H, Fostira, F, Friedman, E, Fritschi, L, Frost, D, Gago-Dominguez, M, Gapstur, SM, Garber, J, Garcia-Barberan, V, García-Closas, M, García-Sáenz, JA, Gaudet, MM, Gayther, SA, Gehrig, A, Georgoulias, V, Giles, GG, Godwin, AK, Goldberg, MS, Goldgar, DE, González-Neira, A, Greene, MH, Guénel, P, Haeberle, L, Hahnen, E, Haiman, CA, Håkansson, N, Hall, P, Hamann, U, Harrington, PA, Hart, SN, He, W, Hogervorst, FBL, Hollestelle, A, Hopper, JL, Horcasitas, DJ, Hulick, PJ, Hunter, DJ, Imyanitov, EN, KConFab Investigators, HEBON Investigators, ABCTB Investigators, Jager, A, Jakubowska, A, James, PA, Jensen, UB, John, EM, Jones, ME, Kaaks, R, Kapoor, PM, Karlan, BY, Keeman, R, Khusnutdinova, E, Kiiski, JI, Ko, Y-D, Kosma, V-M, Kraft, P, Kurian, AW, Laitman, Y, Lambrechts, D, Le Marchand, L, Lester, J, Lesueur, F, Lindstrom, T, Lopez-Fernández, A, Loud, JT, Luccarini, C, Mannermaa, A, Manoukian, S, Margolin, S, Martens, JWM, Mebirouk, N, Meindl, A, Miller, A, Milne, RL, Montagna, M, Nathanson, KL, Neuhausen, SL, Nevanlinna, H, Nielsen, FC, O'Brien, KM, Olopade, OI, Olson, JE, Olsson, H, Osorio, A, Ottini, L, Park-Simon, T-W, Parsons, MT, Pedersen, IS, Peshkin, B, Peterlongo, P, Peto, J, Pharoah, PDP, Phillips, K-A, Polley, EC, Poppe, B, Presneau, N, Pujana, MA, Punie, K, Radice, P, Rantala, J, Rashid, MU, Rennert, G, Rennert, HS, Robson, M, Romero, A, Rossing, M, Saloustros, E, Sandler, DP, Santella, R, Scheuner, MT, Schmidt, MK, Schmidt, G, Scott, C, Sharma, P, Soucy, P, Southey, MC, Spinelli, JJ, Steinsnyder, Z, Stone, J, Stoppa-Lyonnet, D, Swerdlow, A, Tamimi, RM, Tapper, WJ, Taylor, JA, Terry, MB, Teulé, A, Thull, DL, Tischkowitz, M, Toland, AE, Torres, D, Trainer, AH, Truong, T, Tung, N, Vachon, CM, Vega, A, Vijai, J, Wang, Q, Wappenschmidt, B, Weinberg, CR, Weitzel, JN, Wendt, C, Wolk, A, Yadav, S, Yang, XR, Yannoukakos, D, Zheng, W, Ziogas, A, Zorn, KK, Park, SK, Thomassen, M, Offit, K, Schmutzler, RK, Couch, FJ, Simard, J, Chenevix-Trench, G, Easton, DF, Andrieu, N, Antoniou, AC, Coignard, J, Lush, M, Beesley, J, O'Mara, TA, Dennis, J, Tyrer, JP, Barnes, DR, McGuffog, L, Leslie, G, Bolla, MK, Adank, MA, Agata, S, Ahearn, T, Aittomäki, K, Andrulis, IL, Anton-Culver, H, Arndt, V, Arnold, N, Aronson, KJ, Arun, BK, Augustinsson, A, Azzollini, J, Barrowdale, D, Baynes, C, Becher, H, Bermisheva, M, Bernstein, L, Białkowska, K, Blomqvist, C, Bojesen, SE, Bonanni, B, Borg, A, Brauch, H, Brenner, H, Burwinkel, B, Buys, SS, Caldés, T, Caligo, MA, Campa, D, Carter, BD, Castelao, JE, Chang-Claude, J, Chanock, SJ, Chung, WK, Claes, KBM, Clarke, CL, GEMO Study Collaborators, EMBRACE Collaborators, Collée, JM, Conroy, DM, Czene, K, Daly, MB, Devilee, P, Diez, O, Ding, YC, Domchek, SM, Dörk, T, Dos-Santos-Silva, I, Dunning, AM, Dwek, M, Eccles, DM, Eliassen, AH, Engel, C, Eriksson, M, Evans, DG, Fasching, PA, Flyger, H, Fostira, F, Friedman, E, Fritschi, L, Frost, D, Gago-Dominguez, M, Gapstur, SM, Garber, J, Garcia-Barberan, V, García-Closas, M, García-Sáenz, JA, Gaudet, MM, Gayther, SA, Gehrig, A, Georgoulias, V, Giles, GG, Godwin, AK, Goldberg, MS, Goldgar, DE, González-Neira, A, Greene, MH, Guénel, P, Haeberle, L, Hahnen, E, Haiman, CA, Håkansson, N, Hall, P, Hamann, U, Harrington, PA, Hart, SN, He, W, Hogervorst, FBL, Hollestelle, A, Hopper, JL, Horcasitas, DJ, Hulick, PJ, Hunter, DJ, Imyanitov, EN, KConFab Investigators, HEBON Investigators, ABCTB Investigators, Jager, A, Jakubowska, A, James, PA, Jensen, UB, John, EM, Jones, ME, Kaaks, R, Kapoor, PM, Karlan, BY, Keeman, R, Khusnutdinova, E, Kiiski, JI, Ko, Y-D, Kosma, V-M, Kraft, P, Kurian, AW, Laitman, Y, Lambrechts, D, Le Marchand, L, Lester, J, Lesueur, F, Lindstrom, T, Lopez-Fernández, A, Loud, JT, Luccarini, C, Mannermaa, A, Manoukian, S, Margolin, S, Martens, JWM, Mebirouk, N, Meindl, A, Miller, A, Milne, RL, Montagna, M, Nathanson, KL, Neuhausen, SL, Nevanlinna, H, Nielsen, FC, O'Brien, KM, Olopade, OI, Olson, JE, Olsson, H, Osorio, A, Ottini, L, Park-Simon, T-W, Parsons, MT, Pedersen, IS, Peshkin, B, Peterlongo, P, Peto, J, Pharoah, PDP, Phillips, K-A, Polley, EC, Poppe, B, Presneau, N, Pujana, MA, Punie, K, Radice, P, Rantala, J, Rashid, MU, Rennert, G, Rennert, HS, Robson, M, Romero, A, Rossing, M, Saloustros, E, Sandler, DP, Santella, R, Scheuner, MT, Schmidt, MK, Schmidt, G, Scott, C, Sharma, P, Soucy, P, Southey, MC, Spinelli, JJ, Steinsnyder, Z, Stone, J, Stoppa-Lyonnet, D, Swerdlow, A, Tamimi, RM, Tapper, WJ, Taylor, JA, Terry, MB, Teulé, A, Thull, DL, Tischkowitz, M, Toland, AE, Torres, D, Trainer, AH, Truong, T, Tung, N, Vachon, CM, Vega, A, Vijai, J, Wang, Q, Wappenschmidt, B, Weinberg, CR, Weitzel, JN, Wendt, C, Wolk, A, Yadav, S, Yang, XR, Yannoukakos, D, Zheng, W, Ziogas, A, Zorn, KK, Park, SK, Thomassen, M, Offit, K, Schmutzler, RK, Couch, FJ, Simard, J, Chenevix-Trench, G, Easton, DF, Andrieu, N, and Antoniou, AC
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

