Author: "Couch, F." - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Couch, F."' showing total 368 results

Start Over Author "Couch, F."

368 results on '"Couch, F."'

1. Risk-reducing mastectomy and breast cancer mortality in women with a BRCA1 or BRCA2 pathogenic variant: an international analysis

Author: Metcalfe, K, Huzarski, T, Gronwald, J, Kotsopoulos, J, Kim, R, Moller, P, Pal, T, Aeilts, A, Eisen, A, Karlan, B, Bordeleau, L, Tung, N, Olopade, O, Zakalik, D, Singer, C, Foulkes, W, Couch, F, Neuhausen, S, Eng, C, Sun, P, Lubinski, J, Narod, S, Velsher, L, Poll, A, Warner, E, Mccuaig, J, Armel, S, Saal, H, Steele, L, Lemire, E, Serfas, K, Senter, L, Sweet, K, Panchal, S, Cullinane, C, Blum, J, Rayson, D, Ramon y Cajal, T, Dungan, J, Fruscio, R, Zovato, S, Cohen, S, Metcalfe K., Huzarski T., Gronwald J., Kotsopoulos J., Kim R., Moller P., Pal T., Aeilts A., Eisen A., Karlan B., Bordeleau L., Tung N., Olopade O., Zakalik D., Singer C. F., Foulkes W., Couch F., Neuhausen S. L., Eng C., Sun P., Lubinski J., Narod S. A., Velsher L., Poll A., Warner E., McCuaig J., Armel S., Saal H., Steele L., Lemire E., Serfas K., Senter L., Sweet K., Panchal S., Cullinane C. A., Blum J. L., Rayson D., Ramon y Cajal T., Dungan J., Fruscio R., Zovato S., Cohen S., Metcalfe, K, Huzarski, T, Gronwald, J, Kotsopoulos, J, Kim, R, Moller, P, Pal, T, Aeilts, A, Eisen, A, Karlan, B, Bordeleau, L, Tung, N, Olopade, O, Zakalik, D, Singer, C, Foulkes, W, Couch, F, Neuhausen, S, Eng, C, Sun, P, Lubinski, J, Narod, S, Velsher, L, Poll, A, Warner, E, Mccuaig, J, Armel, S, Saal, H, Steele, L, Lemire, E, Serfas, K, Senter, L, Sweet, K, Panchal, S, Cullinane, C, Blum, J, Rayson, D, Ramon y Cajal, T, Dungan, J, Fruscio, R, Zovato, S, Cohen, S, Metcalfe K., Huzarski T., Gronwald J., Kotsopoulos J., Kim R., Moller P., Pal T., Aeilts A., Eisen A., Karlan B., Bordeleau L., Tung N., Olopade O., Zakalik D., Singer C. F., Foulkes W., Couch F., Neuhausen S. L., Eng C., Sun P., Lubinski J., Narod S. A., Velsher L., Poll A., Warner E., McCuaig J., Armel S., Saal H., Steele L., Lemire E., Serfas K., Senter L., Sweet K., Panchal S., Cullinane C. A., Blum J. L., Rayson D., Ramon y Cajal T., Dungan J., Fruscio R., Zovato S., and Cohen S.
Abstract: Background: Risk-reducing mastectomy (RRM) is offered to women with a BRCA1 or BRCA2 pathogenic variant, however, there are limited data on the impact on breast cancer mortality. Methods: Participants were identified from a registry of women with BRCA1/2 pathogenic variants. We used a pseudo-randomised trial design and matched one woman with a RRM to one woman without a RRM on year of birth, gene, and country. We estimated the hazard ratio (HR) and 95% confidence intervals (CI) for dying of breast cancer in the follow-up period. Results: There were 1654 women included; 827 assigned to the RRM arm and 827 assigned to the control arm. After a mean follow-up of 6.3 years, there were 20 incident breast cancers (including 15 occult cancers) and two breast cancer deaths in the RRM arm, and 100 incident breast cancers and 7 breast cancer deaths in the control arm (HR = 0.26; 95% CI 0.05–1.35; p = 0.11). The probability of dying of breast cancer within 15 years after RRM was 0.95%. Conclusions: In women with a BRCA1 or BRCA2 pathogenic variant, RRM reduces the risk of breast cancer, and the probability of dying of breast cancer is low.
Published: 2024

2. Bilateral Oophorectomy and All-Cause Mortality in Women With BRCA1 and BRCA2 Sequence Variations

Author: Kotsopoulos, J, Gronwald, J, Huzarski, T, Møller, P, Pal, T, Mccuaig, J, Singer, C, Karlan, B, Aeilts, A, Eng, C, Eisen, A, Bordeleau, L, Foulkes, W, Tung, N, Couch, F, Fruscio, R, Neuhausen, S, Zakalik, D, Cybulski, C, Metcalfe, K, Olopade, O, Sun, P, Lubinski, J, Narod, S, Kotsopoulos, Joanne, Gronwald, Jacek, Huzarski, Tomasz, Møller, Pål, Pal, Tuya, McCuaig, Jeanna M, Singer, Christian F, Karlan, Beth Y, Aeilts, Amber, Eng, Charis, Eisen, Andrea, Bordeleau, Louise, Foulkes, William D, Tung, Nadine, Couch, Fergus J, Fruscio, Robert, Neuhausen, Susan L, Zakalik, Dana, Cybulski, Cezary, Metcalfe, Kelly, Olopade, Olufunmilayo I, Sun, Ping, Lubinski, Jan, Narod, Steven A, Kotsopoulos, J, Gronwald, J, Huzarski, T, Møller, P, Pal, T, Mccuaig, J, Singer, C, Karlan, B, Aeilts, A, Eng, C, Eisen, A, Bordeleau, L, Foulkes, W, Tung, N, Couch, F, Fruscio, R, Neuhausen, S, Zakalik, D, Cybulski, C, Metcalfe, K, Olopade, O, Sun, P, Lubinski, J, Narod, S, Kotsopoulos, Joanne, Gronwald, Jacek, Huzarski, Tomasz, Møller, Pål, Pal, Tuya, McCuaig, Jeanna M, Singer, Christian F, Karlan, Beth Y, Aeilts, Amber, Eng, Charis, Eisen, Andrea, Bordeleau, Louise, Foulkes, William D, Tung, Nadine, Couch, Fergus J, Fruscio, Robert, Neuhausen, Susan L, Zakalik, Dana, Cybulski, Cezary, Metcalfe, Kelly, Olopade, Olufunmilayo I, Sun, Ping, Lubinski, Jan, and Narod, Steven A
Abstract: IMPORTANCE Preventive bilateral salpingo-oophorectomy is offered to women at high risk of ovarian cancer who carry a pathogenic variant in BRCA1 or BRCA2; however, the association of oophorectomy with all-cause mortality has not been clearly defined. OBJECTIVE To evaluate the association between bilateral oophorectomy and all-cause mortality among women with a BRCA1 or BRCA2 sequence variation. DESIGN, SETTING, AND PARTICIPANTS In this international, longitudinal cohort study ofwomen with BRCA sequence variations, information on bilateral oophorectomy was obtained via biennial questionnaire. Participants were women with a BRCA1 or BRCA2 sequence variation, no prior history of cancer, and at least 1 follow-up questionnaire completed. Women were followed up from age 35 to 75 years for incident cancers and deaths. Cox proportional hazards regression was used to estimate the hazard ratios (HRs) and 95% CIs for all-cause mortality associated with a bilateral oophorectomy (time dependent). Data analysis was performed from January 1 to June 1, 2023. EXPOSURES Self-reported bilateral oophorectomy (with or without salpingectomy). MAIN OUTCOMES AND MEASURES All-cause mortality, breast cancer-specific mortality, and ovarian cancer-specific mortality. RESULTS There were 4332 women (mean age, 42.6 years) enrolled in the cohort, of whom 2932 (67.8%) chose to undergo a preventive oophorectomy at a mean (range) age of 45.4 (23.0-77.0) years. After a mean follow-up of 9.0 years, 851 women had developed cancer and 228 had died; 57 died of ovarian or fallopian tube cancer, 58 died of breast cancer, 16 died of peritoneal cancer, and 97 died of other causes. The age-adjusted HR for all-cause mortality associated with oophorectomy was 0.32 (95% CI, 0.24-0.42; P < .001). The age-adjusted HR was 0.28 (95% CI, 0.20-0.38; P < .001) and 0.43 (95% CI, 0.22-0.90; P = .03) for women with BRCA1 and BRCA2 sequence variations, respectively. For women with BRCA1 sequence variations, the estima
Published: 2024

3. MRI Surveillance and Breast Cancer Mortality in Women With BRCA1 and BRCA2 Sequence Variations

Author: Lubinski, J, Kotsopoulos, J, Moller, P, Pal, T, Eisen, A, Peck, L, Karlan, B, Aeilts, A, Eng, C, Bordeleau, L, Foulkes, W, Tung, N, Couch, F, Fruscio, R, Ramon Y Cajal, T, Singer, C, Neuhausen, S, Zakalik, D, Cybulski, C, Gronwald, J, Huzarski, T, Stempa, K, Dungan, J, Cullinane, C, Olopade, O, Metcalfe, K, Sun, P, Narod, S, Lubinski, Jan, Kotsopoulos, Joanne, Moller, Pal, Pal, Tuya, Eisen, Andrea, Peck, Larissa, Karlan, Beth Y, Aeilts, Amber, Eng, Charis, Bordeleau, Louise, Foulkes, William D, Tung, Nadine, Couch, Fergus J, Fruscio, Robert, Ramon Y Cajal, Teresa, Singer, Christian F, Neuhausen, Susan L, Zakalik, Dana, Cybulski, Cezary, Gronwald, Jacek, Huzarski, Tomasz, Stempa, Klaudia, Dungan, Jeffrey, Cullinane, Carey, Olopade, Olufunmilayo I, Metcalfe, Kelly, Sun, Ping, Narod, Steven A, Lubinski, J, Kotsopoulos, J, Moller, P, Pal, T, Eisen, A, Peck, L, Karlan, B, Aeilts, A, Eng, C, Bordeleau, L, Foulkes, W, Tung, N, Couch, F, Fruscio, R, Ramon Y Cajal, T, Singer, C, Neuhausen, S, Zakalik, D, Cybulski, C, Gronwald, J, Huzarski, T, Stempa, K, Dungan, J, Cullinane, C, Olopade, O, Metcalfe, K, Sun, P, Narod, S, Lubinski, Jan, Kotsopoulos, Joanne, Moller, Pal, Pal, Tuya, Eisen, Andrea, Peck, Larissa, Karlan, Beth Y, Aeilts, Amber, Eng, Charis, Bordeleau, Louise, Foulkes, William D, Tung, Nadine, Couch, Fergus J, Fruscio, Robert, Ramon Y Cajal, Teresa, Singer, Christian F, Neuhausen, Susan L, Zakalik, Dana, Cybulski, Cezary, Gronwald, Jacek, Huzarski, Tomasz, Stempa, Klaudia, Dungan, Jeffrey, Cullinane, Carey, Olopade, Olufunmilayo I, Metcalfe, Kelly, Sun, Ping, and Narod, Steven A
Abstract: IMPORTANCE Magnetic resonance imaging (MRI) surveillance is offered to women with a pathogenic variant in the BRCA1 or BRCA2 gene who face a high lifetime risk of breast cancer. Surveillance with MRI is effective in downstaging breast cancers, but the association of MRI surveillance with mortality risk has not been well defined. OBJECTIVE To compare breast cancer mortality rates in women with a BRCA1 or BRCA2 sequence variation who entered an MRI surveillance program with those who did not. DESIGN, SETTING, AND PARTICIPANTS Women with a BRCA1 or BRCA2 sequence variation were identified from 59 participating centers in 11 countries. Participants completed a baseline questionnaire between 1995 and 2015 and a follow-up questionnaire every 2 years to document screening histories, incident cancers, and vital status. Women who had breast cancer, a screening MRI examination, or bilateral mastectomy prior to enrollment were excluded. Participants were followed up from age 30 years (or the date of the baseline questionnaire, whichever was later) until age 75 years, the last follow-up, or death from breast cancer. Data were analyzed from January 1 to July 31, 2023. EXPOSURES Entrance into an MRI surveillance program. MAIN OUTCOMES AND MEASURES Cox proportional hazards modelingwas used to estimate the hazard ratios (HRs) and 95% CIs for breast cancer mortality associated with MRI surveillance compared with no MRI surveillance using a time-dependent analysis. RESULTS A total of 2488 women (mean [range] age at study entry 41.2 [30-69] years), with a sequence variation in the BRCA1 (n = 2004) or BRCA2 (n = 484) genes were included in the analysis. Of these participants, 1756 (70.6%) had at least 1 screening MRI examination and 732 women (29.4%) did not. After a mean follow-up of 9.2 years, 344 women (13.8%) developed breast cancer and 35 women (1.4%) died of breast cancer. The age-adjusted HRs for breast cancer mortality associated with entering an MRI surveillance program were 0
Published: 2024

4. 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

5. Mammographic density and risk of breast cancer by age and tumor characteristics

Author: Cummings, Steven, Kerlikowske, Karla, Bertrand, KA, Tamimi, RM, Scott, CG, Jensen, MR, Pankratz, VS, Visscher, D, Norman, A, Couch, F, Shepherd, J, and Fan, B
Abstract: Introduction: Understanding whether mammographic density (MD) is associated with all breast tumor subtypes and whether the strength of association varies by age is important for utilizing MD in risk models.Methods: Data were pooled from six studies includi
Published: 2013

6. Rapid progression of prostate cancer in men with a BRCA2 mutation.

Author: Narod, SA, Neuhausen, S, Vichodez, G, Armel, S, Lynch, HT, Ghadirian, P, Cummings, S, Olopade, O, Stoppa-Lyonnet, D, Couch, F, Wagner, T, Warner, E, Foulkes, WD, Saal, H, Weitzel, J, Tulman, A, Poll, A, Nam, R, Sun, P, Hereditary Breast Cancer Study Group, Danquah, Jessica, Domchek, Susan, Tung, Nadine, Ainsworth, Peter, Horsman, Douglas, Kim-Sing, Charmaine, Maugard, Christine, Eisen, Andrea, Daly, Mary, McKinnon, Wendy, Wood, Marie, Isaacs, Claudine, Gilchrist, Dawna, Karlan, Beth, Nedelcu, Raluca, Meschino, Wendy, Garber, Judy, Pasini, Barbara, Manoukian, Siranoush, and Bellati, Christina
Subjects: Hereditary Breast Cancer Study Group, Humans, Prostatic Neoplasms, Disease Progression, Genetic Predisposition to Disease, Heterozygote, Mutation, Genes, BRCA1, Genes, BRCA2, Adult, Aged, Aged, 80 and over, Middle Aged, Male, prostate cancer, BRCA1, BRCA2, Genes, and over, Oncology and Carcinogenesis, Public Health and Health Services, Oncology & Carcinogenesis
Abstract: Men with BRCA2 mutations have been found to be at increased risk of developing prostate cancer. There is a recent report that BRCA2 carriers with prostate cancer have poorer survival than noncarrier prostate cancer patients. In this study, we compared survival of men with a BRCA2 mutation and prostate cancer with that of men with a BRCA1 mutation and prostate cancer. We obtained the age at diagnosis, age at death or current age from 182 men with prostate cancer from families with a BRCA2 mutation and from 119 men with prostate cancer from families with a BRCA1 mutation. The median survival from diagnosis was 4.0 years for men with a BRCA2 mutation vs 8.0 years for men with a BRCA1 mutation, and the difference was highly significant (P
Published: 2008

7. The risks of cancer in older women with BRCA pathogenic variants: How far have we come?

Author: Metcalfe, K, Gronwald, J, Tung, N, Mccuaig, J, Eisen, A, Elser, C, Foulkes, W, Neuhausen, S, Senter, L, Moller, P, Bordeleau, L, Fruscio, R, Velsher, L, Zakalik, D, Olopade, O, Eng, C, Pal, T, Cullinane, C, Couch, F, Kotsopoulos, J, Sun, P, Lubinski, J, Narod, S, Metcalfe K. A., Gronwald J., Tung N. M., McCuaig J. M., Eisen A., Elser C., Foulkes W. D., Neuhausen S. L., Senter L., Moller P., Bordeleau L., Fruscio R., Velsher L., Zakalik D., Olopade O. I., Eng C., Pal T., Cullinane C. A., Couch F. J., Kotsopoulos J., Sun P., Lubinski J., Narod S. A., Metcalfe, K, Gronwald, J, Tung, N, Mccuaig, J, Eisen, A, Elser, C, Foulkes, W, Neuhausen, S, Senter, L, Moller, P, Bordeleau, L, Fruscio, R, Velsher, L, Zakalik, D, Olopade, O, Eng, C, Pal, T, Cullinane, C, Couch, F, Kotsopoulos, J, Sun, P, Lubinski, J, Narod, S, Metcalfe K. A., Gronwald J., Tung N. M., McCuaig J. M., Eisen A., Elser C., Foulkes W. D., Neuhausen S. L., Senter L., Moller P., Bordeleau L., Fruscio R., Velsher L., Zakalik D., Olopade O. I., Eng C., Pal T., Cullinane C. A., Couch F. J., Kotsopoulos J., Sun P., Lubinski J., and Narod S. A.
Abstract: Background: The purpose of this study was to estimate the cumulative risks of all cancers in women from 50 to 75 years of age with a BRCA1 or BRCA2 pathogenic variant. Methods: Participants were women with BRCA1 or BRCA2 pathogenic variants from 85 centers in 16 countries. Women were eligible if they had no cancer before the age of 50 years. Participants completed a baseline questionnaire and follow-up questionnaires every 2 years. Women were followed from age 50 until a diagnosis of cancer, death, age 75, or last follow-up. The risk of all cancers combined from age 50 to 75 was estimated using the Kaplan-Meier method. Results: There were 2211 women included (1470 BRCA1 and 742 BRCA2). There were 379 cancers diagnosed in the cohort between 50 and 75 years. The actuarial risk of any cancer from age 50 to 75 was 49% for BRCA1 and 43% for BRCA2. Breast (n = 186) and ovarian (n = 45) were the most frequent cancers observed. For women who had both risk-reducing mastectomy and bilateral salpingo-oophorectomy before age 50, the risk of developing any cancer between age 50 and 75 was 9%. Conclusion: Women with a BRCA1 or BRCA2 pathogenic variant have a high risk of cancer between the ages of 50 and 75 years and should be counselled appropriately.
Published: 2022

8. Gene‐panel testing of breast and ovarian cancer patients identifies a recurrent RAD51C duplication

Author: Pelttari, L.M., Shimelis, H., Toiminen, H., Kvist, A., Törngren, T., Borg, Å., Blomqvist, C., Bützow, R., Couch, F., Aittomäki, K., and Nevanlinna, H.
Published: 2018
Full Text: View/download PDF

9. Genome-wide and transcriptome-wide association studies of mammographic density phenotypes reveal novel loci

Author: Chen, H, Fan, S, Stone, J, Thompson, DJ, Douglas, J, Li, S, Scott, C, Bolla, MK, Wang, Q, Dennis, J, Michailidou, K, Li, C, Peters, U, Hopper, JL, Southey, MC, Nguyen-Dumont, T, Nguyen, TL, Fasching, PA, Behrens, A, Cadby, G, Murphy, RA, Aronson, K, Howell, A, Astley, S, Couch, F, Olson, J, Milne, RL, Giles, GG, Haiman, CA, Maskarinec, G, Winham, S, John, EM, Kurian, A, Eliassen, H, Andrulis, I, Evans, DG, Newman, WG, Hall, P, Czene, K, Swerdlow, A, Jones, M, Pollan, M, Fernandez-Navarro, P, McConnell, DS, Kristensen, VN, Rothstein, JH, Wang, P, Habel, LA, Sieh, W, Dunning, AM, Pharoah, PDP, Easton, DF, Gierach, GL, Tamimi, RM, Vachon, CM, Lindstrom, S, Chen, H, Fan, S, Stone, J, Thompson, DJ, Douglas, J, Li, S, Scott, C, Bolla, MK, Wang, Q, Dennis, J, Michailidou, K, Li, C, Peters, U, Hopper, JL, Southey, MC, Nguyen-Dumont, T, Nguyen, TL, Fasching, PA, Behrens, A, Cadby, G, Murphy, RA, Aronson, K, Howell, A, Astley, S, Couch, F, Olson, J, Milne, RL, Giles, GG, Haiman, CA, Maskarinec, G, Winham, S, John, EM, Kurian, A, Eliassen, H, Andrulis, I, Evans, DG, Newman, WG, Hall, P, Czene, K, Swerdlow, A, Jones, M, Pollan, M, Fernandez-Navarro, P, McConnell, DS, Kristensen, VN, Rothstein, JH, Wang, P, Habel, LA, Sieh, W, Dunning, AM, Pharoah, PDP, Easton, DF, Gierach, GL, Tamimi, RM, Vachon, CM, and Lindstrom, S
Abstract: BACKGROUND: Mammographic density (MD) phenotypes, including percent density (PMD), area of dense tissue (DA), and area of non-dense tissue (NDA), are associated with breast cancer risk. Twin studies suggest that MD phenotypes are highly heritable. However, only a small proportion of their variance is explained by identified genetic variants. METHODS: We conducted a genome-wide association study, as well as a transcriptome-wide association study (TWAS), of age- and BMI-adjusted DA, NDA, and PMD in up to 27,900 European-ancestry women from the MODE/BCAC consortia. RESULTS: We identified 28 genome-wide significant loci for MD phenotypes, including nine novel signals (5q11.2, 5q14.1, 5q31.1, 5q33.3, 5q35.1, 7p11.2, 8q24.13, 12p11.2, 16q12.2). Further, 45% of all known breast cancer SNPs were associated with at least one MD phenotype at p < 0.05. TWAS further identified two novel genes (SHOX2 and CRISPLD2) whose genetically predicted expression was significantly associated with MD phenotypes. CONCLUSIONS: Our findings provided novel insight into the genetic background of MD phenotypes, and further demonstrated their shared genetic basis with breast cancer.
Published: 2022

10. 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

11. Rare germline copy number variants (CNVs) and breast cancer risk

Author: Dennis, J. (Joe), Tyrer, J. P. (Jonathan P.), Walker, L. C. (Logan C.), Michailidou, K. (Kyriaki), Dorling, L. (Leila), Bolla, M. K. (Manjeet K.), Wang, Q. (Qin), Ahearn, T. U. (Thomas U.), Andrulis, I. L. (Irene L.), Anton-Culver, H. (Hoda), Antonenkova, N. N. (Natalia N.), Arndt, V. (Volker), Aronson, K. J. (Kristan J.), Freeman, L. E. (Laura E. Beane), Beckmann, M. W. (Matthias W.), Behrens, S. (Sabine), Benitez, J. (Javier), Bermisheva, M. (Marina), Bogdanova, N. V. (Natalia, V), Bojesen, S. E. (Stig E.), Brenner, H. (Hermann), Castelao, J. E. (Jose E.), Chang-Claude, J. (Jenny), Chenevix-Trench, G. (Georgia), Clarke, C. L. (Christine L.), N. C. (NBCS Collaborators), Collee, J. M. (J. Margriet), C. C. (CTS Consortium), Couch, F. J. (Fergus J.), Cox, A. (Angela), Cross, S. S. (Simon S.), Czene, K. (Kamila), Devilee, P. (Peter), Dörk, T. (Thilo), Dossus, L. (Laure), Eliassen, A. H. (A. Heather), Eriksson, M. (Mikael), Evans, D. G. (D. Gareth), Fasching, P. A. (Peter A.), Figueroa, J. (Jonine), Fletcher, O. (Olivia), Flyger, H. (Henrik), Fritschi, L. (Lin), Gabrielson, M. (Marike), Gago-Dominguez, M. (Manuela), Garcia-Closas, M. (Montserrat), Giles, G. G. (Graham G.), Gonzalez-Neira, A. (Anna), Guenel, P. (Pascal), Hahnen, E. (Eric), Haiman, C. A. (Christopher A.), Hall, P. (Per), Hollestelle, A. (Antoinette), Hoppe, R. (Reiner), Hopper, J. L. (John L.), Howell, A. (Anthony), A. I. (ABCTB Investigators), k. I. (kConFab/AOCS Investigators), Jager, A. (Agnes), Jakubowska, A. (Anna), John, E. M. (Esther M.), Johnson, N. (Nichola), Jones, M. E. (Michael E.), Jung, A. (Audrey), Kaaks, R. (Rudolf), Keeman, R. (Renske), Khusnutdinova, E. (Elza), Kitahara, C. M. (Cari M.), Ko, Y.-D. (Yon-Dschun), Kosma, V.-M. (Veli-Matti), Koutros, S. (Stella), Kraft, P. (Peter), Kristensen, V. N. (Vessela N.), Kubelka-Sabit, K. (Katerina), Kurian, A. W. (Allison W.), Lacey, J. V. (James, V), Lambrechts, D. (Diether), Larson, N. L. (Nicole L.), Linet, M. (Martha), Ogrodniczak, A. (Alicja), Mannermaa, A. (Arto), Manoukian, S. (Siranoush), Margolin, S. (Sara), Mavroudis, D. (Dimitrios), Milne, R. L. (Roger L.), Muranen, T. A. (Taru A.), Murphy, R. A. (Rachel A.), Nevanlinna, H. (Heli), Olson, J. E. (Janet E.), Olsson, H. (Hakan), Park-Simon, T.-W. (Tjoung-Won), Perou, C. M. (Charles M.), Peterlongo, P. (Paolo), Plaseska-Karanfilska, D. (Dijana), Pylkas, K. (Katri), Rennert, G. (Gad), Saloustros, E. (Emmanouil), Sandler, D. P. (Dale P.), Sawyer, E. J. (Elinor J.), Schmidt, M. K. (Marjanka K.), Schmutzler, R. K. (Rita K.), Shibli, R. (Rana), Smeets, A. (Ann), Soucy, P. (Penny), Southey, M. C. (Melissa C.), Swerdlow, A. J. (Anthony J.), Tamimi, R. M. (Rulla M.), Taylor, J. A. (Jack A.), Teras, L. R. (Lauren R.), Terry, M. B. (Mary Beth), Tomlinson, I. (Ian), Troester, M. A. (Melissa A.), Truong, T. (Therese), Vachon, C. M. (Celine M.), Wendt, C. (Camilla), Winqvist, R. (Robert), Wolk, A. (Alicja), Yang, X. R. (Xiaohong R.), Zheng, W. (Wei), Ziogas, A. (Argyrios), Simard, J. (Jacques), Dunning, A. M. (Alison M.), Pharoah, P. D. (Paul D. P.), Easton, D. F. (Douglas F.), Dennis, J. (Joe), Tyrer, J. P. (Jonathan P.), Walker, L. C. (Logan C.), Michailidou, K. (Kyriaki), Dorling, L. (Leila), Bolla, M. K. (Manjeet K.), Wang, Q. (Qin), Ahearn, T. U. (Thomas U.), Andrulis, I. L. (Irene L.), Anton-Culver, H. (Hoda), Antonenkova, N. N. (Natalia N.), Arndt, V. (Volker), Aronson, K. J. (Kristan J.), Freeman, L. E. (Laura E. Beane), Beckmann, M. W. (Matthias W.), Behrens, S. (Sabine), Benitez, J. (Javier), Bermisheva, M. (Marina), Bogdanova, N. V. (Natalia, V), Bojesen, S. E. (Stig E.), Brenner, H. (Hermann), Castelao, J. E. (Jose E.), Chang-Claude, J. (Jenny), Chenevix-Trench, G. (Georgia), Clarke, C. L. (Christine L.), N. C. (NBCS Collaborators), Collee, J. M. (J. Margriet), C. C. (CTS Consortium), Couch, F. J. (Fergus J.), Cox, A. (Angela), Cross, S. S. (Simon S.), Czene, K. (Kamila), Devilee, P. (Peter), Dörk, T. (Thilo), Dossus, L. (Laure), Eliassen, A. H. (A. Heather), Eriksson, M. (Mikael), Evans, D. G. (D. Gareth), Fasching, P. A. (Peter A.), Figueroa, J. (Jonine), Fletcher, O. (Olivia), Flyger, H. (Henrik), Fritschi, L. (Lin), Gabrielson, M. (Marike), Gago-Dominguez, M. (Manuela), Garcia-Closas, M. (Montserrat), Giles, G. G. (Graham G.), Gonzalez-Neira, A. (Anna), Guenel, P. (Pascal), Hahnen, E. (Eric), Haiman, C. A. (Christopher A.), Hall, P. (Per), Hollestelle, A. (Antoinette), Hoppe, R. (Reiner), Hopper, J. L. (John L.), Howell, A. (Anthony), A. I. (ABCTB Investigators), k. I. (kConFab/AOCS Investigators), Jager, A. (Agnes), Jakubowska, A. (Anna), John, E. M. (Esther M.), Johnson, N. (Nichola), Jones, M. E. (Michael E.), Jung, A. (Audrey), Kaaks, R. (Rudolf), Keeman, R. (Renske), Khusnutdinova, E. (Elza), Kitahara, C. M. (Cari M.), Ko, Y.-D. (Yon-Dschun), Kosma, V.-M. (Veli-Matti), Koutros, S. (Stella), Kraft, P. (Peter), Kristensen, V. N. (Vessela N.), Kubelka-Sabit, K. (Katerina), Kurian, A. W. (Allison W.), Lacey, J. V. (James, V), Lambrechts, D. (Diether), Larson, N. L. (Nicole L.), Linet, M. (Martha), Ogrodniczak, A. (Alicja), Mannermaa, A. (Arto), Manoukian, S. (Siranoush), Margolin, S. (Sara), Mavroudis, D. (Dimitrios), Milne, R. L. (Roger L.), Muranen, T. A. (Taru A.), Murphy, R. A. (Rachel A.), Nevanlinna, H. (Heli), Olson, J. E. (Janet E.), Olsson, H. (Hakan), Park-Simon, T.-W. (Tjoung-Won), Perou, C. M. (Charles M.), Peterlongo, P. (Paolo), Plaseska-Karanfilska, D. (Dijana), Pylkas, K. (Katri), Rennert, G. (Gad), Saloustros, E. (Emmanouil), Sandler, D. P. (Dale P.), Sawyer, E. J. (Elinor J.), Schmidt, M. K. (Marjanka K.), Schmutzler, R. K. (Rita K.), Shibli, R. (Rana), Smeets, A. (Ann), Soucy, P. (Penny), Southey, M. C. (Melissa C.), Swerdlow, A. J. (Anthony J.), Tamimi, R. M. (Rulla M.), Taylor, J. A. (Jack A.), Teras, L. R. (Lauren R.), Terry, M. B. (Mary Beth), Tomlinson, I. (Ian), Troester, M. A. (Melissa A.), Truong, T. (Therese), Vachon, C. M. (Celine M.), Wendt, C. (Camilla), Winqvist, R. (Robert), Wolk, A. (Alicja), Yang, X. R. (Xiaohong R.), Zheng, W. (Wei), Ziogas, A. (Argyrios), Simard, J. (Jacques), Dunning, A. M. (Alison M.), Pharoah, P. D. (Paul D. P.), and Easton, D. F. (Douglas F.)
Abstract: Germline copy number variants (CNVs) are pervasive in the human genome but potential disease associations with rare CNVs have not been comprehensively assessed in large datasets. We analysed rare CNVs in genes and non-coding regions for 86,788 breast cancer cases and 76,122 controls of European ancestry with genome-wide array data. Gene burden tests detected the strongest association for deletions in BRCA1 (P = 3.7E-18). Nine other genes were associated with a p-value < 0.01 including known susceptibility genes CHEK2 (P = 0.0008), ATM (P = 0.002) and BRCA2 (P = 0.008). Outside the known genes we detected associations with p-values < 0.001 for either overall or subtype-specific breast cancer at nine deletion regions and four duplication regions. Three of the deletion regions were in established common susceptibility loci. To the best of our knowledge, this is the first genome-wide analysis of rare CNVs in a large breast cancer case-control dataset. We detected associations with exonic deletions in established breast cancer susceptibility genes. We also detected suggestive associations with non-coding CNVs in known and novel loci with large effects sizes. Larger sample sizes will be required to reach robust levels of statistical significance.
Published: 2022

12. Bilateral Oophorectomy and the Risk of Breast Cancer in BRCA1 Mutation Carriers: a Reappraisal

Author: Kotsopoulos, J, Lubiński, J, Gronwald, J, Menkiszak, J, Mccuaig, J, Metcalfe, K, Foulkes, W, Neuhausen, S, Sun, S, Karlan, B, Eisen, A, Tung, N, Olopade, O, Couch, F, Huzarski, T, Senter, L, Bordeleau, L, Singer, C, Eng, C, Fruscio, R, Pal, T, Sun, P, Narod, S, Kotsopoulos, Joanne, Lubiński, Jan, Gronwald, Jacek, Menkiszak, Janusz, McCuaig, Jeanna, Metcalfe, Kelly, Foulkes, William D, Neuhausen, Susan L, Sun, Sophie, Karlan, Beth Y, Eisen, Andrea, Tung, Nadine, Olopade, Olufunmilayo I, Couch, Fergus J, Huzarski, Tomasz, Senter, Leigha, Bordeleau, Louise, Singer, Christian F, Eng, Charis, Fruscio, Robert, Pal, Tuya, Sun, Ping, Narod, Steven A, Kotsopoulos, J, Lubiński, J, Gronwald, J, Menkiszak, J, Mccuaig, J, Metcalfe, K, Foulkes, W, Neuhausen, S, Sun, S, Karlan, B, Eisen, A, Tung, N, Olopade, O, Couch, F, Huzarski, T, Senter, L, Bordeleau, L, Singer, C, Eng, C, Fruscio, R, Pal, T, Sun, P, Narod, S, Kotsopoulos, Joanne, Lubiński, Jan, Gronwald, Jacek, Menkiszak, Janusz, McCuaig, Jeanna, Metcalfe, Kelly, Foulkes, William D, Neuhausen, Susan L, Sun, Sophie, Karlan, Beth Y, Eisen, Andrea, Tung, Nadine, Olopade, Olufunmilayo I, Couch, Fergus J, Huzarski, Tomasz, Senter, Leigha, Bordeleau, Louise, Singer, Christian F, Eng, Charis, Fruscio, Robert, Pal, Tuya, Sun, Ping, and Narod, Steven A
Abstract: Background: The lack of consensus on whether bilateral oophorectomy impacts risk of developing breast cancer among BRCA1 mutation carriers might be attributed to various biases, specifically, cancer-induced testing bias due to inclusion of prevalent cases. We conducted two complementary matched case-control analyses to evaluate the association of oophorectomy and BRCA1 breast cancer. Methods: A research questionnaire was administered every two years to collect information on exposures and disease. In the first analysis, we limited the study to prevalent breast cancer cases (diagnosed prior to study entry; n = 2,962) who were matched to controls on year of birth and country of residence (n=4,358). In the second approach, we limited to 330 incident cases (diagnosed in the follow-up period) and 1,548 matched controls. Conditional logistic regression was used to estimate the adjusted odds ratios (OR) and 95% confidence intervals (CI) of invasive breast cancer. Results: In the first approach, there was a significant inverse association between oophorectomy and the risk of developing breast cancer [OR = 0.43; 95% confidence interval (CI), 0.34- 0.55; P < 00001]. In the second approach, there was no association between oophorectomy and risk (OR = 1.21; 95% CI, 0.87-1.70; P = 0.26). Conclusions: The inclusion of women with a personal history of breast cancer prior to ascertainment likely impacts upon the association of oophorectomy and BRCA1 breast cancer risk. Impact: Oophorectomy is unlikely a determinant of breast cancer risk in BRCA1 mutation carriers but should be offered at age 35 to reduce the risk of ovarian and fallopian tube cancer.
Published: 2022

13. Genetic counselorsʼ practices and confidence regarding variant of uncertain significance results and reclassification from BRCA testing

Author: Scherr, C. L., Lindor, N. M., Malo, T. L., Couch, F. J., and Vadaparampil, S. T.
Published: 2015
Full Text: View/download PDF

14. First international workshop of the ATM and Cancer Risk Group (4–5 December 2019)

Author: Lesueur, F., Easton, D. F., Renault, A. -L., Tavtigian, S. V., Bernstein, J. L., Kote-Jarai, Z., Eeles, R. A., Plaseska-Karanfia, D., Feliubadalo, L., Moles-Fernandez, A., Santamarina-Pena, M., Sanchez, A. T., Lopez-Novo, A., Porras, L. -M., Blanco, A., Capella, G., de la Hoya, M., Molina, I. J., Osorio, A., Pineda, M., Rueda, D., de la Cruz, X., Diez, O., Ruiz-Ponte, C., Gutierrez-Enriquez, S., Vega, A., Lazaro, C., Arun, B., Herold, N., Versmold, B., Schmutzler, R. K., Nguyen-Dumont, T., Southey, M. C., Dorling, L., Dunning, A. M., Ghiorzo, P., Dalmasso, B. S., Cavaciuti, E., Le Gal, D., Roberts, N. J., Dominguez-Valentin, M., Rookus, M., Taylor, A. M. R., Goldstein, A. M., Goldgar, D. E., Couch, F., Kraft, P., Weitzel, J., Nathanson, K., Domchek, S., Laduca, H., Stoppa-Lyonnet, D., and Andrieu, N.
Subjects: 0301 basic medicine, Cancer Research, medicine.medical_specialty, Heterozygote, Variants classification, ATM, Cancer risk, Cancer spectrum, Tumor profiles, Population, Context (language use), Breast Neoplasms, Ataxia Telangiectasia Mutated Proteins, 030105 genetics & heredity, Article, 03 medical and health sciences, Ataxia Telangiectasia, 0302 clinical medicine, Neoplasms, Epidemiology, Genetics, medicine, Humans, Genetic Predisposition to Disease, education, Genetics (clinical), education.field_of_study, business.industry, Cancer, medicine.disease, Oncology, 030220 oncology & carcinogenesis, Family medicine, Female, France, business
Abstract: The first International Workshop of the ATM and Cancer Risk group focusing on the role of Ataxia-Telangiectasia Mutated (ATM) gene in cancer was held on December 4 and 5, 2019 at Institut Curie in Paris, France. It was motivated by the fact that germline ATM pathogenic variants have been found to be associated with different cancer types. However, due to the lack of precise age-, sex-, and site-specific risk estimates, no consensus on management guidelines for variant carriers exists, and the clinical utility of ATM variant testing is uncertain. The meeting brought together epidemiologists, geneticists, biologists and clinicians to review current knowledge and on-going challenges related to ATM and cancer risk. This report summarizes the meeting sessions content that covered the latest results in family-based and population-based studies, the importance of accurate variant classification, the effect of radiation exposures for ATM variant carriers, and the characteristics of ATM-deficient tumors. The report concludes that ATM variant carriers outside of the context of Ataxia-Telangiectasia may benefit from effective cancer risk management and therapeutic strategies and that efforts to set up large-scale studies in the international framework to achieve this goal are necessary.
Published: 2021

15. BRCA1 and BRCA2 genetic testing—pitfalls and recommendations for managing variants of uncertain clinical significance

Author: Eccles, D. M., Mitchell, G., Monteiro, A. N. A., Schmutzler, R., Couch, F. J., Spurdle, A. B., Gómez-García, E. B., Driessen, R., Lindor, N.M., Blok, M.J., Moller, P., de la Hoya, M., Pal, T., Domchek, S., Nathanson, K., Van Asperen, C., Diez, O., Rheim, K., Stoppa-Lyonnet, D., Parsons, M., and Goldgar, D.
Published: 2015
Full Text: View/download PDF

16. 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

17. First international workshop of the ATM and cancer risk group (4-5 December 2019).

Author: Lesueur F., Easton D.F., Renault A.-L., Tavtigian S.V., Bernstein J.L., Kote-Jarai Z., Eeles R.A., Plaseska-Karanfia D., Feliubadalo L., Moles-Fernandez A., Santamarina-Pena M., Sanchez A.T., Lopez-Novo A., Porras L.-M., Blanco A., Capella G., de la Hoya M., Molina I.J., Osorio A., Pineda M., Rueda D., de la Cruz X., Diez O., Ruiz-Ponte C., Gutierrez-Enriquez S., Vega A., Lazaro C., Arun B., Herold N., Versmold B., Schmutzler R.K., Nguyen-Dumont T., Southey M.C., Dorling L., Dunning A.M., Ghiorzo P., Dalmasso B.S., Cavaciuti E., Le Gal D., Roberts N.J., Dominguez-Valentin M., Rookus M., Taylor A.M.R., Goldstein A.M., Goldgar D.E., Couch F., Kraft P., Weitzel J., Nathanson K., Domchek S., LaDuca H., Stoppa-Lyonnet D., Andrieu N., Lesueur F., Easton D.F., Renault A.-L., Tavtigian S.V., Bernstein J.L., Kote-Jarai Z., Eeles R.A., Plaseska-Karanfia D., Feliubadalo L., Moles-Fernandez A., Santamarina-Pena M., Sanchez A.T., Lopez-Novo A., Porras L.-M., Blanco A., Capella G., de la Hoya M., Molina I.J., Osorio A., Pineda M., Rueda D., de la Cruz X., Diez O., Ruiz-Ponte C., Gutierrez-Enriquez S., Vega A., Lazaro C., Arun B., Herold N., Versmold B., Schmutzler R.K., Nguyen-Dumont T., Southey M.C., Dorling L., Dunning A.M., Ghiorzo P., Dalmasso B.S., Cavaciuti E., Le Gal D., Roberts N.J., Dominguez-Valentin M., Rookus M., Taylor A.M.R., Goldstein A.M., Goldgar D.E., Couch F., Kraft P., Weitzel J., Nathanson K., Domchek S., LaDuca H., Stoppa-Lyonnet D., and Andrieu N.
Abstract: The first International Workshop of the ATM and Cancer Risk group focusing on the role of Ataxia-Telangiectasia Mutated (ATM) gene in cancer was held on December 4 and 5, 2019 at Institut Curie in Paris, France. It was motivated by the fact that germline ATM pathogenic variants have been found to be associated with different cancer types. However, due to the lack of precise age-, sex-, and site-specific risk estimates, no consensus on management guidelines for variant carriers exists, and the clinical utility of ATM variant testing is uncertain. The meeting brought together epidemiologists, geneticists, biologists and clinicians to review current knowledge and on-going challenges related to ATM and cancer risk. This report summarizes the meeting sessions content that covered the latest results in family-based and population-based studies, the importance of accurate variant classification, the effect of radiation exposures for ATM variant carriers, and the characteristics of ATM-deficient tumors. The report concludes that ATM variant carriers outside of the context of Ataxia-Telangiectasia may benefit from effective cancer risk management and therapeutic strategies and that efforts to set up large-scale studies in the international framework to achieve this goal are necessary.Copyright © 2021, The Author(s), under exclusive licence to Springer Nature B.V.
Published: 2021

18. Gene-environment interactions relevant to estrogen and risk of breast cancer:can gene-environment interactions be detected only among candidate SNPs from genome-wide association studies?