43. Mendelian randomisation study of smoking exposure in relation to breast cancer risk

Author: Park, H. A. (Hanla A.), Neumeyer, S. (Sonja), Michailidou, K. (Kyriaki), 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), Baten, A. (Adinda), Freeman, L. E. (Laura E. Beane), Becher, H. (Heiko), Beckmann, M. W. (Matthias W.), Behrens, S. (Sabine), Benitez, J. (Javier), Bermisheva, M. (Marina), Bogdanova, N. V. (Natalia, V), Bojesen, S. E. (Stig E.), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Brucker, S. Y. (Sara Y.), 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), Daly, M. B. (Mary B.), Devilee, P. (Peter), Dork, T. (Thilo), Dos-Santos-Silva, I. (Isabel), 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 A.), Flyger, H. (Henrik), Fritschi, L. (Lin), Garcia-Closas, M. (Montserrat), Garcia-Saenz, J. A. (Jose A.), Gaudet, M. M. (Mia M.), Giles, G. G. (Graham G.), Glendon, G. (Gord), Goldberg, M. S. (Mark S.), Goldgar, D. E. (David E.), Gonzalez-Neira, A. (Anna), Grip, M. (Mervi), Guenel, P. (Pascal), Hahnen, E. (Eric), Haiman, C. A. (Christopher A.), Hakansson, N. (Niclas), Hall, P. (Per), Hamann, U. (Ute), Han, S. (Sileny), Harkness, E. F. (Elaine F.), Hart, S. N. (Steven N.), He, W. (Wei), Heemskerk-Gerritsen, B. A. (Bernadette A. M.), Hopper, J. L. (John L.), Hunter, D. J. (David J.), Jager, A. (Agnes), Jakubowska, A. (Anna), John, E. M. (Esther M.), Jung, A. (Audrey), Kaaks, R. (Rudolf), Kapoor, P. M. (Pooja Middha), Keeman, R. (Renske), Khusnutdinova, E. (Elza), Kitahara, C. M. (Cari M.), Koppert, L. B. (Linetta B.), Koutros, S. (Stella), Kristensen, V. N. (Vessela N.), Kurian, A. W. (Allison W.), Lacey, J. (James), Lambrechts, D. (Diether), LeMarchand, L. (Loic), Lo, W.-Y. (Wing-Yee), Mannermaa, A. (Arto), Manoochehri, M. (Mehdi), Margolin, S. (Sara), ElenaMartinez, M. (Maria), Mavroudis, D. (Dimitrios), Meindl, A. (Alfons), Menon, U. (Usha), Milne, R. L. (Roger L.), Muranen, T. A. (Taru A.), Nevanlinna, H. (Heli), Newman, W. G. (William G.), Nordestgaard, B. G. (Borge G.), Offit, K. (Kenneth), Olshan, A. F. (Andrew F.), Olsson, H. (Hakan), Park-Simon, T.-W. (Tjoung-Won), Peterlongo, P. (Paolo), Peto, J. (Julian), Plaseska-Karanfilska, D. (Dijana), Presneau, N. (Nadege), Radice, P. (Paolo), Rennert, G. (Gad), Rennert, H. S. (Hedy S.), Romero, A. (Atocha), Saloustros, E. (Emmanouil), Sawyer, E. J. (Elinor J.), Schmidt, M. K. (Marjanka K.), Schmutzler, R. K. (Rita K.), Schoemaker, M. J. (Minouk J.), Schwentner, L. (Lukas), Scott, C. (Christopher), Shah, M. (Mitul), Shu, X.-O. (Xiao-Ou), Simard, J. (Jacques), Smeets, A. (Ann), Southey, M. C. (Melissa C.), Spinelli, J. J. (John J.), Stevens, V. (Victoria), Swerdlow, A. J. (Anthony J.), Tamimi, R. M. (Rulla M.), Tapper, W. J. (William J.), Taylor, J. A. (Jack A.), Terry, M. B. (Mary Beth), Tomlinson, I. (Ian), Troester, M. A. (Melissa A.), Truong, T. (Therese), Vachon, C. M. (Celine M.), van Veen, E. M. (Elke M.), Vijai, J. (Joseph), Wang, S. (Sophia), Wendt, C. (Camilla), Winqvist, R. (Robert), Wolk, A. (Alicja), Ziogas, A. (Argyrios), Dunning, A. M. (Alison M.), Pharoah, P. D. (Paul D. P.), Easton, D. F. (Douglas F.), Zheng, W. (Wei), Kraft, P. (Peter), Chang-Claude, J. (Jenny), Park, H. A. (Hanla A.), Neumeyer, S. (Sonja), Michailidou, K. (Kyriaki), 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), Baten, A. (Adinda), Freeman, L. E. (Laura E. Beane), Becher, H. (Heiko), Beckmann, M. W. (Matthias W.), Behrens, S. (Sabine), Benitez, J. (Javier), Bermisheva, M. (Marina), Bogdanova, N. V. (Natalia, V), Bojesen, S. E. (Stig E.), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Brucker, S. Y. (Sara Y.), 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), Daly, M. B. (Mary B.), Devilee, P. (Peter), Dork, T. (Thilo), Dos-Santos-Silva, I. (Isabel), 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 A.), Flyger, H. (Henrik), Fritschi, L. (Lin), Garcia-Closas, M. (Montserrat), Garcia-Saenz, J. A. (Jose A.), Gaudet, M. M. (Mia M.), Giles, G. G. (Graham G.), Glendon, G. (Gord), Goldberg, M. S. (Mark S.), Goldgar, D. E. (David E.), Gonzalez-Neira, A. (Anna), Grip, M. (Mervi), Guenel, P. (Pascal), Hahnen, E. (Eric), Haiman, C. A. (Christopher A.), Hakansson, N. (Niclas), Hall, P. (Per), Hamann, U. (Ute), Han, S. (Sileny), Harkness, E. F. (Elaine F.), Hart, S. N. (Steven N.), He, W. (Wei), Heemskerk-Gerritsen, B. A. (Bernadette A. M.), Hopper, J. L. (John L.), Hunter, D. J. (David J.), Jager, A. (Agnes), Jakubowska, A. (Anna), John, E. M. (Esther M.), Jung, A. (Audrey), Kaaks, R. (Rudolf), Kapoor, P. M. (Pooja Middha), Keeman, R. (Renske), Khusnutdinova, E. (Elza), Kitahara, C. M. (Cari M.), Koppert, L. B. (Linetta B.), Koutros, S. (Stella), Kristensen, V. N. (Vessela N.), Kurian, A. W. (Allison W.), Lacey, J. (James), Lambrechts, D. (Diether), LeMarchand, L. (Loic), Lo, W.-Y. (Wing-Yee), Mannermaa, A. (Arto), Manoochehri, M. (Mehdi), Margolin, S. (Sara), ElenaMartinez, M. (Maria), Mavroudis, D. (Dimitrios), Meindl, A. (Alfons), Menon, U. (Usha), Milne, R. L. (Roger L.), Muranen, T. A. (Taru A.), Nevanlinna, H. (Heli), Newman, W. G. (William G.), Nordestgaard, B. G. (Borge G.), Offit, K. (Kenneth), Olshan, A. F. (Andrew F.), Olsson, H. (Hakan), Park-Simon, T.-W. (Tjoung-Won), Peterlongo, P. (Paolo), Peto, J. (Julian), Plaseska-Karanfilska, D. (Dijana), Presneau, N. (Nadege), Radice, P. (Paolo), Rennert, G. (Gad), Rennert, H. S. (Hedy S.), Romero, A. (Atocha), Saloustros, E. (Emmanouil), Sawyer, E. J. (Elinor J.), Schmidt, M. K. (Marjanka K.), Schmutzler, R. K. (Rita K.), Schoemaker, M. J. (Minouk J.), Schwentner, L. (Lukas), Scott, C. (Christopher), Shah, M. (Mitul), Shu, X.-O. (Xiao-Ou), Simard, J. (Jacques), Smeets, A. (Ann), Southey, M. C. (Melissa C.), Spinelli, J. J. (John J.), Stevens, V. (Victoria), Swerdlow, A. J. (Anthony J.), Tamimi, R. M. (Rulla M.), Tapper, W. J. (William J.), Taylor, J. A. (Jack A.), Terry, M. B. (Mary Beth), Tomlinson, I. (Ian), Troester, M. A. (Melissa A.), Truong, T. (Therese), Vachon, C. M. (Celine M.), van Veen, E. M. (Elke M.), Vijai, J. (Joseph), Wang, S. (Sophia), Wendt, C. (Camilla), Winqvist, R. (Robert), Wolk, A. (Alicja), Ziogas, A. (Argyrios), Dunning, A. M. (Alison M.), Pharoah, P. D. (Paul D. P.), Easton, D. F. (Douglas F.), Zheng, W. (Wei), Kraft, P. (Peter), and Chang-Claude, J. (Jenny)
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. Conclusions: 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.
Published: 2021