Author: Park, J. (JooYong), Choi, J.-Y. (Ji-Yeob), Choi, J. (Jaesung), Chung, S. (Seokang), Song, N. (Nan), Park, S. K. (Sue K.), Han, W. (Wonshik), Noh, D.-Y. (Dong-Young), Ahn, S.-H. (Sei-Hyun), Lee, J. W. (Jong Won), Kim, M. K. (Mi Kyung), Jee, S. H. (Sun Ha), Wen, W. (Wanqing), Bolla, M. K. (Manjeet K.), Wang, Q. (Qin), Dennis, J. (Joe), Michailidou, K. (Kyriaki), Shah, M. (Mitul), Conroy, D. M. (Don M.), Harrington, P. A. (Patricia A.), Mayes, R. (Rebecca), Czene, K. (Kamila), Hall, P. (Per), Teras, L. R. (Lauren R.), Patel, A. V. (Alpa V.), Couch, F. J. (Fergus J.), Olson, J. E. (Janet E.), Sawyer, E. J. (Elinor J.), Roylance, R. (Rebecca), Bojesen, S. E. (Stig E.), Flyger, H. (Henrik), Lambrechts, D. (Diether), Baten, A. (Adinda), Matsuo, K. (Keitaro), Ito, H. (Hidemi), Guenel, P. (Pascal), Truong, T. (Therese), Keeman, R. (Renske), Schmidt, M. K. (Marjanka K.), Wu, A. H. (Anna H.), Tseng, C.-C. (Chiu-Chen), Cox, A. (Angela), Cross, S. S. (Simon S.), Andrulis, I. L. (Irene L.), Hopper, J. L. (John L.), Southey, M. C. (Melissa C.), Wu, P.-E. (Pei-Ei), Shen, C.-Y. (Chen-Yang), Fasching, P. A. (Peter A.), Ekici, A. B. (Arif B.), Muir, K. (Kenneth), Lophatananon, A. (Artitaya), Brenner, H. (Hermann), Arndt, V. (Volker), Jones, M. E. (Michael E.), Swerdlow, A. J. (Anthony J.), Hoppe, R. (Reiner), Ko, Y.-D. (Yon-Dschun), Hartman, M. (Mikael), Li, J. (Jingmei), Mannermaa, A. (Arto), Hartikainen, J. M. (Jaana M.), Benitez, J. (Javier), Gonzalez-Neira, A. (Anna), Haiman, C. A. (Christopher A.), Doerk, T. (Thilo), Bogdanova, N. V. (Natalia V.), Teo, S. H. (Soo Hwang), Mohd Taib, N. A. (Nur Aishah), Fletcher, O. (Olivia), Johnson, N. (Nichola), Grip, M. (Mervi), Winqvist, R. (Robert), Blomqvist, C. (Carl), Nevanlinna, H. (Heli), Lindblom, A. (Annika), Wendt, C. (Camilla), Kristensen, V. N. (Vessela N.), Tollenaar, R. A. (Rob A. E. M.), Heemskerk-Gerritsen, B. A. (Bernadette A. M.), Radice, P. (Paolo), Bonanni, B. (Bernardo), Hamann, U. (Ute), Manoochehri, M. (Mehdi), Lacey, J. V. (James V.), Martinez, M. E. (Maria Elena), Dunning, A. M. (Alison M.), Pharoah, P. D. (Paul D. P.), Easton, D. F. (Douglas F.), Yoo, K.-Y. (Keun-Young), Kang, D. (Daehee), Park, J. (JooYong), Choi, J.-Y. (Ji-Yeob), Choi, J. (Jaesung), Chung, S. (Seokang), Song, N. (Nan), Park, S. K. (Sue K.), Han, W. (Wonshik), Noh, D.-Y. (Dong-Young), Ahn, S.-H. (Sei-Hyun), Lee, J. W. (Jong Won), Kim, M. K. (Mi Kyung), Jee, S. H. (Sun Ha), Wen, W. (Wanqing), Bolla, M. K. (Manjeet K.), Wang, Q. (Qin), Dennis, J. (Joe), Michailidou, K. (Kyriaki), Shah, M. (Mitul), Conroy, D. M. (Don M.), Harrington, P. A. (Patricia A.), Mayes, R. (Rebecca), Czene, K. (Kamila), Hall, P. (Per), Teras, L. R. (Lauren R.), Patel, A. V. (Alpa V.), Couch, F. J. (Fergus J.), Olson, J. E. (Janet E.), Sawyer, E. J. (Elinor J.), Roylance, R. (Rebecca), Bojesen, S. E. (Stig E.), Flyger, H. (Henrik), Lambrechts, D. (Diether), Baten, A. (Adinda), Matsuo, K. (Keitaro), Ito, H. (Hidemi), Guenel, P. (Pascal), Truong, T. (Therese), Keeman, R. (Renske), Schmidt, M. K. (Marjanka K.), Wu, A. H. (Anna H.), Tseng, C.-C. (Chiu-Chen), Cox, A. (Angela), Cross, S. S. (Simon S.), Andrulis, I. L. (Irene L.), Hopper, J. L. (John L.), Southey, M. C. (Melissa C.), Wu, P.-E. (Pei-Ei), Shen, C.-Y. (Chen-Yang), Fasching, P. A. (Peter A.), Ekici, A. B. (Arif B.), Muir, K. (Kenneth), Lophatananon, A. (Artitaya), Brenner, H. (Hermann), Arndt, V. (Volker), Jones, M. E. (Michael E.), Swerdlow, A. J. (Anthony J.), Hoppe, R. (Reiner), Ko, Y.-D. (Yon-Dschun), Hartman, M. (Mikael), Li, J. (Jingmei), Mannermaa, A. (Arto), Hartikainen, J. M. (Jaana M.), Benitez, J. (Javier), Gonzalez-Neira, A. (Anna), Haiman, C. A. (Christopher A.), Doerk, T. (Thilo), Bogdanova, N. V. (Natalia V.), Teo, S. H. (Soo Hwang), Mohd Taib, N. A. (Nur Aishah), Fletcher, O. (Olivia), Johnson, N. (Nichola), Grip, M. (Mervi), Winqvist, R. (Robert), Blomqvist, C. (Carl), Nevanlinna, H. (Heli), Lindblom, A. (Annika), Wendt, C. (Camilla), Kristensen, V. N. (Vessela N.), Tollenaar, R. A. (Rob A. E. M.), Heemskerk-Gerritsen, B. A. (Bernadette A. M.), Radice, P. (Paolo), Bonanni, B. (Bernardo), Hamann, U. (Ute), Manoochehri, M. (Mehdi), Lacey, J. V. (James V.), Martinez, M. E. (Maria Elena), Dunning, A. M. (Alison M.), Pharoah, P. D. (Paul D. P.), Easton, D. F. (Douglas F.), Yoo, K.-Y. (Keun-Young), and Kang, D. (Daehee)
Abstract: In this study we aim to examine gene–environment interactions (GxEs) between genes involved with estrogen metabolism and environmental factors related to estrogen exposure. GxE analyses were conducted with 1970 Korean breast cancer cases and 2052 controls in the case-control study, the Seoul Breast Cancer Study (SEBCS). A total of 11,555 SNPs from the 137 candidate genes were included in the GxE analyses with eight established environmental factors. A replication test was conducted by using an independent population from the Breast Cancer Association Consortium (BCAC), with 62,485 Europeans and 9047 Asians. The GxE tests were performed by using two-step methods in GxEScan software. Two interactions were found in the SEBCS. The first interaction was shown between rs13035764 of NCOA1 and age at menarche in the GE|2df model (p-2df = 1.2 × 10−3). The age at menarche before 14 years old was associated with the high risk of breast cancer, and the risk was higher when subjects had homozygous minor allele G. The second GxE was shown between rs851998 near ESR1 and height in the GE|2df model (p-2df = 1.1 × 10−4). Height taller than 160 cm was associated with a high risk of breast cancer, and the risk increased when the minor allele was added. The findings were not replicated in the BCAC. These results would suggest specificity in Koreans for breast cancer risk.
Published: 2021

19. Functional annotation of the 2q35 breast cancer risk locus implicates a structural variant in influencing activity of a long-range enhancer element

Author: Baxter, J. S. (Joseph S.), Johnson, N. (Nichola), Tomczyk, K. (Katarzyna), Gillespie, A. (Andrea), Maguire, S. (Sarah), Brough, R. (Rachel), Fachal, L. (Laura), 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), 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.), Brenner, H. (Hermann), Brucker, S. Y. (Sara Y.), Cai, Q. (Qiuyin), Campa, D. (Daniele), Canzian, F. (Federico), Castelao, J. E. (Jose E.), Chan, T. L. (Tsun L.), Chang-Claude, J. (Jenny), Chanock, S. J. (Stephen J.), Chenevix-Trench, G. (Georgia), Choi, J.-Y. (Ji-Yeob), Clarke, C. L. (Christine L.), Collaborators, N. (Nbcs), Colonna, S. (Sarah), 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), Doerk, T. (Thilo), Dossus, L. (Laure), Dwek, M. (Miriam), Eccles, D. M. (Diana M.), Ekici, A. B. (Arif B.), Eliassen, A. H. (A. Heather), Engel, C. (Christoph), Fasching, P. A. (Peter A.), Figueroa, J. (Jonine), Flyger, H. (Henrik), Gago-Dominguez, M. (Manuela), Gao, C. (Chi), Garcia-Closas, M. (Montserrat), Garcia-Saenz, J. A. (Jose A.), Ghoussaini, M. (Maya), Giles, G. G. (Graham G.), Goldberg, M. S. (Mark S.), Gonzalez-Neira, A. (Anna), Guenel, P. (Pascal), Guendert, M. (Melanie), Haeberle, L. (Lothar), Hahnen, E. (Eric), Haiman, C. A. (Christopher A.), Hall, P. (Per), Hamann, U. (Ute), Hartman, M. (Mikael), Hatse, S. (Sigrid), Hauke, J. (Jan), Hollestelle, A. (Antoinette), Hoppe, R. (Reiner), Hopper, J. L. (John L.), Hou, M.-F. (Ming-Feng), Ito, H. (Hidemi), Iwasaki, M. (Motoki), Jager, A. (Agnes), Jakubowska, A. (Anna), Janni, W. (Wolfgang), John, E. M. (Esther M.), Joseph, V. (Vijai), Jung, A. (Audrey), Kaaks, R. (Rudolf), Kang, D. (Daehee), Keeman, R. (Renske), Khusnutdinova, E. (Elza), Kim, S.-W. (Sung-Won), Kosma, V.-M. (Veli-Matti), Kraft, P. (Peter), Kristensen, V. N. (Vessela N.), Kubelka-Sabit, K. (Katerina), Kurian, A. W. (Allison W.), Kwong, A. (Ava), Lacey, J. V. (James, V), Lambrechts, D. (Diether), Larson, N. L. (Nicole L.), Larsson, S. C. (Susanna C.), Le Marchand, L. (Loic), Lejbkowicz, F. (Flavio), Li, J. (Jingmei), Long, J. (Jirong), Lophatananon, A. (Artitaya), LubiNski, J. (Jan), Mannermaa, A. (Arto), Manoochehri, M. (Mehdi), Manoukian, S. (Siranoush), Margolin, S. (Sara), Matsuo, K. (Keitaro), Mavroudis, D. (Dimitrios), Mayes, R. (Rebecca), Menon, U. (Usha), Milne, R. L. (Roger L.), Taib, N. A. (Nur Aishah Mohd), Muir, K. (Kenneth), Muranen, T. A. (Taru A.), Murphy, R. A. (Rachel A.), Nevanlinna, H. (Heli), O'Brien, K. M. (Katie M.), Offit, K. (Kenneth), Olson, J. E. (Janet E.), Olsson, H. (Hakan), Park, S. K. (Sue K.), Park-Simon, T.-W. (Tjoung-Won), Patel, A. V. (Alpa, V), Peterlongo, P. (Paolo), Peto, J. (Julian), Plaseska-Karanfilska, D. (Dijana), Presneau, N. (Nadege), Pylkäs, K. (Katri), Rack, B. (Brigitte), Rennert, G. (Gad), Romero, A. (Atocha), Ruebner, M. (Matthias), Ruediger, T. (Thomas), Saloustros, E. (Emmanouil), Sandler, D. P. (Dale P.), Sawyer, E. J. (Elinor J.), Schmidt, M. K. (Marjanka K.), Schmutzler, R. K. (Rita K.), Schneeweiss, A. (Andreas), Schoemaker, M. J. (Minouk J.), Shah, M. (Mitul), Shen, C.-Y. (Chen-Yang), Shu, X.-O. (Xiao-Ou), Simard, J. (Jacques), 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.), Taylor, J. A. (Jack A.), Teo, S. H. (Soo Hwang), Teras, L. R. (Lauren R.), Terry, M. B. (Mary Beth), Toland, A. E. (Amanda E.), Tomlinson, I. (Ian), Truong, T. (Therese), Tseng, C.-C. (Chiu-Chen), Untch, M. (Michael), Vachon, C. M. (Celine M.), van den Ouweland, A. M. (Ans M. W.), Wang, S. S. (Sophia S.), Weinberg, C. R. (Clarice R.), Wendt, C. (Camilla), Winham, S. J. (Stacey J.), Winqvist, R. (Robert), Wolk, A. (Alicja), Wu, A. H. (Anna H.), Yamaji, T. (Taiki), Zheng, W. (Wei), Ziogas, A. (Argyrios), Pharoah, P. D. (Paul D. P.), Dunning, A. M. (Alison M.), Easton, D. F. (Douglas F.), Pettitt, S. J. (Stephen J.), Lord, C. J. (Christopher J.), Haider, S. (Syed), Orr, N. (Nick), Fletcher, O. (Olivia), Baxter, J. S. (Joseph S.), Johnson, N. (Nichola), Tomczyk, K. (Katarzyna), Gillespie, A. (Andrea), Maguire, S. (Sarah), Brough, R. (Rachel), Fachal, L. (Laura), 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), 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.), Brenner, H. (Hermann), Brucker, S. Y. (Sara Y.), Cai, Q. (Qiuyin), Campa, D. (Daniele), Canzian, F. (Federico), Castelao, J. E. (Jose E.), Chan, T. L. (Tsun L.), Chang-Claude, J. (Jenny), Chanock, S. J. (Stephen J.), Chenevix-Trench, G. (Georgia), Choi, J.-Y. (Ji-Yeob), Clarke, C. L. (Christine L.), Collaborators, N. (Nbcs), Colonna, S. (Sarah), 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), Doerk, T. (Thilo), Dossus, L. (Laure), Dwek, M. (Miriam), Eccles, D. M. (Diana M.), Ekici, A. B. (Arif B.), Eliassen, A. H. (A. Heather), Engel, C. (Christoph), Fasching, P. A. (Peter A.), Figueroa, J. (Jonine), Flyger, H. (Henrik), Gago-Dominguez, M. (Manuela), Gao, C. (Chi), Garcia-Closas, M. (Montserrat), Garcia-Saenz, J. A. (Jose A.), Ghoussaini, M. (Maya), Giles, G. G. (Graham G.), Goldberg, M. S. (Mark S.), Gonzalez-Neira, A. (Anna), Guenel, P. (Pascal), Guendert, M. (Melanie), Haeberle, L. (Lothar), Hahnen, E. (Eric), Haiman, C. A. (Christopher A.), Hall, P. (Per), Hamann, U. (Ute), Hartman, M. (Mikael), Hatse, S. (Sigrid), Hauke, J. (Jan), Hollestelle, A. (Antoinette), Hoppe, R. (Reiner), Hopper, J. L. (John L.), Hou, M.-F. (Ming-Feng), Ito, H. (Hidemi), Iwasaki, M. (Motoki), Jager, A. (Agnes), Jakubowska, A. (Anna), Janni, W. (Wolfgang), John, E. M. (Esther M.), Joseph, V. (Vijai), Jung, A. (Audrey), Kaaks, R. (Rudolf), Kang, D. (Daehee), Keeman, R. (Renske), Khusnutdinova, E. (Elza), Kim, S.-W. (Sung-Won), Kosma, V.-M. (Veli-Matti), Kraft, P. (Peter), Kristensen, V. N. (Vessela N.), Kubelka-Sabit, K. (Katerina), Kurian, A. W. (Allison W.), Kwong, A. (Ava), Lacey, J. V. (James, V), Lambrechts, D. (Diether), Larson, N. L. (Nicole L.), Larsson, S. C. (Susanna C.), Le Marchand, L. (Loic), Lejbkowicz, F. (Flavio), Li, J. (Jingmei), Long, J. (Jirong), Lophatananon, A. (Artitaya), LubiNski, J. (Jan), Mannermaa, A. (Arto), Manoochehri, M. (Mehdi), Manoukian, S. (Siranoush), Margolin, S. (Sara), Matsuo, K. (Keitaro), Mavroudis, D. (Dimitrios), Mayes, R. (Rebecca), Menon, U. (Usha), Milne, R. L. (Roger L.), Taib, N. A. (Nur Aishah Mohd), Muir, K. (Kenneth), Muranen, T. A. (Taru A.), Murphy, R. A. (Rachel A.), Nevanlinna, H. (Heli), O'Brien, K. M. (Katie M.), Offit, K. (Kenneth), Olson, J. E. (Janet E.), Olsson, H. (Hakan), Park, S. K. (Sue K.), Park-Simon, T.-W. (Tjoung-Won), Patel, A. V. (Alpa, V), Peterlongo, P. (Paolo), Peto, J. (Julian), Plaseska-Karanfilska, D. (Dijana), Presneau, N. (Nadege), Pylkäs, K. (Katri), Rack, B. (Brigitte), Rennert, G. (Gad), Romero, A. (Atocha), Ruebner, M. (Matthias), Ruediger, T. (Thomas), Saloustros, E. (Emmanouil), Sandler, D. P. (Dale P.), Sawyer, E. J. (Elinor J.), Schmidt, M. K. (Marjanka K.), Schmutzler, R. K. (Rita K.), Schneeweiss, A. (Andreas), Schoemaker, M. J. (Minouk J.), Shah, M. (Mitul), Shen, C.-Y. (Chen-Yang), Shu, X.-O. (Xiao-Ou), Simard, J. (Jacques), 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.), Taylor, J. A. (Jack A.), Teo, S. H. (Soo Hwang), Teras, L. R. (Lauren R.), Terry, M. B. (Mary Beth), Toland, A. E. (Amanda E.), Tomlinson, I. (Ian), Truong, T. (Therese), Tseng, C.-C. (Chiu-Chen), Untch, M. (Michael), Vachon, C. M. (Celine M.), van den Ouweland, A. M. (Ans M. W.), Wang, S. S. (Sophia S.), Weinberg, C. R. (Clarice R.), Wendt, C. (Camilla), Winham, S. J. (Stacey J.), Winqvist, R. (Robert), Wolk, A. (Alicja), Wu, A. H. (Anna H.), Yamaji, T. (Taiki), Zheng, W. (Wei), Ziogas, A. (Argyrios), Pharoah, P. D. (Paul D. P.), Dunning, A. M. (Alison M.), Easton, D. F. (Douglas F.), Pettitt, S. J. (Stephen J.), Lord, C. J. (Christopher J.), Haider, S. (Syed), Orr, N. (Nick), and Fletcher, O. (Olivia)
Abstract: A combination of genetic and functional approaches has identified three independent breast cancer risk loci at 2q35. A recent fine-scale mapping analysis to refine these associations resulted in 1 (signal 1), 5 (signal 2), and 42 (signal 3) credible causal variants at these loci. We used publicly available in silico DNase I and ChIP-seq data with in vitro reporter gene and CRISPR assays to annotate signals 2 and 3. We identified putative regulatory elements that enhanced cell-type-specific transcription from the IGFBP5 promoter at both signals (30- to 40-fold increased expression by the putative regulatory element at signal 2, 2- to 3-fold by the putative regulatory element at signal 3). We further identified one of the five credible causal variants at signal 2, a 1.4 kb deletion (esv3594306), as the likely causal variant; the deletion allele of this variant was associated with an average additional increase in IGFBP5 expression of 1.3-fold (MCF-7) and 2.2-fold (T-47D). We propose a model in which the deletion allele of esv3594306 juxtaposes two transcription factor binding regions (annotated by estrogen receptor alpha ChIP-seq peaks) to generate a single extended regulatory element. This regulatory element increases cell-type-specific expression of the tumor suppressor gene IGFBP5 and, thereby, reduces risk of estrogen receptor-positive breast cancer (odds ratio = 0.77, 95% CI 0.74–0.81, p = 3.1 × 10−31).
Published: 2021