44. Association of germline genetic variants with breast cancer-specific survival in patient subgroups defined by clinic-pathological variables related to tumor biology and type of systemic treatment

Author: Morra, A. (Anna), Escala-Garcia, M. (Maria), Beesley, J. (Jonathan), Keeman, R. (Renske), Canisius, S. (Sander), Ahearn, T. U. (Thomas U.), Andrulis, I. L. (Irene L.), Anton-Culver, H. (Hoda), Arndt, V. (Volker), Auer, P. L. (Paul L.), Augustinsson, A. (Annelie), Freeman, L. E. (Laura E. Beane), Becher, H. (Heiko), Beckmann, M. W. (Matthias W.), Behrens, S. (Sabine), Bojesen, S. E. (Stig E.), Bolla, M. K. (Manjeet K.), Brenner, H. (Hermann), Bruening, T. (Thomas), Buys, S. S. (Saundra S.), Caan, B. (Bette), Campa, D. (Daniele), Canzian, F. (Federico), Castelao, J. E. (Jose E.), Chang-Claude, J. (Jenny), Chanock, S. J. (Stephen J.), Cheng, T. D. (Ting-Yuan David), Clarke, C. L. (Christine L.), Colonna, S. V. (Sarah, V), Couch, F. J. (Fergus J.), Cox, A. (Angela), Cross, S. S. (Simon S.), Czene, K. (Kamila), Daly, M. B. (Mary B.), Dennis, J. (Joe), Dork, T. (Thilo), Dossus, L. (Laure), Dunning, A. M. (Alison M.), Dwek, M. (Miriam), Eccles, D. M. (Diana M.), Ekici, A. B. (Arif B.), Eliassen, A. H. (A. Heather), Eriksson, M. (Mikael), Evans, D. G. (D. Gareth), Fasching, P. A. (Peter A.), Flyger, H. (Henrik), Fritschi, L. (Lin), Gago-Dominguez, M. (Manuela), Garcia-Saenz, J. A. (Jose A.), Giles, G. G. (Graham G.), Grip, M. (Mervi), Guenel, P. (Pascal), Guendert, M. (Melanie), Hahnen, E. (Eric), Haiman, C. A. (Christopher A.), Hakansson, N. (Niclas), Hall, P. (Per), Hamann, U. (Ute), Hart, S. N. (Steven N.), Hartikainen, J. M. (Jaana M.), Hartmann, A. (Arndt), He, W. (Wei), Hooning, M. J. (Maartje J.), Hoppe, R. (Reiner), Hopper, J. L. (John L.), Howell, A. (Anthony), Hunter, D. J. (David J.), Jager, A. (Agnes), Jakubowska, A. (Anna), Janni, W. (Wolfgang), John, E. M. (Esther M.), Jung, A. Y. (Audrey Y.), Kaaks, R. (Rudolf), Keupers, M. (Machteld), Kitahara, C. M. (Cari M.), Koutros, S. (Stella), Kraft, P. (Peter), Kristensen, V. N. (Vessela N.), Kurian, A. W. (Allison W.), Lacey, J. V. (James, V), Lambrechts, D. (Diether), Le Marchand, L. (Loic), Lindblom, A. (Annika), Linet, M. (Martha), Luben, R. N. (Robert N.), Lush, M. (Michael), Mannermaa, A. (Arto), Manoochehri, M. (Mehdi), Margolin, S. (Sara), Martens, J. W. (John W. M.), Martinez, M. E. (Maria Elena), Mavroudis, D. (Dimitrios), Michailidou, K. (Kyriaki), Milne, R. L. (Roger L.), Mulligan, A. M. (Anna Marie), Muranen, T. A. (Taru A.), Nevanlinna, H. (Heli), Newman, W. G. (William G.), Nielsen, S. F. (Sune F.), Nordestgaard, B. G. (Borge G.), Olshan, A. F. (Andrew F.), Olsson, H. (Hakan), Orr, N. (Nick), Park-Simon, T.-W. (Tjoung-Won), Patel, A. V. (Alpa, V), Peissel, B. (Bernard), Peterlongo, P. (Paolo), Plaseska-Karanfilska, D. (Dijana), Prajzendanc, K. (Karolina), Prentice, R. (Ross), Presneau, N. (Nadege), Rack, B. (Brigitte), Rennert, G. (Gad), Rennert, H. S. (Hedy S.), Rhenius, V. (Valerie), Romero, A. (Atocha), Roylance, R. (Rebecca), Lubinski, J. (Jan), Ruebner, M. (Matthias), Saloustros, E. (Emmanouil), Sawyer, E. J. (Elinor J.), Schmutzler, R. K. (Rita K.), Schneeweiss, A. (Andreas), Scott, C. (Christopher), Shah, M. (Mitul), Smichkoska, S. (Snezhana), Southey, M. C. (Melissa C.), Stone, J. (Jennifer), Surowy, H. (Harald), Swerdlow, A. J. (Anthony J.), Tamimi, R. M. (Rulla M.), Tapper, W. J. (William J.), Teras, L. R. (Lauren R.), Terry, M. B. (Mary Beth), Tollenaar, R. A. (Rob A. E. M.), Tomlinson, I. (Ian), Troester, M. A. (Melissa A.), Truong, T. (Therese), Vachon, C. M. (Celine M.), Wang, Q. (Qin), Hurson, A. N. (Amber N.), Winqvist, R. (Robert), Wolk, A. (Alicja), Ziogas, A. (Argyrios), Brauch, H. (Hiltrud), Garcia-Closas, M. (Montserrat), Pharoah, P. D. (Paul D. P.), Easton, D. F. (Douglas F.), Chenevix-Trench, G. (Georgia), Schmidt, M. K. (Marjanka K.), Morra, A. (Anna), Escala-Garcia, M. (Maria), Beesley, J. (Jonathan), Keeman, R. (Renske), Canisius, S. (Sander), Ahearn, T. U. (Thomas U.), Andrulis, I. L. (Irene L.), Anton-Culver, H. (Hoda), Arndt, V. (Volker), Auer, P. L. (Paul L.), Augustinsson, A. (Annelie), Freeman, L. E. (Laura E. Beane), Becher, H. (Heiko), Beckmann, M. W. (Matthias W.), Behrens, S. (Sabine), Bojesen, S. E. (Stig E.), Bolla, M. K. (Manjeet K.), Brenner, H. (Hermann), Bruening, T. (Thomas), Buys, S. S. (Saundra S.), Caan, B. (Bette), Campa, D. (Daniele), Canzian, F. (Federico), Castelao, J. E. (Jose E.), Chang-Claude, J. (Jenny), Chanock, S. J. (Stephen J.), Cheng, T. D. (Ting-Yuan David), Clarke, C. L. (Christine L.), Colonna, S. V. (Sarah, V), Couch, F. J. (Fergus J.), Cox, A. (Angela), Cross, S. S. (Simon S.), Czene, K. (Kamila), Daly, M. B. (Mary B.), Dennis, J. (Joe), Dork, T. (Thilo), Dossus, L. (Laure), Dunning, A. M. (Alison