20. Germline variants and breast cancer survival in patients with distant metastases at primary breast cancer diagnosis

Author: Escala-Garcia, M. (Maria), Canisius, S. (Sander), Keeman, R. (Renske), Beesley, J. (Jonathan), Anton-Culver, H. (Hoda), Arndt, V. (Volker), Augustinsson, A. (Annelie), Becher, H. (Heiko), Beckmann, M. W. (Matthias W.), Behrens, S. (Sabine), Bermisheva, M. (Marina), Bojesen, S. E. (Stig E.), Bolla, M. K. (Manjeet K.), Brenner, H. (Hermann), Canzian, F. (Federico), Castelao, J. E. (Jose E.), Chang-Claude, J. (Jenny), Chanock, S. J. (Stephen J.), Couch, F. J. (Fergus J.), Czene, K. (Kamila), Daly, M. B. (Mary B.), Dennis, J. (Joe), Devilee, P. (Peter), Dork, T. (Thilo), Dunning, A. M. (Alison M.), Easton, D. F. (Douglas F.), Ekici, A. B. (Arif B.), Eliassen, A. H. (A. Heather), Fasching, P. A. (Peter A.), Flyger, H. (Henrik), Gago-Dominguez, M. (Manuela), Garcia-Closas, M. (Montserrat), Garcia-Saenz, J. A. (Jose A.), Geisler, J. (Juergen), Giles, G. G. (Graham G.), Grip, M. (Mervi), Guendert, M. (Melanie), Hahnen, E. (Eric), Haiman, C. A. (Christopher A.), Hakansson, N. (Niclas), Hall, P. (Per), Hamann, U. (Ute), Hartikainen, J. M. (Jaana M.), Heemskerk-Gerritsen, B. A. (Bernadette A. M.), Hollestelle, A. (Antoinette), Hoppe, R. (Reiner), Hopper, J. L. (John L.), Hunter, D. J. (David J.), Jacot, W. (William), Jakubowska, A. (Anna), John, E. M. (Esther M.), Jung, A. Y. (Audrey Y.), Kaaks, R. (Rudolf), Khusnutdinova, E. (Elza), Koppert, L. B. (Linetta B.), Kraft, P. (Peter), Kristensen, V. N. (Vessela N.), Kurian, A. W. (Allison W.), Lambrechts, D. (Diether), Le Marchand, L. (Loic), Lindblom, A. (Annika), Luben, R. N. (Robert N.), Lubinski, J. (Jan), Mannermaa, A. (Arto), Manoochehri, M. (Mehdi), Margolin, S. (Sara), Mavroudis, D. (Dimitrios), Muranen, T. A. (Taru A.), Nevanlinna, H. (Heli), Olshan, A. F. (Andrew F.), Olsson, H. (Hakan), Park-Simon, T.-W. (Tjoung-Won), Patel, A. V. (Alpa V.), Peterlongo, P. (Paolo), Pharoah, P. D. (Paul D. P.), Punie, K. (Kevin), Radice, P. (Paolo), Rennert, G. (Gad), Rennert, H. S. (Hedy S.), Romero, A. (Atocha), Roylance, R. (Rebecca), Ruediger, T. (Thomas), Ruebner, M. (Matthias), Saloustros, E. (Emmanouil), Sawyer, E. J. (Elinor J.), Schmutzler, R. K. (Rita K.), Schoemaker, M. J. (Minouk J.), Scott, C. (Christopher), Southey, M. C. (Melissa C.), Surowy, H. (Harald), Swerdlow, A. J. (Anthony J.), Tamimi, R. M. (Rulla M.), Teras, L. R. (Lauren R.), Thomas, E. (Emilie), Tomlinson, I. (Ian), Troester, M. A. (Melissa A.), Vachon, C. M. (Celine M.), Wang, Q. (Qin), Winqvist, R. (Robert), Wolk, A. (Alicja), Ziogas, A. (Argyrios), Michailidou, K. (Kyriaki), Chenevix-Trench, G. (Georgia), Bachelot, T. (Thomas), Schmidt, M. K. (Marjanka K.), Escala-Garcia, M. (Maria), Canisius, S. (Sander), Keeman, R. (Renske), Beesley, J. (Jonathan), Anton-Culver, H. (Hoda), Arndt, V. (Volker), Augustinsson, A. (Annelie), Becher, H. (Heiko), Beckmann, M. W. (Matthias W.), Behrens, S. (Sabine), Bermisheva, M. (Marina), Bojesen, S. E. (Stig E.), Bolla, M. K. (Manjeet K.), Brenner, H. (Hermann), Canzian, F. (Federico), Castelao, J. E. (Jose E.), Chang-Claude, J. (Jenny), Chanock, S. J. (Stephen J.), Couch, F. J. (Fergus J.), Czene, K. (Kamila), Daly, M. B. (Mary B.), Dennis, J. (Joe), Devilee, P. (Peter), Dork, T. (Thilo), Dunning, A. M. (Alison M.), Easton, D. F. (Douglas F.), Ekici, A. B. (Arif B.), Eliassen, A. H. (A. Heather), Fasching, P. A. (Peter A.), Flyger, H. (Henrik), Gago-Dominguez, M. (Manuela), Garcia-Closas, M. (Montserrat), Garcia-Saenz, J. A. (Jose A.), Geisler, J. (Juergen), Giles, G. G. (Graham G.), Grip, M. (Mervi), Guendert, M. (Melanie), Hahnen, E. (Eric), Haiman, C. A. (Christopher A.), Hakansson, N. (Niclas), Hall, P. (Per), Hamann, U. (Ute), Hartikainen, J. M. (Jaana M.), Heemskerk-Gerritsen, B. A. (Bernadette A. M.), Hollestelle, A. (Antoinette), Hoppe, R. (Reiner), Hopper, J. L. (John L.), Hunter, D. J. (David J.), Jacot, W. (William), Jakubowska, A. (Anna), John, E. M. (Esther M.), Jung, A. Y. (Audrey Y.), Kaaks, R. (Rudolf), Khusnutdinova, E. (Elza), Koppert, L. B. (Linetta B.), Kraft, P. (Peter), Kristensen, V. N. (Vessela N.), Kurian, A. W. (Allison W.), Lambrechts, D. (Diether), Le Marchand, L. (Loic), Lindblom, A. (Annika), Luben, R. N. (Robert N.), Lubinski, J. (Jan), Mannermaa, A. (Arto), Manoochehri, M. (Mehdi), Margolin, S. (Sara), Mavroudis, D. (Dimitrios), Muranen, T. A. (Taru A.), Nevanlinna, H. (Heli), Olshan, A. F. (Andrew F.), Olsson, H. (Hakan), Park-Simon, T.-W. (Tjoung-Won), Patel, A. V. (Alpa V.), Peterlongo, P. (Paolo), Pharoah, P. D. (Paul D. P.), Punie, K. (Kevin), Radice, P. (Paolo), Rennert, G. (Gad), Rennert, H. S. (Hedy S.), Romero, A. (Atocha), Roylance, R. (Rebecca), Ruediger, T. (Thomas), Ruebner, M. (Matthias), Saloustros, E. (Emmanouil), Sawyer, E. J. (Elinor J.), Schmutzler, R. K. (Rita K.), Schoemaker, M. J. (Minouk J.), Scott, C. (Christopher), Southey, M. C. (Melissa C.), Surowy, H. (Harald), Swerdlow, A. J. (Anthony J.), Tamimi, R. M. (Rulla M.), Teras, L. R. (Lauren R.), Thomas, E. (Emilie), Tomlinson, I. (Ian), Troester, M. A. (Melissa A.), Vachon, C. M. (Celine M.), Wang, Q. (Qin), Winqvist, R. (Robert), Wolk, A. (Alicja), Ziogas, A. (Argyrios), Michailidou, K. (Kyriaki), Chenevix-Trench, G. (Georgia), Bachelot, T. (Thomas), and Schmidt, M. K. (Marjanka K.)
Abstract: Breast cancer metastasis accounts for most of the deaths from breast cancer. Identification of germline variants associated with survival in aggressive types of breast cancer may inform understanding of breast cancer progression and assist treatment. In this analysis, we studied the associations between germline variants and breast cancer survival for patients with distant metastases at primary breast cancer diagnosis. We used data from the Breast Cancer Association Consortium (BCAC) including 1062 women of European ancestry with metastatic breast cancer, 606 of whom died of breast cancer. We identified two germline variants on chromosome 1, rs138569520 and rs146023652, significantly associated with breast cancer-specific survival (P = 3.19 × 10−8 and 4.42 × 10−8). In silico analysis suggested a potential regulatory effect of the variants on the nearby target genes SDE2 and H3F3A. However, the variants showed no evidence of association in a smaller replication dataset. The validation dataset was obtained from the SNPs to Risk of Metastasis (StoRM) study and included 293 patients with metastatic primary breast cancer at diagnosis. Ultimately, larger replication studies are needed to confirm the identified associations.
Published: 2021

21. 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

22. 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

23. Mutant K-Ras increases GSK-3β gene expression via an ETS-p300 transcriptional complex in pancreatic cancer

Author: Zhang, J-S, Koenig, A, Harrison, A, Ugolkov, A V, Fernandez-Zapico, M E, Couch, F J, and Billadeau, D D
Published: 2011
Full Text: View/download PDF

24. Centrosome-related genes, genetic variation, and risk of breast cancer

Author: Olson, J. E., Wang, X., Pankratz, V. S., Fredericksen, Z. S., Vachon, C. M., Vierkant, R. A., Cerhan, J. R., and Couch, F. J.
Published: 2011
Full Text: View/download PDF

25. Variation in genes required for normal mitosis and risk of breast cancer

Author: Olson, J. E., Wang, X., Goode, E. L., Pankratz, V. S., Fredericksen, Z. S., Vierkant, R. A., Pharoah, P. D. P., Cerhan, J. R., and Couch, F. J.
Published: 2010
Full Text: View/download PDF

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

Author: Zhang, H. (Haoyu), Ahearn, T. U. (Thomas U.), Lecarpentier, J. (Julie), Barnes, D. (Daniel), Beesley, J. (Jonathan), Qi, G. (Guanghao), Hang, X. (Xia), O'Mara, T. A. (Tracy A.), Zhao, N. (Ni), Bolla, M. K. (Manjeet K.), Dunning, A. M. (Alison M.), Dennis, J. (Joe), Wang, Q. (Qin), Abu Ful, Z. (Zumuruda), Aittomaki, K. (Kristiina), Andrulis, I. L. (Irene L.), Anton-Culver, H. (Hoda), Arndt, V. (Volker), Aronson, K. J. (Kristan J.), Arun, B. K. (Banu K.), Auer, P. L. (Paul L.), Azzollini, J. (Jacopo), Barrowdale, D. (Daniel), Becher, H. (Heiko), Beckmann, M. W. (Matthias W.), Behrens, S. (Sabine), Benitez, J. (Javier), Bermisheva, M. (Marina), Bialkowska, K. (Katarzyna), Blanco, A. (Ana), Blomqvist, C. (Carl), Bogdanova, N. V. (Natalia, V), Bojesen, S. E. (Stig E.), Bonanni, B. (Bernardo), Bondavalli, D. (Davide), Borg, A. (Ake), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Briceno, I. (Ignacio), Broeks, A. (Annegien), Brucker, S. Y. (Sara Y.), Bruening, T. (Thomas), Burwinkel, B. (Barbara), Buys, S. S. (Saundra S.), Byers, H. (Helen), Caldes, T. (Trinidad), Caligo, M. A. (Maria A.), Calvello, M. (Mariarosaria), Campa, D. (Daniele), Castelao, J. E. (Jose E.), Chang-Claude, J. (Jenny), Chanock, S. J. (Stephen J.), Christiaens, M. (Melissa), Christiansen, H. (Hans), Chung, W. K. (Wendy K.), Claes, K. B. (Kathleen B. M.), Clarke, C. L. (Christine L.), Cornelissen, S. (Sten), Couch, F. J. (Fergus J.), Cox, A. (Angela), Cross, S. S. (Simon S.), Czene, K. (Kamila), Daly, M. B. (Mary B.), Devilee, P. (Peter), Diez, O. (Orland), Domchek, S. M. (Susan M.), Doerk, T. (Thilo), Dwek, M. (Miriam), Eccles, D. M. (Diana M.), Ekici, A. B. (Arif B.), Evans, D. G. (D. Gareth), Fasching, P. A. (Peter A.), Figueroa, J. (Jonine), Foretova, L. (Lenka), Fostira, F. (Florentia), Friedman, E. (Eitan), Frost, D. (Debra), Gago-Dominguez, M. (Manuela), Gapstur, S. M. (Susan M.), Garber, J. (Judy), Garcia-Saenz, J. A. (Jose A.), Gaudet, M. M. (Mia M.), Gayther, S. A. (Simon A.), Giles, G. G. (Graham G.), Godwin, A. K. (Andrew K.), Goldberg, M. S. (Mark S.), Goldgar, D. E. (David E.), Gonzalez-Neira, A. (Anna), Greene, M. H. (Mark H.), Gronwald, J. (Jacek), Guenel, P. (Pascal), Haeberle, L. (Lothar), Hahnen, E. (Eric), Haiman, C. A. (Christopher A.), Hake, C. R. (Christopher R.), Hall, P. (Per), Hamann, U. (Ute), Harkness, E. F. (Elaine F.), Heemskerk-Gerritsen, B. A. (Bernadette A. M.), Hillemanns, P. (Peter), Hogervorst, F. B. (Frans B. L.), Holleczek, B. (Bernd), Hollestelle, A. (Antoinette), Hooning, M. J. (Maartje J.), Hoover, R. N. (Robert N.), Hopper, J. L. (John L.), Howell, A. (Anthony), Huebner, H. (Hanna), Hulick, P. J. (Peter J.), Imyanitov, E. N. (Evgeny N.), Isaacs, C. (Claudine), Izatt, L. (Louise), Jager, A. (Agnes), Jakimovska, M. (Milena), Jakubowska, A. (Anna), James, P. (Paul), Janavicius, R. (Ramunas), Janni, W. (Wolfgang), John, E. M. (Esther M.), Jones, M. E. (Michael E.), Jung, A. (Audrey), Kaaks, R. (Rudolf), Kapoor, P. M. (Pooja Middha), Karlan, B. Y. (Beth Y.), Keeman, R. (Renske), Khan, S. (Sofia), Khusnutdinova, E. (Elza), Kitahara, C. M. (Cari M.), Ko, Y.-D. (Yon-Dschun), Konstantopoulou, I. (Irene), Koppert, L. B. (Linetta B.), Koutros, S. (Stella), Kristensen, V. N. (Vessela N.), Laenkholm, A.-V. (Anne-Vibeke), Lambrechts, D. (Diether), Larsson, S. C. (Susanna C.), Laurent-Puig, P. (Pierre), Lazaro, C. (Conxi), Lazarova, E. (Emilija), Lejbkowicz, F. (Flavio), Leslie, G. (Goska), Lesueur, F. (Fabienne), Lindblom, A. (Annika), Lissowska, J. (Jolanta), Lo, W.-Y. (Wing-Yee), Loud, J. T. (Jennifer T.), Lubinski, J. (Jan), Lukomska, A. (Alicja), Maclnnis, R. J. (Robert J.), Mannermaa, A. (Arto), Manoochehri, M. (Mehdi), Manoukian, S. (Siranoush), Margolin, S. (Sara), Martinez, M. E. (Maria Elena), Matricardi, L. (Laura), McGuffog, L. (Lesley), McLean, C. (Catriona), Mebirouk, N. (Noura), Meindl, A. (Alfons), Menon, U. (Usha), Miller, A. (Austin), Mingazheva, E. (Elvira), Montagna, M. (Marco), Mulligan, A. M. (Anna Marie), Mulot, C. (Claire), Muranen, T. A. (Taru A.), Nathanson, K. L. (Katherine L.), Neuhausen, S. L. (Susan L.), Nevanlinna, H. (Heli), Neven, P. (Patrick), Newman, W. G. (William G.), Nielsens, F. C. (Finn C.), Nikitina-Zake, L. (Liene), Nodora, J. (Jesse), Offit, K. (Kenneth), Olah, E. (Edith), Olopade, O. I. (Olufunmilayo, I), Olsson, H. (Hakan), Orr, N. (Nick), Papi, L. (Laura), Papp, J. (Janos), Park-Simon, T.-W. (Tjoung-Won), Parsons, M. T. (Michael T.), Peissel, B. (Bernard), Peixoto, A. (Ana), Peshkin, B. (Beth), Peterlongo, P. (Paolo), Peto, J. (Julian), Phillips, K.-A. (Kelly-Anne), Piedmonte, M. (Marion), Plaseska-Karanfilska, D. (Dijana), Prajzendanc, K. (Karolina), Prentice, R. (Ross), Prokofyeva, D. (Darya), Rack, B. (Brigitte), Radice, P. (Paolo), Ramus, S. J. (Susan J.), Rantala, J. (Johanna), Rashid, M. U. (Muhammad U.), Rennert, G. (Gad), Rennert, H. S. (Hedy S.), Risch, H. A. (Harvey A.), Romero, A. (Atocha), Rookus, M. A. (Matti A.), Ruebner, M. (Matthias), Ruediger, T. (Thomas), Saloustros, E. (Emmanouil), Sampson, S. (Sarah), Sandler, D. P. (Dale P.), Sawyer, E. J. (Elinor J.), Scheuner, M. T. (Maren T.), Schmutzler, R. K. (Rita K.), Schneeweiss, A. (Andreas), Schoemaker, M. J. (Minouk J.), Schoettker, B. (Ben), Schuermann, P. (Peter), Senter, L. (Leigha), Sharma, P. (Priyanka), Sherman, M. E. (Mark E.), Shu, X.-O. (Xiao-Ou), Singer, C. F. (Christian F.), Smichkoska, S. (Snezhana), Soucy, P. (Penny), Southey, M. C. (Melissa C.), Spinelli, J. J. (John J.), Stone, J. (Jennifer), Stoppa-Lyonnet, D. (Dominique), Swerdlow, A. J. (Anthony J.), Szabo, C. I. (Csilla, I), Tamimi, R. M. (Rulla M.), Tapper, W. J. (William J.), Taylor, J. A. (Jack A.), Teixeira, M. R. (Manuel R.), Terry, M. (MaryBeth), Thomassen, M. (Mads), Thull, D. L. (Darcy L.), Tischkowitz, M. (Marc), Toland, A. E. (Amanda E.), Tollenaar, R. A. (Rob A. E. M.), Tomlinson, I. (Ian), Torres, D. (Diana), Troester, M. A. (Melissa A.), Truong, T. (Therese), Tung, N. (Nadine), Untch, M. (Michael), Vachon, C. M. (Celine M.), van den Ouweland, A. M. (Ans M. W.), van der Kolk, L. E. (Lizet E.), van Veen, E. M. (Elke M.), vanRensburg, E. J. (Elizabeth J.), Vega, A. (Ana), Wappenschmidt, B. (Barbara), Weinberg, C. R. (Clarice R.), Weitzel, J. N. (Jeffrey N.), Wildiers, H. (Hans), Winqvist, R. (Robert), Wolk, A. (Alicja), Yang, X. R. (Xiaohong R.), Yannoukakos, D. (Drakoulis), Zheng, W. (Wei), Zorn, K. K. (Kristin K.), Milne, R. L. (Roger L.), Kraft, P. (Peter), Simard, J. (Jacques), Pharoah, P. D. (Paul D. P.), Michailidou, K. (Kyriaki), Antoniou, A. C. (Antonis C.), Schmidt, M. K. (Marjanka K.), Chenevix-Trench, G. (Georgia), Easton, D. F. (Douglas F.), Chatterjee, N. (Nilanjan), and Garcia-Closas, M. (Montserrat)
Abstract: Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype. 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

27. A multi-centre international quality control study comparing mRNA splicing assay protocols and reporting practices from the ENIGMA consortium

Author: Whiley P, Walker LC, De LA Hoya M, Wappenschmidt B, Becker A, Blanco A, Blok MJ, Caligo MA, Chatfield C, Couch F, Diez O, Fachal L, Guidugli L, Enríquez S, Hansen T, Houdayer C, Imrie S, Lafferty A, Lázaro C, Menéndez M, Montagna M, Montalbán G, Santamariña M, Pederson I, Southey M, Tancredi M, Tenès A, Thomassen M, Van Overeem Vega A, Spurdle AB, and Brown MA
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282, Genetics, QH426-470
Published: 2012
Full Text: View/download PDF