M.), Dwek, M. (Miriam), Eccles, D. M. (Diana M.), Ekici, A. B. (Arif B.), Eliassen, A. H. (A. Heather), Eriksson, M. (Mikael), Evans, D. G. (D. Gareth), Fasching, P. A. (Peter A.), Flyger, H. (Henrik), Fritschi, L. (Lin), Gago-Dominguez, M. (Manuela), Garcia-Saenz, J. A. (Jose A.), Giles, G. G. (Graham G.), Grip, M. (Mervi), Guenel, P. (Pascal), Guendert, M. (Melanie), Hahnen, E. (Eric), Haiman, C. A. (Christopher A.), Hakansson, N. (Niclas), Hall, P. (Per), Hamann, U. (Ute), Hart, S. N. (Steven N.), Hartikainen, J. M. (Jaana M.), Hartmann, A. (Arndt), He, W. (Wei), Hooning, M. J. (Maartje J.), Hoppe, R. (Reiner), Hopper, J. L. (John L.), Howell, A. (Anthony), Hunter, D. J. (David J.), Jager, A. (Agnes), Jakubowska, A. (Anna), Janni, W. (Wolfgang), John, E. M. (Esther M.), Jung, A. Y. (Audrey Y.), Kaaks, R. (Rudolf), Keupers, M. (Machteld), Kitahara, C. M. (Cari M.), Koutros, S. (Stella), Kraft, P. (Peter), Kristensen, V. N. (Vessela N.), Kurian, A. W. (Allison W.), Lacey, J. V. (James, V), Lambrechts, D. (Diether), Le Marchand, L. (Loic), Lindblom, A. (Annika), Linet, M. (Martha), Luben, R. N. (Robert N.), Lush, M. (Michael), Mannermaa, A. (Arto), Manoochehri, M. (Mehdi), Margolin, S. (Sara), Martens, J. W. (John W. M.), Martinez, M. E. (Maria Elena), Mavroudis, D. (Dimitrios), Michailidou, K. (Kyriaki), Milne, R. L. (Roger L.), Mulligan, A. M. (Anna Marie), Muranen, T. A. (Taru A.), Nevanlinna, H. (Heli), Newman, W. G. (William G.), Nielsen, S. F. (Sune F.), Nordestgaard, B. G. (Borge G.), Olshan, A. F. (Andrew F.), Olsson, H. (Hakan), Orr, N. (Nick), Park-Simon, T.-W. (Tjoung-Won), Patel, A. V. (Alpa, V), Peissel, B. (Bernard), Peterlongo, P. (Paolo), Plaseska-Karanfilska, D. (Dijana), Prajzendanc, K. (Karolina), Prentice, R. (Ross), Presneau, N. (Nadege), Rack, B. (Brigitte), Rennert, G. (Gad), Rennert, H. S. (Hedy S.), Rhenius, V. (Valerie), Romero, A. (Atocha), Roylance, R. (Rebecca), Lubinski, J. (Jan), Ruebner, M. (Matthias), Saloustros, E. (Emmanouil), Sawyer, E. J. (Elinor J.), Schmutzler, R. K. (Rita K.), Schneeweiss, A. (Andreas), Scott, C. (Christopher), Shah, M. (Mitul), Smichkoska, S. (Snezhana), Southey, M. C. (Melissa C.), Stone, J. (Jennifer), Surowy, H. (Harald), Swerdlow, A. J. (Anthony J.), Tamimi, R. M. (Rulla M.), Tapper, W. J. (William J.), Teras, L. R. (Lauren R.), Terry, M. B. (Mary Beth), Tollenaar, R. A. (Rob A. E. M.), Tomlinson, I. (Ian), Troester, M. A. (Melissa A.), Truong, T. (Therese), Vachon, C. M. (Celine M.), Wang, Q. (Qin), Hurson, A. N. (Amber N.), Winqvist, R. (Robert), Wolk, A. (Alicja), Ziogas, A. (Argyrios), Brauch, H. (Hiltrud), Garcia-Closas, M. (Montserrat), Pharoah, P. D. (Paul D. P.), Easton, D. F. (Douglas F.), Chenevix-Trench, G. (Georgia), and Schmidt, M. K. (Marjanka K.)
Abstract: Background: Given the high heterogeneity among breast tumors, associations between common germline genetic variants and survival that may exist within specific subgroups could go undetected in an unstratified set of breast cancer patients. Methods: We performed genome-wide association analyses within 15 subgroups of breast cancer patients based on prognostic factors, including hormone receptors, tumor grade, age, and type of systemic treatment. Analyses were based on 91,686 female patients of European ancestry from the Breast Cancer Association Consortium, including 7531 breast cancer-specific deaths over a median follow-up of 8.1 years. Cox regression was used to assess associations of common germline variants with 15-year and 5-year breast cancer-specific survival. We assessed the probability of these associations being true positives via the Bayesian false discovery probability (BFDP & 0.15). Results: Evidence of associations with breast cancer-specific survival was observed in three patient subgroups, with variant rs5934618 in patients with grade 3 tumors (15-year-hazard ratio (HR) [95% confidence interval (CI)] 1.32 [1.20, 1.45], P = 1.4E−08, BFDP = 0.01, per G allele); variant rs4679741 in patients with ER-positive tumors treated with endocrine therapy (15-year-HR [95% CI] 1.18 [1.11, 1.26], P = 1.6E−07, BFDP = 0.09, per G allele); variants rs1106333 (15-year-HR [95% CI] 1.68 [1.39,2.03], P = 5.6E−08, BFDP = 0.12, per A allele) and rs78754389 (5-year-HR [95% CI] 1.79 [1.46,2.20], P = 1.7E−08, BFDP = 0.07, per A allele), in patients with ER-negative tumors treated with chemotherapy. Conclusions: We found evidence of four loci associated with breast cancer-specific survival within three patient subgroups. There was limited evidence for the existence of associations in other patient subgroups. However, the power for many subgroups is limited due to the low number of events. Even so, our results suggest that the impact of common germline genetic varia
Published: 2021

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

Author: Coignard, J, Lush, M, Beesley, J, O'Mara, TA, Dennis, J, Tyrer, JP, Barnes, DR, McGuffog, L, Leslie, G, Bolla, MK, Adank, MA, Agata, S, Ahearn, T, Aittomäki, K, Andrulis, IL, Anton-Culver, H, Arndt, V, Arnold, N, Aronson, KJ, Arun, BK, Augustinsson, A, Azzollini, J, Barrowdale, D, Baynes, C, Becher, H, Bermisheva, M, Bernstein, L, Białkowska, K, Blomqvist, C, Bojesen, SE, Bonanni, B, Borg, A, Brauch, H, Brenner, H, Burwinkel, B, Buys, SS, Caldés, T, Caligo, MA, Campa, D, Carter, BD, Castelao, JE, Chang-Claude, J, Chanock, SJ, Chung, WK, Claes, KBM, Clarke, CL, GEMO Study Collaborators, EMBRACE Collaborators, Collée, JM, Conroy, DM, Czene, K, Daly, MB, Devilee, P, Diez, O, Ding, YC, Domchek, SM, Dörk, T, Dos-Santos-Silva, I, Dunning, AM, Dwek, M, Eccles, DM, Eliassen, AH, Engel, C, Eriksson, M, Evans, DG, Fasching, PA, Flyger, H, Fostira, F, Friedman, E, Fritschi, L, Frost, D, Gago-Dominguez, M, Gapstur, SM, Garber, J, Garcia-Barberan, V, García-Closas, M, García-Sáenz, JA, Gaudet, MM, Gayther, SA, Gehrig, A, Georgoulias, V, Giles, GG, Godwin, AK, Goldberg, MS, Goldgar, DE, González-Neira, A, Greene, MH, Guénel, P, Haeberle, L, Hahnen, E, Haiman, CA, Håkansson, N, Hall, P, Hamann, U, Harrington, PA, Hart, SN, He, W, Hogervorst, FBL, Hollestelle, A, Hopper, JL, Horcasitas, DJ, Hulick, PJ, Hunter, DJ, Imyanitov, EN, KConFab Investigators, HEBON Investigators, ABCTB Investigators, Jager, A, Jakubowska, A, James, PA, Jensen, UB, John, EM, Jones, ME, Kaaks, R, Kapoor, PM, Karlan, BY, Keeman, R, Khusnutdinova, E, Kiiski, JI, Ko, Y-D, Kosma, V-M, Kraft, P, Kurian, AW, Laitman, Y, Lambrechts, D, Le Marchand, L, Lester, J, Lesueur, F, Lindstrom, T, Lopez-Fernández, A, Loud, JT, Luccarini, C, Mannermaa, A, Manoukian, S, Margolin, S, Martens, JWM, Mebirouk, N, Meindl, A, Miller, A, Milne, RL, Montagna, M, Nathanson, KL, Neuhausen, SL, Nevanlinna, H, Nielsen, FC, O'Brien, KM, Olopade, OI, Olson, JE, Olsson, H, Osorio, A, Ottini, L, Park-Simon, T-W, Parsons, MT, Pedersen, IS, Peshkin, B, Peterlongo, P, Peto, J, Pharoah, PDP, Phillips, K-A, Polley, EC, Poppe, B, Presneau, N, Pujana, MA, Punie, K, Radice, P, Rantala, J, Rashid, MU, Rennert, G, Rennert, HS, Robson, M, Romero, A, Rossing, M, Saloustros, E, Sandler, DP, Santella, R, Scheuner, MT, Schmidt, MK, Schmidt, G, Scott, C, Sharma, P, Soucy, P, Southey, MC, Spinelli, JJ, Steinsnyder, Z, Stone, J, Stoppa-Lyonnet, D, Swerdlow, A, Tamimi, RM, Tapper, WJ, Taylor, JA, Terry, MB, Teulé, A, Thull, DL, Tischkowitz, M, Toland, AE, Torres, D, Trainer, AH, Truong, T, Tung, N, Vachon, CM, Vega, A, Vijai, J, Wang, Q, Wappenschmidt, B, Weinberg, CR, Weitzel, JN, Wendt, C, Wolk, A, Yadav, S, Yang, XR, Yannoukakos, D, Zheng, W, Ziogas, A, Zorn, KK, Park, SK, Thomassen, M, Offit, K, Schmutzler, RK, Couch, FJ, Simard, J, Chenevix-Trench, G, Easton, DF, Andrieu, N, Antoniou, AC, Coignard, J, Lush, M, Beesley, J, O'Mara, TA, Dennis, J, Tyrer, JP, Barnes, DR, McGuffog, L, Leslie, G, Bolla, MK, Adank, MA, Agata, S, Ahearn, T, Aittomäki, K, Andrulis, IL, Anton-Culver, H, Arndt, V, Arnold, N, Aronson, KJ, Arun, BK, Augustinsson, A, Azzollini, J, Barrowdale, D, Baynes, C, Becher, H, Bermisheva, M, Bernstein, L, Białkowska, K, Blomqvist, C, Bojesen, SE, Bonanni, B, Borg, A, Brauch, H, Brenner, H, Burwinkel, B, Buys, SS, Caldés, T, Caligo, MA, Campa, D, Carter, BD, Castelao, JE, Chang-Claude, J, Chanock, SJ, Chung, WK, Claes, KBM, Clarke, CL, GEMO Study Collaborators, EMBRACE Collaborators, Collée, JM, Conroy, DM, Czene, K, Daly, MB, Devilee, P, Diez, O, Ding, YC, Domchek, SM, Dörk, T, Dos-Santos-Silva, I, Dunning, AM, Dwek, M, Eccles, DM, Eliassen, AH, Engel, C, Eriksson, M, Evans, DG, Fasching, PA, Flyger, H, Fostira, F, Friedman, E, Fritschi, L, Frost, D, Gago-Dominguez, M, Gapstur, SM, Garber, J, Garcia-Barberan, V, García-Closas, M, García-Sáenz, JA, Gaudet, MM, Gayther, SA, Gehrig, A, Georgoulias, V, Giles, GG, Godwin, AK, Goldberg, MS, Goldgar, DE, González-Neira, A, Greene, MH, Guénel, P, Haeberle, L, Hahnen, E, Haiman, CA, Håkansson, N, Hall, P, Hamann, U, Harrington, PA, Hart, SN, He, W, Hogervorst, FBL, Hollestelle, A, Hopper, JL, Horcasitas, DJ, Hulick, PJ, Hunter, DJ, Imyanitov, EN, KConFab Investigators, HEBON Investigators, ABCTB Investigators, Jager, A, Jakubowska, A, James, PA, Jensen, UB, John, EM, Jones, ME, Kaaks, R, Kapoor, PM, Karlan, BY, Keeman, R, Khusnutdinova, E, Kiiski, JI, Ko, Y-D, Kosma, V-M, Kraft, P, Kurian, AW, Laitman, Y, Lambrechts, D, Le Marchand, L, Lester, J, Lesueur, F, Lindstrom, T, Lopez-Fernández, A, Loud, JT, Luccarini, C, Mannermaa, A, Manoukian, S, Margolin, S, Martens, JWM, Mebirouk, N, Meindl, A, Miller, A, Milne, RL, Montagna, M, Nathanson, KL, Neuhausen, SL, Nevanlinna, H, Nielsen, FC, O'Brien, KM, Olopade, OI, Olson, JE, Olsson, H, Osorio, A, Ottini, L, Park-Simon, T-W, Parsons, MT, Pedersen, IS, Peshkin, B, Peterlongo, P, Peto, J, Pharoah, PDP, Phillips, K-A, Polley, EC, Poppe, B, Presneau, N, Pujana, MA, Punie, K, Radice, P, Rantala, J, Rashid, MU, Rennert, G, Rennert, HS, Robson, M, Romero, A, Rossing, M, Saloustros, E, Sandler, DP, Santella, R, Scheuner, MT, Schmidt, MK, Schmidt, G, Scott, C, Sharma, P, Soucy, P, Southey, MC, Spinelli, JJ, Steinsnyder, Z, Stone, J, Stoppa-Lyonnet, D, Swerdlow, A, Tamimi, RM, Tapper, WJ, Taylor, JA, Terry, MB, Teulé, A, Thull, DL, Tischkowitz, M, Toland, AE, Torres, D, Trainer, AH, Truong, T, Tung, N, Vachon, CM, Vega, A, Vijai, J, Wang, Q, Wappenschmidt, B, Weinberg, CR, Weitzel, JN, Wendt, C, Wolk, A, Yadav, S, Yang, XR, Yannoukakos, D, Zheng, W, Ziogas, A, Zorn, KK, Park, SK, Thomassen, M, Offit, K, Schmutzler, RK, Couch, FJ, Simard, J, Chenevix-Trench, G, Easton, DF, Andrieu, N, and Antoniou, AC
Abstract: A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-23162-4.
Published: 2021

46. Uluslararasi Iliskiler: Editorial

Author: Brauch H. G., Spring Ú. O., Aydın, M., Brauch H. G., Spring Ú. O., and Aydın, M.
Abstract: [No abstract available]
Published: 2021