28. Cancer risks associated with germline PALB2 pathogenic variants: An international study of 524 families.

Author: Hake C., Redman J., Kleibl Z., Kleiblova P., Konstantopoulou I., Kvist A., Laduca H., Lee A.S.G., Lesueur F., Maher E.R., Mannermaa A., Manoukian S., McFarland R., McKinnon W., Meindl A., Metcalfe K., Taib N.A.M., Moilanen J., Nathanson K.L., Neuhausen S., Ng P.S., Nguyen-Dumont T., Nielsen S.M., Obermair F., Offit K., Olopade O.I., Ottini L., Penkert J., Pylkas K., Radice P., Ramus S.J., Rudaitis V., Side L., Silva-Smith R., Silvestri V., Skytte A.-B., Slavin T., Soukupova J., Tondini C., Trainer A.H., Unzeitig G., Usha L., Van Overeem Hansen T., Whitworth J., Wood M., Yip C.H., Yoon S.-Y., Yussuf A., Zogopoulos G., Goldgar D., Hopper J.L., Chenevix-Trench G., Pharoah P., George S.H.L., Balmana J., Houdayer C., James P., El-Haffaf Z., Ehrencrona H., Janatova M., Peterlongo P., Nevanlinna H., Schmutzler R., Teo S.-H., Robson M., Pal T., Couch F., Weitzel J.N., Elliott A., Southey M., Winqvist R., Easton D.F., Foulkes W.D., Antoniou A.C., Tischkowitz M., Yang X., Leslie G., Doroszuk A., Schneider S., Allen J., Decker B., Dunning A.M., Scarth J., Plaskocinska I., Luccarini C., Shah M., Pooley K., Dorling L., Leei A., Adank M.A., Adlard J., Aittomaki K., Andrulis I.L., Ang P., Barwell J., Bernstein J.L., Bobolis K., Borg A., Blomqvist C., Claes K.B.M., Concannon P., Cuggia A., Culver J.O., Damiola F., De Pauw A., Diez O., Dolinsky J.S., Domchek S.M., Engel C., Evans D.G., Fostira F., Garber J., Golmard L., Goode E.L., Gruber S.B., Hahnen E., Heikkinen T., Hurley J.E., Janavicius R., Hake C., Redman J., Kleibl Z., Kleiblova P., Konstantopoulou I., Kvist A., Laduca H., Lee A.S.G., Lesueur F., Maher E.R., Mannermaa A., Manoukian S., McFarland R., McKinnon W., Meindl A., Metcalfe K., Taib N.A.M., Moilanen J., Nathanson K.L., Neuhausen S., Ng P.S., Nguyen-Dumont T., Nielsen S.M., Obermair F., Offit K., Olopade O.I., Ottini L., Penkert J., Pylkas K., Radice P., Ramus S.J., Rudaitis V., Side L., Silva-Smith R., Silvestri V., Skytte A.-B., Slavin T., Soukupova J., Tondini C., Trainer A.H., Unzeitig G., Usha L., Van Overeem Hansen T., Whitworth J., Wood M., Yip C.H., Yoon S.-Y., Yussuf A., Zogopoulos G., Goldgar D., Hopper J.L., Chenevix-Trench G., Pharoah P., George S.H.L., Balmana J., Houdayer C., James P., El-Haffaf Z., Ehrencrona H., Janatova M., Peterlongo P., Nevanlinna H., Schmutzler R., Teo S.-H., Robson M., Pal T., Couch F., Weitzel J.N., Elliott A., Southey M., Winqvist R., Easton D.F., Foulkes W.D., Antoniou A.C., Tischkowitz M., Yang X., Leslie G., Doroszuk A., Schneider S., Allen J., Decker B., Dunning A.M., Scarth J., Plaskocinska I., Luccarini C., Shah M., Pooley K., Dorling L., Leei A., Adank M.A., Adlard J., Aittomaki K., Andrulis I.L., Ang P., Barwell J., Bernstein J.L., Bobolis K., Borg A., Blomqvist C., Claes K.B.M., Concannon P., Cuggia A., Culver J.O., Damiola F., De Pauw A., Diez O., Dolinsky J.S., Domchek S.M., Engel C., Evans D.G., Fostira F., Garber J., Golmard L., Goode E.L., Gruber S.B., Hahnen E., Heikkinen T., Hurley J.E., and Janavicius R.
Abstract: PURPOSE To estimate age-specific relative and absolute cancer risks of breast cancer and to estimate risks of ovarian, pancreatic, male breast, prostate, and colorectal cancers associated with germline PALB2 pathogenic variants (PVs) because these risks have not been extensively characterized. METHODS We analyzed data from 524 families with PALB2 PVs from 21 countries. Complex segregation analysis was used to estimate relative risks (RRs; relative to country-specific population incidences) and absolute risks of cancers. The models allowed for residual familial aggregation of breast and ovarian cancer and were adjusted for the family-specific ascertainment schemes. RESULTS We found associations between PALB2 PVs and risk of female breast cancer (RR, 7.18; 95% CI, 5.82 to 8.85; P = 6.5 x 10-76), ovarian cancer (RR, 2.91; 95% CI, 1.40 to 6.04; P = 4.1 x 10-3), pancreatic cancer (RR, 2.37; 95% CI, 1.24 to 4.50; P = 8.7 x 10-3), and male breast cancer (RR, 7.34; 95% CI, 1.28 to 42.18; P = 2.6 3 1022). There was no evidence for increased risks of prostate or colorectal cancer. The breast cancer RRs declined with age (P for trend = 2.0 x 10-3). After adjusting for family ascertainment, breast cancer risk estimates on the basis of multiple case families were similar to the estimates from families ascertained through population-based studies (P for difference = .41). On the basis of the combined data, the estimated risks to age 80 years were 53% (95% CI, 44% to 63%) for female breast cancer, 5% (95% CI, 2% to 10%) for ovarian cancer, 2%-3% (95% CI females, 1% to 4%; 95% CI males, 2% to 5%) for pancreatic cancer, and 1% (95% CI, 0.2% to 5%) for male breast cancer. CONCLUSION These results confirm PALB2 as a major breast cancer susceptibility gene and establish substantial associations between germline PALB2 PVs and ovarian, pancreatic, and male breast cancers. These findings will facilitate incorporation of PALB2 into risk prediction models and optimize the clinical cancer ri
Published: 2020

29. Cancer Risks Associated With Germline PALB2 Pathogenic Variants: An International Study of 524 Families

Author: Yang, X, Leslie, G, Doroszuk, A, Schneider, S, Allen, J, Decker, B, Dunning, AM, Redman, J, Scarth, J, Plaskocinska, I, Luccarini, C, Shah, M, Pooley, K, Dorling, L, Lee, A, Adank, MA, Adlard, J, Aittomaki, K, Andrulis, IL, Ang, P, Barwell, J, Bernstein, JL, Bobolis, K, Borg, A, Blomqvist, C, Claes, KBM, Concannon, P, Cuggia, A, Culver, JO, Damiola, F, de Pauw, A, Diez, O, Dolinsky, JS, Domchek, SM, Engel, C, Evans, DG, Fostira, F, Garber, J, Golmard, L, Goode, EL, Gruber, SB, Hahnen, E, Hake, C, Heikkinen, T, Hurley, JE, Janavicius, R, Kleibl, Z, Kleiblova, P, Konstantopoulou, I, Kvist, A, Laduca, H, Lee, ASG, Lesueur, F, Maher, ER, Mannermaa, A, Manoukian, S, McFarland, R, McKinnon, W, Meindl, A, Metcalfe, K, Taib, NAM, Moilanen, J, Nathanson, KL, Neuhausen, S, Ng, PS, Nguyen-Dumont, T, Nielsen, SM, Obermair, F, Offit, K, Olopade, O, Ottini, L, Penkert, J, Pylkas, K, Radice, P, Ramus, SJ, Rudaitis, V, Side, L, Silva-Smith, R, Silvestri, V, Skytte, A-B, Slavin, T, Soukupova, J, Tondini, C, Trainer, AH, Unzeitig, G, Usha, L, Hansen, TVO, Whitworth, J, Wood, M, Yip, CH, Yoon, S-Y, Yussuf, A, Zogopoulos, G, Goldgar, D, Hopper, JL, Chenevix-Trench, G, Pharoah, P, George, SHL, Balmana, J, Houdayer, C, James, P, El-Haffaf, Z, Ehrencrona, H, Janatova, M, Peterlongo, P, Nevanlinna, H, Schmutzler, R, Teo, S-H, Robson, M, Pal, T, Couch, F, Weitzel, JN, Elliott, A, Southey, M, Winqvist, R, Easton, DF, Foulkes, WD, Antoniou, AC, Tischkowitz, M, Yang, X, Leslie, G, Doroszuk, A, Schneider, S, Allen, J, Decker, B, Dunning, AM, Redman, J, Scarth, J, Plaskocinska, I, Luccarini, C, Shah, M, Pooley, K, Dorling, L, Lee, A, Adank, MA, Adlard, J, Aittomaki, K, Andrulis, IL, Ang, P, Barwell, J, Bernstein, JL, Bobolis, K, Borg, A, Blomqvist, C, Claes, KBM, Concannon, P, Cuggia, A, Culver, JO, Damiola, F, de Pauw, A, Diez, O, Dolinsky, JS, Domchek, SM, Engel, C, Evans, DG, Fostira, F, Garber, J, Golmard, L, Goode, EL, Gruber, SB, Hahnen, E, Hake, C, Heikkinen, T, Hurley, JE, Janavicius, R, Kleibl, Z, Kleiblova, P, Konstantopoulou, I, Kvist, A, Laduca, H, Lee, ASG, Lesueur, F, Maher, ER, Mannermaa, A, Manoukian, S, McFarland, R, McKinnon, W, Meindl, A, Metcalfe, K, Taib, NAM, Moilanen, J, Nathanson, KL, Neuhausen, S, Ng, PS, Nguyen-Dumont, T, Nielsen, SM, Obermair, F, Offit, K, Olopade, O, Ottini, L, Penkert, J, Pylkas, K, Radice, P, Ramus, SJ, Rudaitis, V, Side, L, Silva-Smith, R, Silvestri, V, Skytte, A-B, Slavin, T, Soukupova, J, Tondini, C, Trainer, AH, Unzeitig, G, Usha, L, Hansen, TVO, Whitworth, J, Wood, M, Yip, CH, Yoon, S-Y, Yussuf, A, Zogopoulos, G, Goldgar, D, Hopper, JL, Chenevix-Trench, G, Pharoah, P, George, SHL, Balmana, J, Houdayer, C, James, P, El-Haffaf, Z, Ehrencrona, H, Janatova, M, Peterlongo, P, Nevanlinna, H, Schmutzler, R, Teo, S-H, Robson, M, Pal, T, Couch, F, Weitzel, JN, Elliott, A, Southey, M, Winqvist, R, Easton, DF, Foulkes, WD, Antoniou, AC, and Tischkowitz, M
Abstract: PURPOSE: To estimate age-specific relative and absolute cancer risks of breast cancer and to estimate risks of ovarian, pancreatic, male breast, prostate, and colorectal cancers associated with germline PALB2 pathogenic variants (PVs) because these risks have not been extensively characterized. METHODS: We analyzed data from 524 families with PALB2 PVs from 21 countries. Complex segregation analysis was used to estimate relative risks (RRs; relative to country-specific population incidences) and absolute risks of cancers. The models allowed for residual familial aggregation of breast and ovarian cancer and were adjusted for the family-specific ascertainment schemes. RESULTS: We found associations between PALB2 PVs and risk of female breast cancer (RR, 7.18; 95% CI, 5.82 to 8.85; P = 6.5 × 10-76), ovarian cancer (RR, 2.91; 95% CI, 1.40 to 6.04; P = 4.1 × 10-3), pancreatic cancer (RR, 2.37; 95% CI, 1.24 to 4.50; P = 8.7 × 10-3), and male breast cancer (RR, 7.34; 95% CI, 1.28 to 42.18; P = 2.6 × 10-2). There was no evidence for increased risks of prostate or colorectal cancer. The breast cancer RRs declined with age (P for trend = 2.0 × 10-3). After adjusting for family ascertainment, breast cancer risk estimates on the basis of multiple case families were similar to the estimates from families ascertained through population-based studies (P for difference = .41). On the basis of the combined data, the estimated risks to age 80 years were 53% (95% CI, 44% to 63%) for female breast cancer, 5% (95% CI, 2% to 10%) for ovarian cancer, 2%-3% (95% CI females, 1% to 4%; 95% CI males, 2% to 5%) for pancreatic cancer, and 1% (95% CI, 0.2% to 5%) for male breast cancer. CONCLUSION: These results confirm PALB2 as a major breast cancer susceptibility gene and establish substantial associations between germline PALB2 PVs and ovarian, pancreatic, and male breast cancers. These findings will facilitate incorporation of PALB2 into risk prediction models and optimize the clinical cance
Published: 2020

30. A network analysis to identify mediators of germline-driven differences in breast cancer prognosis

Author: Escala-Garcia, M. (Maria), Abraham, J. (Jean), Andrulis, I. L. (Irene L.), Anton-Culver, H. (Hoda), Arndt, V. (Volker), Ashworth, A. (Alan), Auer, P. L. (Paul L.), Auvinen, P. (Paivi), Beckmann, M. W. (Matthias W.), Beesley, J. (Jonathan), Behrens, S. (Sabine), Benitez, J. (Javier), Bermisheva, M. (Marina), Blomqvist, C. (Carl), Blot, W. (William), Bogdanova, N. V. (Natalia V.), Bojesen, S. E. (Stig E.), Bolla, M. K. (Manjeet K.), Borresen-Dale, A.-L. (Anne-Lise), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Brucker, S. Y. (Sara Y.), Burwinkel, B. (Barbara), Caldas, C. (Carlos), Canzian, F. (Federico), Chang-Claude, J. (Jenny), Chanock, S. J. (Stephen J.), Chin, S.-F. (Suet-Feung), Clarke, C. L. (Christine L.), Couch, F. J. (Fergus J.), Cox, A. (Angela), Cross, S. S. (Simon S.), Czene, K. (Kamila), Daly, M. B. (Mary B.), Dennis, J. (Joe), Devilee, P. (Peter), Dunn, J. A. (Janet A.), Dunning, A. M. (Alison M.), Dwek, M. (Miriam), Earl, H. M. (Helena M.), Eccles, D. M. (Diana M.), Eliassen, A. H. (A. Heather), Ellberg, C. (Carolina), Evans, D. G. (D. Gareth), Fasching, P. A. (Peter A.), Figueroa, J. (Jonine), Flyger, H. (Henrik), Gago-Dominguez, M. (Manuela), Gapstur, S. M. (Susan M.), Garcia-Closas, M. (Montserrat), Garcia-Saenz, J. A. (Jose A.), Gaudet, M. M. (Mia M.), George, A. (Angela), Giles, G. G. (Graham G.), Goldgar, D. E. (David E.), Gonzalez-Neira, A. (Anna), Grip, M. (Mervi), Guenel, P. (Pascal), Guo, Q. (Qi), Haiman, C. A. (Christopher A.), Hakansson, N. (Niclas), Hamann, U. (Ute), Harrington, P. A. (Patricia A.), Hiller, L. (Louise), Hooning, M. J. (Maartje J.), Hopper, J. L. (John L.), Howell, A. (Anthony), Huang, C.-S. (Chiun-Sheng), Huang, G. (Guanmengqian), Hunter, D. J. (David J.), Jakubowska, A. (Anna), John, E. M. (Esther M.), Kaaks, R. (Rudolf), Kapoor, P. M. (Pooja Middha), Keeman, R. (Renske), Kitahara, C. M. (Cari M.), Koppert, L. B. (Linetta B.), Kraft, P. (Peter), Kristensen, V. N. (Vessela N.), Lambrechts, D. (Diether), Le Marchand, L. (Loic), Lejbkowicz, F. (Flavio), Lindblom, A. (Annika), Lubinski, J. (Jan), Mannermaa, A. (Arto), Manoochehri, M. (Mehdi), Manoukian, S. (Siranoush), Margolin, S. (Sara), Martinez, M. E. (Maria Elena), Maurer, T. (Tabea), Mavroudis, D. (Dimitrios), Meindl, A. (Alfons), Milne, R. L. (Roger L.), Mulligan, A. M. (Anna Marie), Neuhausen, S. L. (Susan L.), Nevanlinna, H. (Heli), Newman, W. G. (William G.), Olshan, A. F. (Andrew F.), Olson, J. E. (Janet E.), Olsson, H. (Hakan), Orr, N. (Nick), Peterlongo, P. (Paolo), Petridis, C. (Christos), Prentice, R. L. (Ross L.), Presneau, N. (Nadege), Punie, K. (Kevin), Ramachandran, D. (Dhanya), Rennert, G. (Gad), Romero, A. (Atocha), Sachchithananthan, M. (Mythily), Saloustros, E. (Emmanouil), Sawyer, E. J. (Elinor J.), Schmutzler, R. K. (Rita K.), Schwentner, L. (Lukas), Scott, C. (Christopher), Simard, J. (Jacques), Sohn, C. (Christof), Southey, M. C. (Melissa C.), Swerdlow, A. J. (Anthony J.), Tamimi, R. M. (Rulla M.), Tapper, W. J. (William J.), Teixeira, M. R. (Manuel R.), Terry, M. B. (Mary Beth), Thorne, H. (Heather), Tollenaar, R. A. (Rob A. E. M.), Tomlinson, I. (Ian), Troester, M. A. (Melissa A.), Truong, T. (Therese), Turnbull, C. (Clare), Vachon, C. M. (Celine M.), van der Kolk, L. E. (Lizet E.), Wang, Q. (Qin), Winqvist, R. (Robert), Wolk, A. (Alicja), Yang, X. R. (Xiaohong R.), Ziogas, A. (Argyrios), Pharoah, P. D. (Paul D. P.), Hall, P. (Per), Wessels, L. F. (Lodewyk F. A.), Chenevix-Trench, G. (Georgia), Bader, G. D. (Gary D.), Doerk, T. (Thilo), Easton, D. F. (Douglas F.), Canisius, S. (Sander), Schmidt, M. K. (Marjanka K.), Escala-Garcia, M. (Maria), Abraham, J. (Jean), Andrulis, I. L. (Irene L.), Anton-Culver, H. (Hoda), Arndt, V. (Volker), Ashworth, A. (Alan), Auer, P. L. (Paul L.), Auvinen, P. (Paivi), Beckmann, M. W. (Matthias W.), Beesley, J. (Jonathan), Behrens, S. (Sabine), Benitez, J. (Javier), Bermisheva, M. (Marina), Blomqvist, C. (Carl), Blot, W. (William), Bogdanova, N. V. (Natalia V.), Bojesen, S. E. (Stig E.), Bolla, M. K. (Manjeet K.), Borresen-Dale, A.-L. (Anne-Lise), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Brucker, S. Y. (Sara Y.), Burwinkel, B. (Barbara), Caldas, C. (Carlos), Canzian, F. (Federico), Chang-Claude, J. (Jenny), Chanock, S. J. (Stephen J.), Chin, S.-F. (Suet-Feung), Clarke, C. L. (Christine L.), Couch, F. J. (Fergus J.), Cox, A. (Angela), Cross, S. S. (Simon S.), Czene, K. (Kamila), Daly, M. B. (Mary B.), Dennis, J. (Joe), Devilee, P. (Peter), Dunn, J. A. (Janet A.), Dunning, A. M. (Alison M.), Dwek, M. (Miriam), Earl, H. M. (Helena M.), Eccles, D. M. (Diana M.), Eliassen, A. H. (A. Heather), Ellberg, C. (Carolina), Evans, D. G. (D. Gareth), Fasching, P. A. (Peter A.), Figueroa, J. (Jonine), Flyger, H. (Henrik), Gago-Dominguez, M. (Manuela), Gapstur, S. M. (Susan M.), Garcia-Closas, M. (Montserrat), Garcia-Saenz, J. A. (Jose A.), Gaudet, M. M. (Mia M.), George, A. (Angela), Giles, G. G. (Graham G.), Goldgar, D. E. (David E.), Gonzalez-Neira, A. (Anna), Grip, M. (Mervi), Guenel, P. (Pascal), Guo, Q. (Qi), Haiman, C. A. (Christopher A.), Hakansson, N. (Niclas), Hamann, U. (Ute), Harrington, P. A. (Patricia A.), Hiller, L. (Louise), Hooning, M. J. (Maartje J.), Hopper, J. L. (John L.), Howell, A. (Anthony), Huang, C.-S. (Chiun-Sheng), Huang, G. (Guanmengqian), Hunter, D. J. (David J.), Jakubowska, A. (Anna), John, E. M. (Esther M.), Kaaks, R. (Rudolf), Kapoor, P. M. (Pooja Middha), Keeman, R. (Renske), Kitahara, C. M. (Cari M.), Koppert, L. B. (Linetta B.), Kraft, P. (Peter), Kristensen, V. N. (Vessela N.), Lambrechts, D. (Diether), Le Marchand, L. (Loic), Lejbkowicz, F. (Flavio), Lindblom, A. (Annika), Lubinski, J. (Jan), Mannermaa, A. (Arto), Manoochehri, M. (Mehdi), Manoukian, S. (Siranoush), Margolin, S. (Sara), Martinez, M. E. (Maria Elena), Maurer, T. (Tabea), Mavroudis, D. (Dimitrios), Meindl, A. (Alfons), Milne, R. L. (Roger L.), Mulligan, A. M. (Anna Marie), Neuhausen, S. L. (Susan L.), Nevanlinna, H. (Heli), Newman, W. G. (William G.), Olshan, A. F. (Andrew F.), Olson, J. E. (Janet E.), Olsson, H. (Hakan), Orr, N. (Nick), Peterlongo, P. (Paolo), Petridis, C. (Christos), Prentice, R. L. (Ross L.), Presneau, N. (Nadege), Punie, K. (Kevin), Ramachandran, D. (Dhanya), Rennert, G. (Gad), Romero, A. (Atocha), Sachchithananthan, M. (Mythily), Saloustros, E. (Emmanouil), Sawyer, E. J. (Elinor J.), Schmutzler, R. K. (Rita K.), Schwentner, L. (Lukas), Scott, C. (Christopher), Simard, J. (Jacques), Sohn, C. (Christof), Southey, M. C. (Melissa C.), Swerdlow, A. J. (Anthony J.), Tamimi, R. M. (Rulla M.), Tapper, W. J. (William J.), Teixeira, M. R. (Manuel R.), Terry, M. B. (Mary Beth), Thorne, H. (Heather), Tollenaar, R. A. (Rob A. E. M.), Tomlinson, I. (Ian), Troester, M. A. (Melissa A.), Truong, T. (Therese), Turnbull, C. (Clare), Vachon, C. M. (Celine M.), van der Kolk, L. E. (Lizet E.), Wang, Q. (Qin), Winqvist, R. (Robert), Wolk, A. (Alicja), Yang, X. R. (Xiaohong R.), Ziogas, A. (Argyrios), Pharoah, P. D. (Paul D. P.), Hall, P. (Per), Wessels, L. F. (Lodewyk F. A.), Chenevix-Trench, G. (Georgia), Bader, G. D. (Gary D.), Doerk, T. (Thilo), Easton, D. F. (Douglas F.), Canisius, S. (Sander), and Schmidt, M. K. (Marjanka K.)
Abstract: Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies ~7.3 million variants in 84,457 breast cancer patients in relation to breast cancer survival and confirms the results on 12,381 independent patients. Aggregating the prognostic effects of genetic variants across multiple genes, we identify four gene modules associated with survival in estrogen receptor (ER)-negative and one in ER-positive disease. The modules show biological enrichment for cancer-related processes such as G-alpha signaling, circadian clock, angiogenesis, and Rho-GTPases in apoptosis.
Published: 2020

31. Breastfeeding and the risk of epithelial ovarian cancer among women with a BRCA1 or BRCA2 mutation

Author: Kotsopoulos, J, Gronwald, J, Mccuaig, J, Karlan, B, Eisen, A, Tung, N, Bordeleau, L, Senter, L, Eng, C, Couch, F, Fruscio, R, Weitzel, J, Olopade, O, Singer, C, Pal, T, Foulkes, W, Neuhausen, S, Sun, P, Lubinski, J, Narod, S, Kotsopoulos, Joanne, Gronwald, Jacek, McCuaig, Jeanna M, Karlan, Beth Y, Eisen, Andrea, Tung, Nadine, Bordeleau, Louise, Senter, Leigha, Eng, Charis, Couch, Fergus, Fruscio, Robert, Weitzel, Jeffrey N, Olopade, Olufunmilayo, Singer, Christian F, Pal, Tuya, Foulkes, William D, Neuhausen, Susan L, Sun, Ping, Lubinski, Jan, Narod, Steven A, Kotsopoulos, J, Gronwald, J, Mccuaig, J, Karlan, B, Eisen, A, Tung, N, Bordeleau, L, Senter, L, Eng, C, Couch, F, Fruscio, R, Weitzel, J, Olopade, O, Singer, C, Pal, T, Foulkes, W, Neuhausen, S, Sun, P, Lubinski, J, Narod, S, Kotsopoulos, Joanne, Gronwald, Jacek, McCuaig, Jeanna M, Karlan, Beth Y, Eisen, Andrea, Tung, Nadine, Bordeleau, Louise, Senter, Leigha, Eng, Charis, Couch, Fergus, Fruscio, Robert, Weitzel, Jeffrey N, Olopade, Olufunmilayo, Singer, Christian F, Pal, Tuya, Foulkes, William D, Neuhausen, Susan L, Sun, Ping, Lubinski, Jan, and Narod, Steven A
Abstract: Objective: BRCA mutation carriers face a high lifetime risk of developing ovarian cancer. The strong inverse association between breastfeeding and the risk of ovarian cancer is established in the general population but is less well studied among women with a germline BRCA1 or BRCA2 mutation. Method: Thus, we conducted a matched case-control analysis to evaluate the association between breastfeeding history and the risk of developing ovarian cancer. After matching for year of birth, country of residence, BRCA gene and personal history of breast cancer, a total of 1650 cases and 2702 controls were included in the analysis. Conditional logistic regression was used to estimate the odds ratio (OR) and 95% confidence intervals (CI) associated with various breastfeeding exposures. Results: A history of ever-breastfeeding was associated with a 23% reduction in risk (OR = 0.77; 95%CI 0.66-0.90; P = 0.001). The protective effect increased with breastfeeding from one month to seven months after which the association was relatively stable. Compared to women who never breastfed, breastfeeding for seven or more months was associated with a 32% reduction in risk (OR = 0.68; 95%CI 0.57-0.81; P < 0.0001) and did not vary by BRCA gene or age at diagnosis. The combination of breastfeeding and oral contraceptive use was strongly protective (0.47; 95%CI 0.37-0.58; P < 0.0001). Conclusions: These findings support a protective effect of breastfeeding for at least seven months among women with a BRCA1 or BRCA2 mutation, that is independent of oral contraceptive use.
Published: 2020

32. Genome-wide association study of germline variants and breast cancer-specific mortality

Author: Escala-Garcia, M. (Maria), Guo, Q. (Qi), Doerk, T. (Thilo), Canisius, S. (Sander), Keeman, R. (Renske), Dennis, J. (Joe), Beesley, J. (Jonathan), Lecarpentier, J. (Julie), Bolla, M. K. (Manjeet K.), Wang, Q. (Qin), Abraham, J. (Jean), Andrulis, I. L. (Irene L.), Anton-Culver, H. (Hoda), Arndt, V. (Volker), Auer, P. L. (Paul L.), Beckmann, M. W. (Matthias W.), Behrens, S. (Sabine), Benitez, J. (Javier), Bermisheva, M. (Marina), Bernstein, L. (Leslie), Blomqvist, C. (Carl), Boeckx, B. (Bram), Bojesen, S. E. (Stig E.), Bonanni, B. (Bernardo), Borresen-Dale, A.-L. (Anne-Lise), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Brentnall, A. (Adam), Brinton, L. (Louise), Broberg, P. (Per), Brock, I. W. (Ian W.), Brucker, S. Y. (Sara Y.), Burwinkel, B. (Barbara), Caldas, C. (Carlos), Caldes, T. (Trinidad), Campa, D. (Daniele), Canzian, F. (Federico), Carracedo, A. (Angel), Carter, B. D. (Brian D.), Castelao, J. E. (Jose E.), Chang-Claude, J. (Jenny), Chanock, S. J. (Stephen J.), Chenevix-Trench, G. (Georgia), Cheng, T. D. (Ting-Yuan David), Chin, S.-F. (Suet-Feung), Clarke, C. L. (Christine L.), Cordina-Duverger, E. (Emilie), Couch, F. J. (Fergus J.), Cox, D. G. (David G.), Cox, A. (Angela), Cross, S. S. (Simon S.), Czene, K. (Kamila), Daly, M. B. (Mary B.), Devilee, P. (Peter), Dunn, J. A. (Janet A.), Dunning, A. M. (Alison M.), Durcan, L. (Lorraine), Dwek, M. (Miriam), Earl, H. M. (Helena M.), Ekici, A. B. (Arif B.), Eliassen, A. H. (A. Heather), Ellberg, C. (Carolina), Engel, C. (Christoph), Eriksson, M. (Mikael), Evans, D. G. (D. Gareth), Figueroa, J. (Jonine), Flesch-Janys, D. (Dieter), Flyger, H. (Henrik), Gabrielson, M. (Marike), Gago-Dominguez, M. (Manuela), Galle, E. (Eva), Gapstur, S. M. (Susan M.), Garcia-Closas, M. (Montserrat), Garcia-Saenz, J. A. (Jose A.), Gaudet, M. M. (Mia M.), George, A. (Angela), Georgoulias, V. (Vassilios), Giles, G. G. (Graham G.), Glendon, G. (Gord), Goldgar, D. E. (David E.), Gonzalez-Neira, A. (Anna), Alnaes, G. I. (Grethe I. Grenaker), Grip, M. (Mervi), Guenel, P. (Pascal), Haeberle, L. (Lothar), Hahnen, E. (Eric), Haiman, C. A. (Christopher A.), Hakansson, N. (Niclas), Hall, P. (Per), Hamann, U. (Ute), Hankinson, S. (Susan), Harkness, E. F. (Elaine F.), Harrington, P. A. (Patricia A.), Hart, S. N. (Steven N.), Hartikainen, J. M. (Jaana M.), Hein, A. (Alexander), Hillemanns, P. (Peter), Hiller, L. (Louise), Holleczek, B. (Bernd), Hollestelle, A. (Antoinette), Hooning, M. J. (Maartje J.), Hoover, R. N. (Robert N.), Hopper, J. L. (John L.), Howell, A. (Anthony), Huang, G. (Guanmengqian), Humphreys, K. (Keith), Hunter, D. J. (David J.), Janni, W. (Wolfgang), John, E. M. (Esther M.), Jones, M. E. (Michael E.), Jukkola-Vuorinen, A. (Arja), Jung, A. (Audrey), Kaaks, R. (Rudolf), Kabisch, M. (Maria), Kaczmarek, K. (Katarzyna), Kerin, M. J. (Michael J.), Khan, S. (Sofia), Khusnutdinova, E. (Elza), Kiiski, J. I. (Johanna, I), Kitahara, C. M. (Cari M.), Knight, J. A. (Julia A.), Ko, Y.-D. (Yon-Dschun), Koppert, L. B. (Linetta B.), Kosma, V.-M. (Veli-Matti), Kraft, P. (Peter), Kristensen, V. N. (Vessela N.), Kruger, U. (Ute), Kuehl, T. (Tabea), Lambrechts, D. (Diether), Le Marchand, L. (Loic), Lee, E. (Eunjung), Lejbkowicz, F. (Flavio), Li, L. (Lian), Lindblom, A. (Annika), Lindstrom, S. (Sara), Linet, M. (Martha), Lissowska, J. (Jolanta), Lo, W.-Y. (Wing-Yee), Loibl, S. (Sibylle), Lubinski, J. (Jan), Lux, M. P. (Michael P.), MacInnis, R. J. (Robert J.), Maierthaler, M. (Melanie), Maishman, T. (Tom), Makalic, E. (Enes), Mannermaa, A. (Arto), Manoochehri, M. (Mehdi), Manoukian, S. (Siranoush), Margolin, S. (Sara), Martinez, M. E. (Maria Elena), Mavroudis, D. (Dimitrios), McLean, C. (Catriona), Meindl, A. (Alfons), Middha, P. (Pooja), Miller, N. (Nicola), Milne, R. L. (Roger L.), Moreno, F. (Fernando), Mulligan, A. M. (Anna Marie), Mulot, C. (Claire), Nassir, R. (Rami), Neuhausen, S. L. (Susan L.), Newman, W. T. (William T.), Nielsen, S. F. (Sune F.), Nordestgaard, B. G. (Borge G.), Norman, A. (Aaron), Olsson, H. (Hakan), Orr, N. (Nick), Pankratz, V. S. (V. Shane), Park-Simon, T.-W. (Tjoung-Won), Perez, J. I. (Jose I. A.), Perez-Barrios, C. (Clara), Peterlongo, P. (Paolo), Petridis, C. (Christos), Pinchev, M. (Mila), Prajzendanc, K. (Karoliona), Prentice, R. (Ross), Presneau, N. (Nadege), Prokofieva, D. (Darya), Pylkas, K. (Katri), Rack, B. (Brigitte), Radice, P. (Paolo), Ramachandran, D. (Dhanya), Rennert, G. (Gadi), Rennert, H. S. (Hedy S.), Rhenius, V. (Valerie), Romero, A. (Atocha), Roylance, R. (Rebecca), Saloustros, E. (Emmanouil), Sawyer, E. J. (Elinor J.), Schmidt, D. F. (Daniel F.), Schmutzler, R. K. (Rita K.), Schneeweiss, A. (Andreas), Schoemaker, M. J. (Minouk J.), Schumacher, F. (Fredrick), Schwentner, L. (Lukas), Scott, R. J. (Rodney J.), Scott, C. (Christopher), Seynaeve, C. (Caroline), Shah, M. (Mitul), Simard, J. (Jacques), Smeets, A. (Ann), Sohn, C. (Christof), Southey, M. C. (Melissa C.), Swerdlow, A. J. (Anthony J.), Talhouk, A. (Aline), Tamimi, R. M. (Rulla M.), Tapper, W. J. (William J.), Teixeira, M. R. (Manuel R.), Tengstrom, M. (Maria), Terry, M. B. (Mary Beth), Thoene, K. (Kathrin), Tollenaar, R. A. (Rob A. E. M.), Tomlinson, I. (Ian), Torres, D. (Diana), Truong, T. (Therese), Turman, C. (Constance), Turnbull, C. (Clare), Ulmer, H.-U. (Hans-Ulrich), Untch, M. (Michael), Vachon, C. (Celine), van Asperen, C. J. (Christi J.), van den Ouweland, A. M. (Ans M. W.), van Veen, E. M. (Elke M.), Wendt, C. (Camilla), Whittemore, A. S. (Alice S.), Willett, W. (Walter), Winqvist, R. (Robert), Wolk, A. (Alicja), Yang, X. R. (Xiaohong R.), Zhang, Y. (Yan), Easton, D. F. (Douglas F.), Fasching, P. A. (Peter A.), Nevanlinna, H. (Heli), Eccles, D. M. (Diana M.), Pharoah, P. D. (Paul D. P.), and Schmidt, M. K. (Marjanka K.)
Abstract: Background: We examined the associations between germline variants and breast cancer mortality using a large meta-analysis of women of European ancestry. Methods: Meta-analyses included summary estimates based on Cox models of twelve datasets using ~10.4 million variants for 96,661 women with breast cancer and 7697 events (breast cancer-specific deaths). Oestrogen receptor (ER)-specific analyses were based on 64,171 ER-positive (4116) and 16,172 ER-negative (2125) patients. We evaluated the probability of a signal to be a true positive using the Bayesian false discovery probability (BFDP). Results: We did not find any variant associated with breast cancer-specific mortality at P < 5 × 10−8. For ER-positive disease, the most significantly associated variant was chr7:rs4717568 (BFDP = 7%, P = 1.28 × 10−7, hazard ratio [HR] = 0.88, 95% confidence interval [CI] = 0.84–0.92); the closest gene is AUTS2. For ER-negative disease, the most significant variant was chr7:rs67918676 (BFDP = 11%, P = 1.38 × 10−7, HR = 1.27, 95% CI = 1.16–1.39); located within a long intergenic non-coding RNA gene (AC004009.3), close to the HOXA gene cluster. Conclusions: We uncovered germline variants on chromosome 7 at BFDP
Published: 2019

33. Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes

Author: Mavaddat, N., Michailidou, K., Dennis, J., Lush, M., Fachal, L., Lee, A., Tyrer, J. P., Chen, T. H., Wang, Q., Bolla, M. K., Yang, X., Adank, M. A., Ahearn, T., Aittomaki, K., Allen, J., Andrulis, I. L., Anton-Culver, H., Antonenkova, N. N., Arndt, V., Aronson, K. J., Auer, P. L., Auvinen, P., Barrdahl, M., Beane Freeman, L. E., Beckmann, M. W., Behrens, S., Benitez, J., Bermisheva, M., Bernstein, L., Blomqvist, C., Bogdanova, N. V., Bojesen, S. E., Bonanni, B., Borresen-Dale, A. L., Brauch, H., Bremer, M., Brenner, H., Brentnall, A., Brock, I. W., Brooks-Wilson, A., Brucker, S. Y., Bruning, T., Burwinkel, B., Campa, D., Carter, B. D., Castelao Fernández, José Esteban, Chanock, S. J., Chlebowski, R., Christiansen, H., Clarke, C. L., Collee, J. M., Cordina-Duverger, E., Cornelissen, S., Couch, F. J., Cox, A., Cross, S. S., Czene, K., Daly, M. B., Devilee, P., Dork, T., Dos-Santos-Silva, I., Dumont, M., Durcan, L., Dwek, M., Eccles, D. M., Ekici, A. B., Eliassen, A. H., Ellberg, C., Engel, C., Eriksson, M., Evans, D. G., Fasching, P. A., Figueroa, J., Fletcher, O., Flyger, H., Forsti, A., Fritschi, L., Gabrielson, M., Gago Dominguez, Manuela, Gapstur, S. M., Garcia-Saenz, J. A., Gaudet, M. M., Georgoulias, V., Giles, G. G., Gilyazova, I. R., Glendon, G., Goldberg, M. S., Goldgar, D. E., Gonzalez-Neira, A., Grenaker Alnaes, G. I., Grip, M., Gronwald, J., Grundy, A., Guenel, P., Haeberle, L., Hahnen, E., Haiman, C. A., Hakansson, N., Hamann, U., Hankinson, S. E., Muñoz Garzón, Victor, and others
Subjects: Adult, Aged, 80 and over, Multifactorial Inheritance, anciano, humanos, Age Factors, Reproducibility of Results, Breast Neoplasms, neoplasias de la mama, predisposición genética a la enfermedad, Middle Aged, adulto, Risk Assessment, Polymorphism, Single Nucleotide, herencia multifactorial, reproducibilidad de resultados, Receptors, Estrogen, evaluación de riesgos, Humans, Genetic Predisposition to Disease, anamnesis, Female, Medical History Taking, mediana edad, Aged
Abstract: Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets. Samples were genotyped using genome-wide arrays, and single-nucleotide polymorphisms (SNPs) were selected by stepwise regression or lasso penalized regression. The best performing PRSs were validated in an independent test set comprising 11,428 case subjects and 18,323 control subjects from 10 prospective studies and 190,040 women from UK Biobank (3,215 incident breast cancers). For the best PRSs (313 SNPs), the odds ratio for overall disease per 1 standard deviation in ten prospective studies was 1.61 (95%CI: 1.57-1.65) with area under receiver-operator curve (AUC) = 0.630 (95%CI: 0.628-0.651). The lifetime risk of overall breast cancer in the top centile of the PRSs was 32.6%. Compared with women in the middle quintile, those in the highest 1% of risk had 4.37- and 2.78-fold risks, and those in the lowest 1% of risk had 0.16- and 0.27-fold risks, of developing ER-positive and ER-negative disease, respectively. Goodness-of-fit tests indicated that this PRS was well calibrated and predicts disease risk accurately in the tails of the distribution. This PRS is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs.
Published: 2019