47. CYP2D6-Tamoxifen: Pharmakogenetik beim frühen Mammakarzinom

Author: Brauch, H. and Schroth, W.
Published: 2010
Full Text: View/download PDF

48. Breast Cancer Polygenic Risk Score and Contralateral Breast Cancer Risk

Author: Kramer, I., Hooning, M.J., Mavaddat, N., Hauptmann, M., Keeman, R., Steyerberg, E.W., Giardiello, D., Antoniou, A.C., Pharoah, P.D.P., Canisius, S., Abu-Ful, Z., Andrulis, I.L., Anton-Culver, H., Aronson, K.J., Augustinsson, A., Becher, H., Beckmann, M.W., Behrens, S., Benitez, J., Bermisheva, M., Bogdanova, N.V., Bojesen, S.E., Bolla, M.K., Bonanni, B., Brauch, H., Bremer, M., Brucker, S.Y., Burwinkel, B., Castelao, J.E., Chan, T.L., Chang-Claude, J., Chanock, S.J., Chenevix-Trench, G., Choi, J.Y., Clarke, C.L., Collee, J.M., Couch, F.J., Cox, A., Cross, S.S., Czene, K., Daly, M.B., Devilee, P., Dork, T., dos-Santos-Silva, I., Dunning, A.M., Dwek, M., Eccles, D.M., Evans, D.G., Fasching, P.A., Flyger, H., Gago-Dominguez, M., Garcia-Closas, M., Garcia-Saenz, J.A., Giles, G.G., Goldgar, D.E., Gonzalez-Neira, A., Haiman, C.A., Hakansson, N., Hamann, U., Hartman, M., Heemskerk-Gerritsen, B.A.M., Hollestelle, A., Hopper, J.L., Hou, M.F., Howell, A., Ito, H., Jakimovska, M., Jakubowska, A., Janni, W., John, E.M., Jung, A., Kang, D., Kets, C.M., Khusnutdinova, E., Ko, Y.D., Kristensen, V.N., Kurian, A.W., Kwong, A., Lambrechts, D., Marchand, L. le, Li, J.M., Lindblom, A., Mannermaa, A., Manoochehri, M., Margolin, S., Matsuo, K., Mavroudis, D., Meindl, A., Milne, R.L., Mulligan, A.M., Muranen, T.A., Neuhausen, S.L., Nevanlinna, H., Newman, W.G., Olshan, A.F., Olson, J.E., Olsson, H., Park-Simon, T.W., Peto, J., Petridis, C., Plaseska-Karanfilska, D., Presneau, N., Pylkas, K., Radice, P., Rennert, G., Romero, A., Roylance, R., Saloustros, E., Sawyer, E.J., Schmutzler, R.K., Schwentner, L., Scott, C., See, M.H., Shah, M., Shen, C.Y., Shu, X.O., Siesling, S., Slager, S., Sohn, C., Southey, M.C., Spinelli, J.J., Stone, J., Tapper, W.J., Tengstrom, M., Teo, S.H., Terry, M.B., Tollenaar, R.A.E.M., Tomlinson, I., Troester, M.A., Vachon, C.M., Ongeval, C. van, Veen, E.M. van, Winqvist, R., Wolk, A., Zheng, W., Ziogas, A., Easton, D.F., Hall, P., Schmidt, M.K., NBCS Collaborators, ABCTB Investigators, and kConFab Investigators
Subjects: parasitic diseases
Abstract: Previous research has shown that polygenic risk scores (PRSs) can be used to stratify women according to their risk of developing primary invasive breast cancer. This study aimed to evaluate the association between a recently validated PRS of 313 germline variants (PRS313) and contralateral breast cancer (CBC) risk. We included 56,068 women of European ancestry diagnosed with first invasive breast cancer from 1990 onward with follow-up from the Breast Cancer Association Consortium. Metachronous CBC risk (N = 1,027) according to the distribution of PRS313 was quantified using Cox regression analyses. We assessed PRS313 interaction with age at first diagnosis, family history, morphology, ER status, PR status, and HER2 status, and (neo)adjuvant therapy. In studies of Asian women, with limited follow-up, CBC risk associated with PRS313 was assessed using logistic regression for 340 women with CBC compared with 12,133 women with unilateral breast cancer. Higher PRS313 was associated with increased CBC risk: hazard ratio per standard deviation (SD) = 1.25 (95%CI = 1.18-1.33) for Europeans, and an OR per SD = 1.15 (95%CI = 1.02-1.29) for Asians. The absolute lifetime risks of CBC, accounting for death as competing risk, were 12.4% for European women at the 10th percentile and 20.5% at the 90th percentile of PRS313. We found no evidence of confounding by or interaction with individual characteristics, characteristics of the primary tumor, or treatment. The C-index for the PRS313 alone was 0.563 (95%CI = 0.547-0.586). In conclusion, PRS313 is an independent factor associated with CBC risk and can be incorporated into CBC risk prediction models to help improve stratification and optimize surveillance and treatment strategies.
Published: 2020

49. Common variants in breast cancer risk loci predispose to distinct tumor subtypes

Author: 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, Børresen-Dale, A-L, Brauch, H, Brenner, H, Brooks-Wilson, A, Brüning, T, Burwinkel, B, Buys, SS, Canzian, F, Castelao, JE, Chang-Claude, J, Chanock, SJ, Chenevix-Trench, G, Clarke, CL, 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, Collée, JM, Cox, A, Cross, SS, Czene, K, Daly, MB, Devilee, P, Dörk, T, Dwek, M, Eccles, DM, Evans, DG, Fasching, PA, Figueroa, J, Floris, G, Gago-Dominguez, M, Gapstur, SM, García-Sáenz, JA, Gaudet, MM, Giles, GG, Goldberg, MS, González-Neira, A, Alnæs, GIG, Grip, M, Guénel, P, Haiman, CA, Hall, P, Hamann, U, Harkness, EF, Heemskerk-Gerritsen, BAM, Holleczek, B, Hollestelle, A, Hooning, MJ, Hoover, RN, Hopper, JL, Howell, A, Clarke, C, Balleine, R, Baxter, R, Braye, S, Carpenter, J, Dahlstrom, J, Forbes, J, Lee, C, Marsh, D, Morey, A, Pathmanathan, N, Scott, R, Simpson, P, Spigelman, A, Wilcken, N, Yip, D, Zeps, N, Fox, S, Campbell, I, Bowtell, D, Spurdle, A, Webb, P, de Fazio, A, Tassell, M, Kirk, J, Lindeman, G, Price, M, Southey, M, Milne, R, Deb, S, 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, Krüger, 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, AV, Peto, J, Pita, G, Plaseska-Karanfilska, D, Prentice, R, Punie, K, Pylkäs, K, Radice, P, Rennert, G, Romero, A, Rüdiger, T, Saloustros, E, Sampson, S, Sandler, DP, Sawyer, EJ, Schmutzler, RK, Schoemaker, MJ, Schöttker, 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, García-Closas, M, Chatterjee, N, Ahearn, Thomas U [0000-0003-0771-7752], Easton, Douglas [0000-0003-2444-3247], Pharoah, Paul [0000-0001-8494-732X], Apollo - University of Cambridge Repository, Medicum, HUS Comprehensive Cancer Center, Department of Oncology, Clinicum, Department of Obstetrics and Gynecology, Biosciences, HUS Gynecology and Obstetrics, Clinical Genetics, Medical Oncology, and Pathology
Subjects: False discovery rate, Oncology, Common breast cancer susceptibility variants, Receptor, ErbB-2, Estrogen receptor, PROGRESSION, Etiologic heterogeneity, Logistic regression, Basic medicine, Breast cancer, 0302 clinical medicine, PRIMARY THERAPY, HETEROGENEITY, RC254-282, HISTOLOGICAL GRADE, 0303 health sciences, Breast Neoplasms/epidemiology, Receptors, Estrogen/genetics, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, INTERNATIONAL EXPERT CONSENSUS, humanities, Receptor, ErbB-2/genetics, 3. Good health, Receptors, Estrogen, Receptors, Progesterone/genetics, 030220 oncology & carcinogenesis, Female, Biomarkers, Tumor/genetics, Receptors, Progesterone, Medical Genetics, Research Article, Risk, medicine.medical_specialty, SUSCEPTIBILITY LOCI, 3122 Cancers, Breast Neoplasms, Single-nucleotide polymorphism, Biology, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Internal medicine, Progesterone receptor, Biomarkers, Tumor, medicine, Genetic predisposition, Humans, ddc:610, GENOME-WIDE ASSOCIATION, Genetic association, Medicinsk genetik, 030304 developmental biology, Cancer och onkologi, medicine.disease, Cancer and Oncology, Clinical medicine, Genome-Wide Association Study
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 p 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.
Published: 2020