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

Author: Figlioli, G., Bogliolo, M., Catucci, I., Caleca, L., Lasheras, S. V., Pujol, R., Kiiski, J. I., Muranen, T. A., Barnes, D. R., Dennis, J., Michailidou, K., Bolla, M. K., Leslie, G., Aalfs, C. M., Balleine, R., Baxter, R., Braye, S., Carpenter, J., Dahlstrom, J., Forbes, J., Lee, C. S., Marsh, D., Morey, A., Pathmanathan, N., Scott, R., Simpson, P., Spigelman, A., Wilcken, N., Yip, D., Zeps, N., Adank, M. A., Adlard, J., Agata, S., Cadoo, K., Agnarsson, B. A., Ahearn, T., Aittomaki, K., Ambrosone, C. B., Andrews, L., Anton-Culver, H., Antonenkova, N. N., Arndt, V., Arnold, N., Aronson, K. J., Arun, B. K., Asseryanis, E., Auber, B., Auvinen, P., Azzollini, J., Balmana, J., Barkardottir, R. B., Barrowdale, D., Barwell, J., Beane Freeman, L. E., Beauparlant, C. J., Beckmann, M. W., Behrens, S., Benitez, J., Berger, R., Bermisheva, M., Blanco, A. M., Blomqvist, C., Bogdanova, N. V., Bojesen, A., Bojesen, S. E., Bonanni, B., Borg, A., Brady, A. F., Brauch, H., Brenner, H., Bruning, T., Burwinkel, B., Buys, S. S., Caldes, T., Caliebe, A., Caligo, M. A., Campa, D., Campbell, I. G., Canzian, F., Castelao, J. E., Chang-Claude, J., Chanock, S. J., Claes, K. B. M., Clarke, C. L., Collavoli, A., Conner, T. A., Cox, D. G., Cybulski, C., Czene, K., Daly, M. B., de la Hoya, M., Devilee, P., Diez, O., Ding, Y. C., Dite, G. S., Ditsch, N., Domchek, S. M., Dorfling, C. M., dos-Santos-Silva, I., Durda, K., Dwek, M., Eccles, D. M., Ekici, A. B., Eliassen, A. H., Ellberg, C., Eriksson, M., Evans, D. G., Fasching, P. A., Figueroa, J., Flyger, H., Foulkes, W. D., Friebel, T. M., Friedman, E., Gabrielson, M., Gaddam, P., Gago-Dominguez, M., Gao, C., Gapstur, S. M., Garber, J., Garcia-Closas, M., Garcia-Saenz, J. A., Gaudet, M. M., Gayther, S. A., Belotti, M., Bertrand, O., Birot, A. -M., Buecher, B., Caputo, S., Dupre, A., Fourme, E., Gauthier-Villars, M., Golmard, L., Le Mentec, M., Moncoutier, V., de Pauw, A., Saule, C., Boutry-Kryza, N., Calender, A., Giraud, S., Leone, M., Bressac-de-Paillerets, B., Caron, O., Guillaud-Bataille, M., Bignon, Y. -J., Uhrhammer, N., Bonadona, V., Lasset, C., Berthet, P., Castera, L., Vaur, D., Bourdon, V., Nogues, C., Noguchi, T., Popovici, C., Remenieras, A., Sobol, H., Coupier, I., Pujol, P., Adenis, C., Dumont, A., Revillion, F., Muller, D., Barouk-Simonet, E., Bonnet, F., Bubien, V., Longy, M., Sevenet, N., Gladieff, L., Guimbaud, R., Feillel, V., Toulas, C., Dreyfus, H., Leroux, C. D., Peysselon, M., Rebischung, C., Legrand, C., Baurand, A., Bertolone, G., Coron, F., Faivre, L., Jacquot, C., Lizard, S., Kientz, C., Lebrun, M., Prieur, F., Fert-Ferrer, S., Mari, V., Venat-Bouvet, L., Bezieau, S., Delnatte, C., Mortemousque, I., Colas, C., Coulet, F., Soubrier, F., Warcoin, M., Bronner, M., Sokolowska, J., Collonge-Rame, M. -A., Damette, A., Gesta, P., Lallaoui, H., Chiesa, J., Molina-Gomes, D., Ingster, O., Manouvrier-Hanu, S., Lejeune, S., Giles, G. G., Glendon, G., Godwin, A. K., Goldberg, M. S., Goldgar, D. E., Guenel, P., Gutierrez-Barrera, A. M., Haeberle, L., Haiman, C. A., Hakansson, N., Hall, P., Hamann, U., Harrington, P. A., Hein, A., Heyworth, J., Hillemanns, P., Hollestelle, A., Hopper, J. L., Hosgood, H. D., Howell, A., Hu, C., Hulick, P. J., Hunter, D. J., Imyanitov, E. N., Aghmesheh, M., Greening, S., Amor, D., Gattas, M., Botes, L., Buckley, M., Friedlander, M., Koehler, J., Meiser, B., Saleh, M., Salisbury, E., Trainer, A., Tucker, K., Antill, Y., Dobrovic, A., Fellows, A., Fox, S., Harris, M., Nightingale, S., Phillips, K., Sambrook, J., Thorne, H., Armitage, S., Arnold, L., Kefford, R., Kirk, J., Rickard, E., Bastick, P., Beesley, J., Hayward, N., Spurdle, A., Walker, L., Beilby, J., Saunders, C., Bennett, I., Blackburn, A., Bogwitz, M., Gaff, C., Lindeman, G., Pachter, N., Scott, C., Sexton, A., Visvader, J., Taylor, J., Winship, I., Brennan, M., Brown, M., French, J., Edwards, S., Burgess, M., Burke, J., Patterson, B., Butow, P., Culling, B., Caldon, L., Callen, D., Chauhan, D., Eisenbruch, M., Heiniger, L., Chauhan, M., Christian, A., Dixon, J., Kidd, A., Cohen, P., Colley, A., Fenton, G., Crook, A., Dickson, R., Field, M., Cui, J., Cummings, M., Dawson, S. -J., Defazio, A., Delatycki, M., Dudding, T., Edkins, T., Farshid, G., Flanagan, J., Fong, P., Forrest, L., Gallego-Ortega, D., George, P., Gill, G., Kollias, J., Haan, E., Hart, S., Jenkins, M., Hunt, C., Lakhani, S., Lipton, L., Lobb, L., Mann, G., Mclachlan, S. A., O'Connell, S., O'Sullivan, S., Pieper, E., Robinson, B., Saunus, J., Scott, E., Shelling, A., Williams, R., Young, M. A., Isaacs, C., Jakimovska, M., Jakubowska, A., James, P., Janavicius, R., Janni, W., John, E. M., Jones, M. E., Jung, A., Kaaks, R., Karlan, B. Y., Khusnutdinova, E., Kitahara, C. M., Konstantopoulou, I., Koutros, S., Kraft, P., Lambrechts, D., Lazaro, C., Le Marchand, L., Lester, J., Lesueur, F., Lilyquist, J., Loud, J. T., K. H., Lu, Luben, R. N., Lubinski, J., Mannermaa, A., Manoochehri, M., Manoukian, S., Margolin, S., Martens, J. W. M., Maurer, T., Mavroudis, D., Mebirouk, N., Meindl, A., Menon, U., Miller, A., Montagna, M., Nathanson, K. L., Neuhausen, S. L., Newman, W. G., Nguyen-Dumont, T., Nielsen, F. C., Nielsen, S., Nikitina-Zake, L., Offit, K., Olah, E., Olopade, O. I., Olshan, A. F., Olson, J. E., Olsson, H., Osorio, A., Ottini, L., Peissel, B., Peixoto, A., Peto, J., Plaseska-Karanfilska, D., Pocza, T., Presneau, N., Pujana, M. A., Punie, K., Rack, B., Rantala, J., Rashid, M. U., Rau-Murthy, R., Rennert, G., Lejbkowicz, F., Rhenius, V., Romero, A., Rookus, M. A., Ross, E. A., Rossing, M., Rudaitis, V., Ruebner, M., Saloustros, E., Sanden, K., Santamarina, M., Scheuner, M. T., Schmutzler, R. K., Schneider, M., Senter, L., Shah, M., Sharma, P., Shu, X. -O., Simard, J., Singer, C. F., Sohn, C., Soucy, P., Southey, M. C., Spinelli, J. J., Steele, L., Stoppa-Lyonnet, D., Tapper, W. J., Teixeira, M. R., Terry, M. B., Thomassen, M., Thompson, J., Thull, D. L., Tischkowitz, M., Tollenaar, R. A. E. M., Torres, D., Troester, M. A., Truong, T., Tung, N., Untch, M., Vachon, C. M., van Rensburg, E. J., van Veen, E. M., Vega, A., Viel, A., Wappenschmidt, B., Weitzel, J. N., Wendt, C., Wieme, G., Wolk, A., Yang, X. R., Zheng, W., Ziogas, A., Zorn, K. K., Dunning, A. M., Lush, M., Wang, Q., Mcguffog, L., Parsons, M. T., Pharoah, P. D. P., Fostira, F., Toland, A. E., Andrulis, I. L., Ramus, S. J., Swerdlow, A. J., Greene, M. H., Chung, W. K., Milne, R. L., Chenevix-Trench, G., Dork, T., Schmidt, M. K., Easton, D. F., Radice, P., Hahnen, E., Antoniou, A. C., Couch, F. J., Nevanlinna, H., Surralles, J., Peterlongo, P., Caleca, Laura [0000-0002-3381-7493], Muranen, Taru A. [0000-0002-5895-1808], Dennis, Joe [0000-0003-4591-1214], Adlard, Julian [0000-0002-1693-0435], Arndt, Volker [0000-0001-9320-8684], Auber, Bernd [0000-0003-1880-291X], Bonanni, Bernardo [0000-0003-3589-2128], Brauch, Hiltrud [0000-0001-7531-2736], Devilee, Peter [0000-0002-8023-2009], Foulkes, William D. [0000-0001-7427-4651], Isaacs, Claudine [0000-0002-9646-1260], Jakimovska, Milena [0000-0002-1506-0669], Konstantopoulou, Irene [0000-0002-0470-0309], Lesueur, Fabienne [0000-0001-7404-4549], Menon, Usha [0000-0003-3708-1732], Miller, Austin [0000-0001-9739-8462], Peto, Julian [0000-0002-1685-8912], Punie, Kevin [0000-0002-1162-7963], Romero, Atocha [0000-0002-1634-7397], Saloustros, Emmanouil [0000-0002-0485-0120], Scott, Christopher [0000-0003-1340-0647], Viel, Alessandra [0000-0003-2804-0840], Wieme, Greet [0000-0003-2718-5300], Zheng, Wei [0000-0003-1226-070X], Ziogas, Argyrios [0000-0003-4529-3727], Greene, Mark H. [0000-0003-1852-9239], Nevanlinna, Heli [0000-0002-0916-2976], Peterlongo, Paolo [0000-0001-6951-6855], Apollo - University of Cambridge Repository, Medical Oncology, Department of Genetics and Microbiology, Universitat Autònoma de Barcelona (UAB), IFOM, Istituto FIRC di Oncologia Molecolare (IFOM), Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Department of Clinical Genetics, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), Yorkshire Regional Genetics Service, Department of Pathology, University Hospital and University of Iceland School of Medicine, Division of Oncology, Department of Gynaecology and Obstetrics, University Hospital Schleswig–Holstein, Università degli Studi di Milano [Milano] (UNIMI), Medical Oncology Department, Vall d'Hebron University Hospital [Barcelona], University of Iceland [Reykjavik]-Landspitali - University Hospital, Centre for Cancer Genetic Epidemiology, University of Cambridge [UK] (CAM), Leicestershire Clinical Genetics Service, University Hospitals Leicester, Occupational and Environmental Epidemiology Branch [Bethesda, Maryland], Division of Cancer Epidemiology and Genetics [Bethesda, Maryland], National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH)-National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Laboratoire Interuniversitaire des Systèmes Atmosphériques (LISA (UMR_7583)), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Departemento Genetica Humana, Centro Nacional Investigaciones Oncologicas, Chaim Sheba Medical Center, Institute of Biochemistry and Genetics of Ufa Scientific Centre, Russian Academy of Sciences [Moscow] (RAS), Department of Oncology, Department of Obstetrics and Gynaecology (MHH), Hannover Medical School [Hannover] (MHH), Division of Cancer Prevention and Genetics, Department of Oncology, Clinical Sciences, Lund University [Lund]-Skåne University Hospital, North West Thames Regional Genetics, Northwick Park Hospital, Dr. Margarete Fischer-Bosch Institute for Clinical Pharmacology [Stuttgart], Division of Clinical Epidemiology and Aging Research, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Molecular Epidemiology Research Group, Department of Internal Medicine, Huntsman Cancer Institute, Molecular Oncology Laboratory, Hospital Clínico San Carlos, Section of Genetic Oncology, University of Pisa - Università di Pisa, Department of Cancer Epidemiology, Division of Cancer Epidemiology, Division of Cancer Epidemiology and Genetics, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Genetics and Pathology, International Hereditary Cancer Centre-Pomeranian Medical University [Szczecin] (PUM), Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], Division of Population Science, Fox Chase Cancer Center, Department of Human Genetics & Department of Pathology, Leiden University Medical Center (LUMC), Oncogenetics Laboratory, Vall d'Hebron Institute of Oncology (VHIO), Department of Obstetrics and Gynecology [Munich, Germany], University-Hospital Munich-Großhadern [München]-Ludwig Maximilian University [Munich] (LMU), Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], Wessex clinical genetics service, Lund University Hospital, Department of Genomic Medicine, University of Manchester [Manchester], Department of Breast Surgery, Herlev and Gentofte Hospital, Department of Human Genetics [Montréal], McGill University = Université McGill [Montréal, Canada], The Susanne Levy Gertner Oncogenetics Unit, Institute of Human Genetics, National Institutes of Health [Bethesda] (NIH), Epidemiology Research Program, American Cancer Society, Department of Preventive Medicine, University of Southern California (USC)-Keck School of Medicine [Los Angeles], University of Southern California (USC), University of Melbourne, Ontario Cancer Genetics Network, Cancer Care Ontario, Department of Pathology and Laboratory Medicine, University of Kansas Medical Center [Kansas City, KS, USA], International Agency for Cancer Research (IACR), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of OB/Gyn, University Breast Center Franconia, Univeristy Hospital Erlangen, Molecular Genetics of Breast Cancer, Centre for Cancer Genetic Epidemiology [Cambridge], University of Cambridge [UK] (CAM)-Department of Oncology, Department of Medical Oncology, Josephine Nefkens Institute and Daniel den Hoed Cancer Center, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Centre for MEGA Epidemiology, The University of Melbourne, Victoria, Australia, The Christie, Department of Statistics, Penn State University, University of Pennsylvania [Philadelphia], Laboratory of Molecular Oncology, N.N. Petrov Institute of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Department of Molecular and Regenerative Medicine, Hematology, Oncology and Transfusion, Vilnius University [Vilnius]-Hospital Santariskiu Clinics, Department of Gynecology and Obstetrics, Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Department of Epidemiology, Cancer Prevention Institute of California, Unit of Nutrition and Cancer, Women's Cancer Program, Samuel Oschin Comprehensive Cancer Institute, Institute of Biochemistry and Genetics [Bashkortostan Republic, Russia], Russian Academy of Sciences / Ufa Scientific Centre [Bashkortostan Republic, Russia]], National Center for Scientific Research 'Demokritos' (NCSR), Harvard School of Public Health, Laboratory for translational genetics Leuven, Genetic Counseling and Hereditary Cancer Programme, Catalan Institute of Oncology, University of Hawai‘i [Mānoa] (UHM), Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Clinical Genetics Branch, Strangeways Research Laboratory, Unit of Medical Genetics, Fondazione IRCCS INT, Department of Gynaecology and Obstetrics, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Institute for Women's Health [London], University College London Hospitals (UCLH), Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IOV - IRCCS, Department of Medicine, Medical Genetics, Abramson Cancer Center-Perelman School of Medicine, Department of Population Sciences, Beckman Research Institute of City of Hope, Section Génétique - Groupe Prédispositions génétiques au cancer, Centre International de Recherche contre le Cancer (CIRC), Clinical Genetics Service, Memorial Sloane Kettering Cancer Center [New York], Department of Molecular Genetics and Department of Chemotherapy, National Institute of Oncology, University of Chicago, Recherches épidémiologiques et statistiques sur l'environnement et la santé., Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Human Genetics Group, Spanish National Cancer Research Centre, Department of Molecular Medicine, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Department of Genetics, Portuguese Oncology Institute, Non-Communicable Disease Epidemiology Unit, London School of Hygiene and Tropical Medicine (LSHTM), University of Munich, Karolinska University Hospital [Stockholm], Umm Al-Qura University, Department of Community Medicine and Epidemiology, CHS National Cancer Control Center, Netherlands Cancer Institute, IT University of Copenhagen (ITU), Division of Molecular Gyneco-Oncology, Department of Gynaecology and Obstetrics, Clinical Center Un, Queen's University [Belfast] (QUB), Vanderbilt Epidemiology Center, Institute for Medicine and Public Health, Vanderbilt University School of Medicine [Nashville], Laboratoire de Génomique des Cancers, Université Laval [Québec] (ULaval), Division of Special Gynecology, Medizinische Universität Wien = Medical University of Vienna-Department of OB/GYN, Division Molecular Biology of Breast Cancer, Department of Gynecology and Obstetrics, Universität Heidelberg [Heidelberg], Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec, Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto = University of Porto, Department of Epidemiology [Columbia University], Columbia University [New York]-Columbia Mailman School of Public Health, Columbia University [New York], Odense University Hospital, Instituto de Genética Humana, Pontificia Universidad Javeriana (PUJ), HELIOS Hospital Berlin-Buch, Cancer Genetics Laboratory, University of Pretoria [South Africa], Genomic Medicine Group, Universidade de Santiago de Compostela [Spain] (USC ), Division of Experimental Oncology 1, Centro di Riferimento Oncologico (CRO), Division of Molecular Gyneco-Oncology, Department of Gynaecology and Obstetrics, City of Hope Comprehensive Cancer Center and Department of Population Sciences, Beckman Research Institute, Center for Astrophysical Sciences [Baltimore], Johns Hopkins University (JHU), European Bioinformatics Institute [Hinxton] (EMBL-EBI), EMBL Heidelberg, University of Science and Technology Beijing [Beijing] (USTB), University of Cambridge [UK] (CAM)-Department of Public Health and Primary Care-Centre for Cancer Genetic Epidemiology, Université de Pau et des Pays de l'Adour (UPPA), Department of Molecular Virology, Immunology and Medical Genetics [Colombus], Ohio State University [Columbus] (OSU)-College of Medicine and Public Health [Colombus], Departments of Molecular Genetics and Laboratory Medicine and Pathobiology, University of Toronto-Cancer Care Ontario, The institute of cancer research [London], Department of Medical Genetics, Mayo Clinic, Cancer Epidemiology Centre, Cancer Council Victoria, Queensland Institute of Medical Research, Cancer Research U.K. Genetic Epidemiology Unit, Unit of Genetic Susceptibility to Cancer, Department of Experimental Oncology and Molecular Medici, Department of Laboratory Medicine and Pathology, Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine-Fondazione IRCCS Istituto Nazionale Tumori (INT), Muranen, Taru A [0000-0002-5895-1808], Foulkes, William D [0000-0001-7427-4651], Greene, Mark H [0000-0003-1852-9239], Institut Català de la Salut, [Figlioli G, Catucci I] IFOM - the FIRC Institute for Molecular Oncology, Genome Diagnostics Program, Milan, Italy. [Bogliolo M, Pujol R] Department of Genetics and Microbiology, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain. Center for Biomedical Network Research on Rare Diseases (CIBERER), Madrid, Spain. Institute of Biomedical Research, Sant Pau Hospital, Barcelona, Spain. [Caleca L] Fondazione IRCCS Istituto Nazionale dei Tumori, Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Research, Milan, Italy. [Lasheras SV] Department of Genetics and Microbiology, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain. [Balmaña J] High Risk and Cancer Prevention Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Diez O] Oncogenetics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Genètica, Vall d’Hebron Hospital Universitari, Barcelona, Spain, Hospital Universitari Vall d'Hebron, University of Iceland [Reykjavik], Università degli Studi di Milano = University of Milan (UNIMI), Universiteit Leiden-Universiteit Leiden, University of Pennsylvania-University of Pennsylvania, University of Pennsylvania, Georgetown University [Washington] (GU), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Universität Heidelberg [Heidelberg] = Heidelberg University, European Project: 634935,H2020,H2020-PHC-2014-two-stage,BRIDGES(2015), European Project: 633784,H2020,H2020-PHC-2014-two-stage,B-CAST(2015), European Project: 223175,EC:FP7:HEALTH,FP7-HEALTH-2007-B,COGS(2009), Human Genetics, Vall d'Hebron Barcelona Hospital Campus, Autonomous University of Barcelona, Universitat Autònoma de Barcelona [Barcelona] (UAB), Università degli studi di Milano [Milano], University Hospitals of Leicester, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Department of Biology, University of Pisa, Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pomeranian Medical University-International Hereditary Cancer Centre, McGill University, University of Kansas Medical Center [Lawrence], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Oncology-University of Cambridge [UK] (CAM), Heinrich-Heine-Universität Düsseldorf [Düsseldorf], Cancer et génôme: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, MINES ParisTech - École nationale supérieure des mines de Paris-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Technical University of Munich (TUM), Università degli Studi di Roma 'La Sapienza' [Rome], IT University of Copenhagen, Laval University [Québec], Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Pontificia Universidad Javeriana, University of Santiago de Compostela, Læknadeild (HÍ), Faculty of Medicine (UI), Biomedical Center (UI), Lífvísindasetur (HÍ), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), MINES ParisTech - École nationale supérieure des mines de Paris, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Universidade do Porto, Ministerio de Economía y Competitividad (España), Unión Europea. Comisión Europea, Against Breast Cancer, Cancer Research UK (Reino Unido), Unión Europea. Comisión Europea. H2020, Cancer UK Grant, Canadian Institutes of Health Research, Ministère de Économie, de la science et de innovation (Canadá), NIH - National Cancer Institute (NCI) (Estados Unidos), Dutch Cancer Society (Holanda), Instituto de Salud Carlos III, Xunta de Galicia (España), Canadian Cancer Society, California Breast Cancer Research Program, California Department of Public Health, Medical Research Council (Reino Unido), Free State of Saxony, Germany (LIFE -Leipzig Research Centre for Civilization Diseases), Federal Ministry of Education & Research (Alemania), German Cancer Aid, Helsinki University Central Hospital Research Fund, Finlands Akademi (Finlandia), Deutsche Forschungsgemeinschaft (Alemania), Russian Foundation for Basic Research, Ministry of Science and Higher Education (Rusia), National Health and Medical Research Council (Australia), Biobanking and BioMolecular resources Research Infrastructure (Países Bajos), Estée Lauder Companies’ Breast Cancer Campaign, Swedish Research Council, NIH - National Cancer Institute (NCI). Specialized Programs of Research Excellence (SPOREs) (Estados Unidos), Lon V. Smith Foundation, Research Coincil of Lithuania, Italian Association for Cancer Research, University of Kansas. Cancer Center (Estados Unidos), Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), French National Cancer Institute, Netherlands Organisation for Health Research and Development, Pink Ribbons Project, United States of Department of Health & Human Services, HUS Gynecology and Obstetrics, Clinicum, University of Helsinki, Medicum, Kristiina Aittomäki / Principal Investigator, HUSLAB, University Management, HUS Comprehensive Cancer Center, Biosciences, Helsinki University Hospital, and Lietuvos Mokslo Taryba (Lituania)