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

Author: Zhang, H, Ahearn, TU, Lecarpentier, J, Barnes, D, Beesley, J, Qi, G, Jiang, X, O’Mara, TA, Zhao, N, Bolla, MK, Dunning, AM, Dennis, J, Wang, Q, Ful, ZA, Aittomäki, K, Andrulis, IL, Anton-Culver, H, Arndt, V, Aronson, KJ, Arun, BK, Auer, PL, Azzollini, J, Barrowdale, D, Becher, H, Beckmann, MW, Behrens, S, Benitez, J, Bermisheva, M, Bialkowska, K, Blanco, A, Blomqvist, C, Bogdanova, NV, Bojesen, SE, Bonanni, B, Bondavalli, D, Borg, A, Brauch, H, Brenner, H, Briceno, I, Broeks, A, Brucker, SY, Brüning, T, Burwinkel, B, Buys, SS, Byers, H, Caldés, T, Caligo, MA, Calvello, M, Campa, D, Castelao, JE, Chang-Claude, J, Chanock, SJ, Christiaens, M, Christiansen, H, Chung, WK, Claes, KBM, Clarke, CL, Cornelissen, S, Couch, FJ, Cox, A, Cross, SS, Czene, K, Daly, MB, Devilee, P, Diez, O, Domchek, SM, Dörk, T, Dwek, M, Eccles, DM, Ekici, AB, Evans, DG, Fasching, PA, Figueroa, J, Foretova, L, Fostira, F, Friedman, E, Frost, D, Gago-Dominguez, M, Gapstur, SM, Garber, J, García-Sáenz, JA, Gaudet, MM, Gayther, SA, Giles, GG, Godwin, AK, Goldberg, MS, Goldgar, DE, González-Neira, A, Greene, MH, Gronwald, J, Guénel, P, Häberle, L, Hahnen, E, Haiman, CA, Hake, CR, Hall, P, Hamann, U, Harkness, EF, Heemskerk-Gerritsen, BAM, Hillemanns, P, Hogervorst, FBL, Holleczek, B, Hollestelle, A, Hooning, MJ, Hoover, RN, Hopper, JL, Howell, A, Huebner, H, Hulick, PJ, Imyanitov, EN, Isaacs, C, Izatt, L, Jager, A, Jakimovska, M, Jakubowska, A, James, P, Janavicius, R, Janni, W, John, EM, Jones, ME, Jung, A, Kaaks, R, Kapoor, PM, Karlan, BY, Keeman, R, Khan, S, Khusnutdinova, E, Kitahara, CM, Ko, Y-D, Konstantopoulou, I, Koppert, LB, Koutros, S, Kristensen, VN, Laenkholm, A-V, Lambrechts, D, Larsson, SC, Laurent-Puig, P, Lazaro, C, Lazarova, E, Lejbkowicz, F, Leslie, G, Lesueur, F, Lindblom, A, Lissowska, J, Lo, W-Y, Loud, JT, Lubinski, J, Lukomska, A, MacInnis, RJ, Mannermaa, A, Manoochehri, M, Manoukian, S, Margolin, S, Martinez, ME, Matricardi, L, McGuffog, L, McLean, C, Mebirouk, N, Meindl, A, Menon, U, Miller, A, Mingazheva, E, Montagna, M, Mulligan, AM, Mulot, C, Muranen, TA, Nathanson, KL, Neuhausen, SL, Nevanlinna, H, Neven, P, Newman, WG, Nielsen, FC, Nikitina-Zake, L, Nodora, J, Offit, K, Olah, E, Olopade, OI, Olsson, H, Orr, N, Papi, L, Papp, J, Park-Simon, T-W, Parsons, MT, Peissel, B, Peixoto, A, Peshkin, B, Peterlongo, P, Peto, J, Phillips, K-A, Piedmonte, M, Plaseska-Karanfilska, D, Prajzendanc, K, Prentice, R, Prokofyeva, D, Rack, B, Radice, P, Ramus, SJ, Rantala, J, Rashid, MU, Rennert, G, Rennert, HS, Risch, HA, Romero, A, Rookus, MA, Rübner, M, Rüdiger, T, Saloustros, E, Sampson, S, Sandler, DP, Sawyer, EJ, Scheuner, MT, Schmutzler, RK, Schneeweiss, A, Schoemaker, MJ, Schöttker, B, Schürmann, P, Senter, L, Sharma, P, Sherman, ME, Shu, X-O, Singer, CF, Smichkoska, S, Soucy, P, Southey, MC, Spinelli, JJ, Stone, J, Stoppa-Lyonnet, D, Swerdlow, AJ, Szabo, CI, Tamimi, RM, Tapper, WJ, Taylor, JA, Teixeira, MR, Terry, M, Thomassen, M, Thull, DL, Tischkowitz, M, Toland, AE, Tollenaar, RAEM, Tomlinson, I, Torres, D, Troester, MA, Truong, T, Tung, N, Untch, M, Vachon, CM, van den Ouweland, AMW, van der Kolk, LE, van Veen, EM, vanRensburg, EJ, Vega, A, Wappenschmidt, B, Weinberg, CR, Weitzel, JN, Wildiers, H, Winqvist, R, Wolk, A, Yang, XR, Yannoukakos, D, Zheng, W, Zorn, KK, Milne, RL, Kraft, P, Simard, J, Pharoah, PDP, Michailidou, K, Antoniou, AC, Schmidt, MK, Chenevix-Trench, G, Easton, DF, Chatterjee, N, and García-Closas, M
Abstract: Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype1,2,3. To identify novel loci, we performed a genome-wide association study including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. We identified 32 novel susceptibility loci (P
Published: 2020

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