Subjects: 0301 basic medicine, Gene mutation, Càncer - Aspectes genètics, chemistry.chemical_compound, 0302 clinical medicine, Breast cancer, Mama - Càncer, Fanconi anemia, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Brjóstakrabbamein, Medicine and Health Sciences, Pharmacology (medical), FANCM, 631/208/68, skin and connective tissue diseases, Cancer genetics, Triple-negative breast cancer, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Manchester Cancer Research Centre, Otros calificadores::Otros calificadores::/genética [Otros calificadores], article, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, Oncology, 030220 oncology & carcinogenesis, Neoplasms::Neoplasms by Site::Breast Neoplasms::Triple Negative Breast Neoplasms [DISEASES], [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Life Sciences & Biomedicine, 3122 Cancers, ABCTB Investigators, lcsh:RC254-282, KConFab, Olaparib, Càncer de mama, GEMO Study Collaborators, 03 medical and health sciences, breast cancer, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, SDG 3 - Good Health and Well-being, 631/67/68, medicine, Other subheadings::Other subheadings::/genetics [Other subheadings], Erfðafræði, Radiology, Nuclear Medicine and imaging, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, ddc:610, Risk factor, CHEK2, Krabbamein, Cancer och onkologi, FancM, Science & Technology, cancer, MUTATIONS, business.industry, ResearchInstitutes_Networks_Beacons/mcrc, Biology and Life Sciences, nutritional and metabolic diseases, cancer genetics, medicine.disease, GENE, Expressió gènica, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, neoplasias::neoplasias por localización::neoplasias de la mama::neoplasias de mama triple negativos [ENFERMEDADES], 030104 developmental biology, chemistry, 692/4028/67/68, Cancer and Oncology, FANCONI-ANEMIA, Cancer research, gene expression, C.5791C-GREATER-THAN-T, business
Abstract: Publisher's version (útgefin grein), Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors., Peterlongo laboratory is supported by Associazione Italiana Ricerca sul Cancro (AIRC; IG2015 no.16732) to P. Peterlongo and by a fellowship from Fondazione Umberto Veronesi to G. Figlioli. Surrallés laboratory is supported by the ICREA-Academia program, the Spanish Ministry of Health (projects FANCOSTEM and FANCOLEN), the Spanish Ministry of Economy and Competiveness (projects CB06/07/0023 and RTI2018-098419-B-I00), the European Commission (EUROFANCOLEN project HEALTH-F5-2012-305421 and P-SPHERE COFUND project), the Fanconi Anemia Research Fund Inc, and the “Fondo Europeo de Desarrollo Regional, una manera de hacer Europa” (FEDER). CIBERER is an initiative of the Instituto de Salud Carlos III, Spain. BCAC: we thank all the individuals who took part in these studies and all the researchers, clinicians, technicians and administrative staff who have enabled this work to be carried out. ABCFS thank Maggie Angelakos, Judi Maskiell, Tu Nguyen-Dumont is a National Breast Cancer Foundation (Australia) Career Development Fellow. ABCS thanks the Blood bank Sanquin, The Netherlands. Samples are made available to researchers on a non-exclusive basis. BCEES thanks Allyson Thomson, Christobel Saunders, Terry Slevin, BreastScreen Western Australia, Elizabeth Wylie, Rachel Lloyd. The BCINIS study would not have been possible without the contributions of Dr. Hedy Rennert, Dr. K. Landsman, Dr. N. Gronich, Dr. A. Flugelman, Dr. W. Saliba, Dr. E. Liani, Dr. I. Cohen, Dr. S. Kalet, Dr. V. Friedman, Dr. O. Barnet of the NICCC in Haifa, and all the contributing family medicine, surgery, pathology and oncology teams in all medical institutes in Northern Israel. The BREOGAN study would not have been possible without the contributions of the following: Manuela Gago-Dominguez, Jose Esteban Castelao, Angel Carracedo, Victor Muñoz Garzón, Alejandro Novo Domínguez, Maria Elena Martinez, Sara Miranda Ponte, Carmen Redondo Marey, Maite Peña Fernández, Manuel Enguix Castelo, Maria Torres, Manuel Calaza (BREOGAN), José Antúnez, Máximo Fraga and the staff of the Department of Pathology and Biobank of the University Hospital Complex of Santiago-CHUS, Instituto de Investigación Sanitaria de Santiago, IDIS, Xerencia de Xestion Integrada de Santiago-SERGAS; Joaquín González-Carreró and the staff of the Department of Pathology and Biobank of University Hospital Complex of Vigo, Instituto de Investigacion Biomedica Galicia Sur, SERGAS, Vigo, Spain. BSUCH thanks Peter Bugert, Medical Faculty Mannheim. CBCS thanks study participants, co-investigators, collaborators and staff of the Canadian Breast Cancer Study, and project coordinators Agnes Lai and Celine Morissette. CCGP thanks Styliani Apostolaki, Anna Margiolaki, Georgios Nintos, Maria Perraki, Georgia Saloustrou, Georgia Sevastaki, Konstantinos Pompodakis. CGPS thanks staff and participants of the Copenhagen General Population Study. For the excellent technical assistance: Dorthe Uldall Andersen, Maria Birna Arnadottir, Anne Bank, Dorthe Kjeldgård Hansen. The Danish Cancer Biobank is acknowledged for providing infrastructure for the collection of blood samples for the cases. Investigators from the CPS-II cohort thank the participants and Study Management Group for their invaluable contributions to this research. They also acknowledge the contribution to this study from central cancer registries supported through the Centers for Disease Control and Prevention National Program of Cancer Registries, as well as cancer registries supported by the National Cancer Institute Surveillance Epidemiology and End Results program. The CTS Steering Committee includes Leslie Bernstein, Susan Neuhausen, James Lacey, Sophia Wang, Huiyan Ma, and Jessica Clague DeHart at the Beckman Research Institute of City of Hope, Dennis Deapen, Rich Pinder, and Eunjung Lee at the University of Southern California, Pam Horn-Ross, Peggy Reynolds, Christina Clarke Dur and David Nelson at the Cancer Prevention Institute of California, Hoda Anton-Culver, Argyrios Ziogas, and Hannah Park at the University of California Irvine, and Fred Schumacher at Case Western University. DIETCOMPLYF thanks the patients, nurses and clinical staff involved in the study. The DietCompLyf study was funded by the charity Against Breast Cancer (Registered Charity Number 1121258) and the NCRN. We thank the participants and the investigators of EPIC (European Prospective Investigation into Cancer and Nutrition). ESTHER thanks Hartwig Ziegler, Sonja Wolf, Volker Hermann, Christa Stegmaier, Katja Butterbach. FHRISK thanks NIHR for funding. GC-HBOC thanks Stefanie Engert, Heide Hellebrand, Sandra Kröber and LIFE - Leipzig Research Centre for Civilization Diseases (Markus Loeffler, Joachim Thiery, Matthias Nüchter, Ronny Baber). The GENICA Network: Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, and University of Tübingen, Germany [HB, Wing-Yee Lo], German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) [HB], Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy - EXC 2180 - 390900677 [HB], Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany [Yon-Dschun Ko, Christian Baisch], Institute of Pathology, University of Bonn, Germany [Hans-Peter Fischer], Molecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany [Ute Hamann], Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, Germany [TB, Beate Pesch, Sylvia Rabstein, Anne Lotz]; and Institute of Occupational Medicine and Maritime Medicine, University Medical Center Hamburg-Eppendorf, Germany [Volker Harth]. HABCS thanks Michael Bremer. HEBCS thanks Heidi Toiminen, Kristiina Aittomäki, Irja Erkkilä and Outi Malkavaara. HMBCS thanks Peter Hillemanns, Hans Christiansen and Johann H. Karstens. HUBCS thanks Shamil Gantsev. KARMA thanks the Swedish Medical Research Counsel. KBCP thanks Eija Myöhänen, Helena Kemiläinen. LMBC thanks Gilian Peuteman, Thomas Van Brussel, EvyVanderheyden and Kathleen Corthouts. MABCS thanks Milena Jakimovska (RCGEB “Georgi D. Efremov), Katerina Kubelka, Mitko Karadjozov (Adzibadem-Sistina” Hospital), Andrej Arsovski and Liljana Stojanovska (Re-Medika” Hospital) for their contributions and commitment to this study. MARIE thanks Petra Seibold, Dieter Flesch-Janys, Judith Heinz, Nadia Obi, Alina Vrieling, Sabine Behrens, Ursula Eilber, Muhabbet Celik, Til Olchers and Stefan Nickels. MBCSG (Milan Breast Cancer Study Group) thanks Daniela Zaffaroni, Irene Feroce, and the personnel of the Cogentech Cancer Genetic Test Laboratory. We thank the coordinators, the research staff and especially the MMHS participants for their continued collaboration on research studies in breast cancer. MSKCC thanks Marina Corines and Lauren Jacobs. MTLGEBCS would like to thank Martine Tranchant (CHU de Québec Research Center), Marie-France Valois, Annie Turgeon and Lea Heguy (McGill University Health Center, Royal Victoria Hospital; McGill University) for DNA extraction, sample management and skillful technical assistance. J.S. is Chairholder of the Canada Research Chair in Oncogenetics. NBHS thanks study participants and research staff for their contributions and commitment to the studies. We would like to thank the participants and staff of the Nurses’ Health Study and Nurses’ Health Study II for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. The study protocol was approved by the institutional review boards of the Brigham and Women’s Hospital and Harvard T.H. Chan School of Public Health, and those of participating registries as required. The authors assume full responsibility for analyses and interpretation of these data. OFBCR thanks Teresa Selander and Nayana Weerasooriya. ORIGO thanks E. Krol-Warmerdam, and J. Blom for patient accrual, administering questionnaires, and managing clinical information. PBCS thanks Louise Brinton, Mark Sherman, Neonila Szeszenia-Dabrowska, Beata Peplonska, Witold Zatonski, Pei Chao and Michael Stagner. The ethical approval for the POSH study is MREC /00/6/69, UKCRN ID: 1137. We thank staff in the Experimental Cancer Medicine Centre (ECMC) supported Faculty of Medicine Tissue Bank and the Faculty of Medicine DNA Banking resource. PREFACE thanks Sonja Oeser and Silke Landrith. PROCAS thanks NIHR for funding. RBCS thanks Petra Bos, Jannet Blom, Ellen Crepin, Elisabeth Huijskens, Anja Kromwijk-Nieuwlaat, Annette Heemskerk, the Erasmus MC Family Cancer Clinic. We thank the SEARCH and EPIC teams. SKKDKFZS thanks all study participants, clinicians, family doctors, researchers and technicians for their contributions and commitment to this study. We thank the SUCCESS Study teams in Munich, Duessldorf, Erlangen and Ulm. SZBCS thanks Ewa Putresza. UCIBCS thanks Irene Masunaka. UKBGS thanks Breast Cancer Now and the Institute of Cancer Research for support and funding of the Breakthrough Generations Study, and the study participants, study staff, and the doctors, nurses and other health care providers and health information sources who have contributed to the study. We acknowledge NHS funding to the Royal Marsden/ICR NIHR Biomedical Research Centre. CIMBA: we are grateful to all the families and clinicians who contribute to the studies; Sue Healey, in particular taking on the task of mutation classification with the late Olga Sinilnikova; Maggie Angelakos, Judi Maskiell, Helen Tsimiklis; members and participants in the New York site of the Breast Cancer Family Registry; members and participants in the Ontario Familial Breast Cancer Registry; Vilius Rudaitis and Laimonas Griškevičius; Yuan Chun Ding and Linda Steele for their work in participant enrollment and biospecimen and data management; Bent Ejlertsen and Anne-Marie Gerdes for the recruitment and genetic counseling of participants; Alicia Barroso, Rosario Alonso and Guillermo Pita; all the individuals and the researchers who took part in CONSIT TEAM (Consorzio Italiano Tumori Ereditari Alla Mammella), thanks in particular: Giulia Cagnoli, Roberta Villa, Irene Feroce, Mariarosaria Calvello, Riccardo Dolcetti, Giuseppe Giannini, Laura Papi, Gabriele Lorenzo Capone, Liliana Varesco, Viviana Gismondi, Maria Grazia Tibiletti, Daniela Furlan, Antonella Savarese, Aline Martayan, Stefania Tommasi, Brunella Pilato, Isabella Marchi, Elena Bandieri, Antonio Russo, Daniele Calistri and the personnel of the Cogentech Cancer Genetic Test Laboratory, Milan, Italy. FPGMX: members of the Cancer Genetics group (IDIS): Ana Blanco, Miguel Aguado, Uxía Esperón and Belinda Rodríguez. We thank all participants, clinicians, family doctors, researchers, and technicians for their contributions and commitment to the DKFZ study and the collaborating groups in Lahore, Pakistan (Noor Muhammad, Sidra Gull, Seerat Bajwa, Faiz Ali Khan, Humaira Naeemi, Saima Faisal, Asif Loya, Mohammed Aasim Yusuf) and Bogota, Colombia (Diana Torres, Ignacio Briceno, Fabian Gil). Genetic Modifiers of Cancer Risk in BRCA1/2 Mutation Carriers (GEMO) study is a study from the National Cancer Genetics Network UNICANCER Genetic Group, France. We wish to pay a tribute to Olga M. Sinilnikova, who with Dominique Stoppa-Lyonnet initiated and coordinated GEMO until she sadly passed away on the 30th June 2014. The team in Lyon (Olga Sinilnikova, Mélanie Léoné, Laure Barjhoux, Carole Verny-Pierre, Sylvie Mazoyer, Francesca Damiola, Valérie Sornin) managed the GEMO samples until the biological resource centre was transferred to Paris in December 2015 (Noura Mebirouk, Fabienne Lesueur, Dominique Stoppa-Lyonnet). We want to thank all the GEMO collaborating groups for their contribution to this study. Drs.Sofia Khan, Irja Erkkilä and Virpi Palola; The Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON) consists of the following Collaborating Centers: Netherlands Cancer Institute (coordinating center), Amsterdam, NL: M.A. Rookus, F.B.L. Hogervorst, F.E. van Leeuwen, M.A. Adank, M.K. Schmidt, N.S. Russell, D.J. Jenner; Erasmus Medical Center, Rotterdam, NL: J.M. Collée, A.M.W. van den Ouweland, M.J. Hooning, C.M. Seynaeve, C.H.M. van Deurzen, I.M. Obdeijn; Leiden University Medical Center, NL: C.J. van Asperen, P. Devilee, T.C.T.E.F. van Cronenburg; Radboud University Nijmegen Medical Center, NL: C.M. Kets, A.R. Mensenkamp; University Medical Center Utrecht, NL: M.G.E.M. Ausems, M.J. Koudijs; Amsterdam Medical Center, NL: C.M. Aalfs, H.E.J. Meijers-Heijboer; VU University Medical Center, Amsterdam, NL: K. van Engelen, J.J.P. Gille; Maastricht University Medical Center, NL: E.B. Gómez-Garcia, M.J. Blok; University of Groningen, NL: J.C. Oosterwijk, A.H. van der Hout, M.J. Mourits, G.H. de Bock; The Netherlands Comprehensive Cancer Organisation (IKNL): S. Siesling, J.Verloop; The nationwide network and registry of histo- and cytopathology in The Netherlands (PALGA): A.W. van den Belt-Dusebout. HEBON thanks the study participants and the registration teams of IKNL and PALGA for part of the data collection. Overbeek; the Hungarian Breast and Ovarian Cancer Study Group members (Janos Papp, Aniko Bozsik, Zoltan Matrai, Miklos Kasler, Judit Franko, Maria Balogh, Gabriella Domokos, Judit Ferenczi, Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary) and the clinicians and patients for their contributions to this study; HVH (University Hospital Vall d’Hebron) the authors acknowledge the Oncogenetics Group (VHIO) and the High Risk and Cancer Prevention Unit of the University Hospital Vall d’Hebron, Miguel Servet Progam (CP10/00617), and the Cellex Foundation for providing research facilities and equipment; the ICO Hereditary Cancer Program team led by Dr. Gabriel Capella; the ICO Hereditary Cancer Program team led by Dr. Gabriel Capella; Dr Martine Dumont for sample management and skillful assistance; Catarina Santos and Pedro Pinto; members of the Center of Molecular Diagnosis, Oncogenetics Department and Molecular Oncology Research Center of Barretos Cancer Hospital; Heather Thorne, Eveline Niedermayr, all the kConFab investigators, research nurses and staff, the heads and staff of the Family Cancer Clinics, and the Clinical Follow Up Study (which has received funding from the NHMRC, the National Breast Cancer Foundation, Cancer Australia, and the National Institute of Health (USA)) for their contributions to this resource, and the many families who contribute to kConFab; the investigators of the Australia New Zealand NRG Oncology group; members and participants in the Ontario Cancer Genetics Network; Kevin Sweet, Caroline Craven, Julia Cooper, Amber Aielts, and Michelle O’Conor; Christina Selkirk; Helena Jernström, Karin Henriksson, Katja Harbst, Maria Soller, Ulf Kristoffersson; from Gothenburg Sahlgrenska University Hospital: Anna Öfverholm, Margareta Nordling, Per Karlsson, Zakaria Einbeigi; from Stockholm and Karolinska University Hospital: Anna von Wachenfeldt, Annelie Liljegren, Annika Lindblom, Brita Arver, Gisela Barbany Bustinza; from Umeå University Hospital: Beatrice Melin, Christina Edwinsdotter Ardnor, Monica Emanuelsson; from Uppsala University: Hans Ehrencrona, Maritta Hellström Pigg, Richard Rosenquist; from Linköping University Hospital: Marie Stenmark-Askmalm, Sigrun Liedgren; Cecilia Zvocec, Qun Niu; Joyce Seldon and Lorna Kwan; Dr. Robert Nussbaum, Beth Crawford, Kate Loranger, Julie Mak, Nicola Stewart, Robin Lee, Amie Blanco and Peggy Conrad and Salina Chan; Carole Pye, Patricia Harrington and Eva Wozniak. OSUCCG thanks Kevin Sweet, Caroline Craven, Julia Cooper, Michelle O’Conor and Amber Aeilts. BCAC is funded by Cancer Research UK [C1287/A16563, C1287/A10118], the European Union’s Horizon 2020 Research and Innovation Programme (grant numbers 634935 and 633784 for BRIDGES and B-CAST respectively), and by the European Community´s Seventh Framework Programme under grant agreement number 223175 (grant number HEALTH-F2-2009-223175) (COGS). The EU Horizon 2020 Research and Innovation Programme funding source had no role in study design, data collection, data analysis, data interpretation or writing of the report. Genotyping of the OncoArray was funded by the NIH Grant U19 CA148065, and Cancer UK Grant C1287/A16563 and the PERSPECTIVE project supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research (grant GPH-129344) and, the Ministère de l’Économie, Science et Innovation du Québec through Genome Québec and the PSRSIIRI-701 grant, and the Quebec Breast Cancer Foundation. The Australian Breast Cancer Family Study (ABCFS) was supported by grant UM1 CA164920 from the National Cancer Institute (USA). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the USA Government or the BCFR. The ABCFS was also supported by the National Health and Medical Research Council of Australia, the New South Wales Cancer Council, the Victorian Health Promotion Foundation (Australia) and the Victorian Breast Cancer Research Consortium. J.L.H. is a National Health and Medical Research Council (NHMRC) Senior Principal Research Fellow. M.C.S. is a NHMRC Senior Research Fellow. The ABCS study was supported by the Dutch Cancer Society [grants NKI 2007-3839; 2009 4363]. The Australian Breast Cancer Tissue Bank (ABCTB) was supported by the National Health and Medical Research Council of Australia, The Cancer Institute NSW and the National Breast Cancer Foundation. The AHS study is supported by the intramural research program of the National Institutes of Health, the National Cancer Institute (grant number Z01-CP010119), and the National Institute of Environmental Health Sciences (grant number Z01-ES049030). The work of the BBCC was partly funded by ELAN-Fond of the University Hospital of Erlangen. The BBCS is funded by Cancer Research UK and Breast Cancer Now and acknowledges NHS funding to the NIHR Biomedical Research Centre, and the National Cancer Research Network (NCRN). The BCEES was funded by the National Health and Medical Research Council, Australia and the Cancer Council Western Australia. For the BCFR-NY, BCFR-PA, BCFR-UT this work was supported by grant UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the BCFR. BCINIS study was funded by the BCRF (The Breast Cancer Research Foundation, USA). The BREast Oncology GAlician Network (BREOGAN) is funded by Acción Estratégica de Salud del Instituto de Salud Carlos III FIS PI12/02125/Cofinanciado FEDER; Acción Estratégica de Salud del Instituto de Salud Carlos III FIS Intrasalud (PI13/01136); Programa Grupos Emergentes, Cancer Genetics Unit, Instituto de Investigacion Biomedica Galicia Sur. Xerencia de Xestion Integrada de Vigo-SERGAS, Instituto de Salud Carlos III, Spain; Grant 10CSA012E, Consellería de Industria Programa Sectorial de Investigación Aplicada, PEME I + D e I + D Suma del Plan Gallego de Investigación, Desarrollo e Innovación Tecnológica de la Consellería de Industria de la Xunta de Galicia, Spain; Grant EC11-192. Fomento de la Investigación Clínica Independiente, Ministerio de Sanidad, Servicios Sociales e Igualdad, Spain; and Grant FEDER-Innterconecta. Ministerio de Economia y Competitividad, Xunta de Galicia, Spain. The BSUCH study was supported by the Dietmar-Hopp Foundation, the Helmholtz Society and the German Cancer Research Center (DKFZ). Sample collection and processing was funded in part by grants from the National Cancer Institute (NCI R01CA120120 and K24CA169004). CBCS is funded by the Canadian Cancer Society (grant # 313404) and the Canadian Institutes of Health Research. CCGP is supported by funding from the University of Crete. The CECILE study was supported by Fondation de France, Institut National du Cancer (INCa), Ligue Nationale contre le Cancer, Agence Nationale de Sécurité Sanitaire, de l’Alimentation, de l’Environnement et du Travail (ANSES), Agence Nationale de la Recherche (ANR). The CGPS was supported by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council, and Herlev and Gentofte Hospital. The American Cancer Society funds the creation, maintenance, and updating of the CPS-II cohort. The CTS was initially supported by the California Breast Cancer Act of 1993 and the California Breast Cancer Research Fund (contract 97-10500) and is currently funded through the National Institutes of Health (R01 CA77398, K05 CA136967, UM1 CA164917, and U01 CA199277). Collection of cancer incidence data was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885. The University of Westminster curates the DietCompLyf database funded by Against Breast Cancer Registered Charity No. 1121258 and the NCRN. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by: Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF) (Germany); the Hellenic Health Foundation, the Stavros Niarchos Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain); Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom). The ESTHER study was supported by a grant from the Baden Württemberg Ministry of Science, Research and Arts. Additional cases were recruited in the context of the VERDI study, which was supported by a grant from the German Cancer Aid (Deutsche Krebshilfe). FHRISK is funded from NIHR grant PGfAR 0707-10031. The GC-HBOC (German Consortium of Hereditary Breast and Ovarian Cancer) is supported by the German Cancer Aid (grant no 110837, coordinator: Rita K. Schmutzler, Cologne). This work was also funded by the European Regional Development Fund and Free State of Saxony, Germany (LIFE - Leipzig Research Centre for Civilization Diseases, project numbers 713-241202, 713-241202, 14505/2470, 14575/2470). The GENICA was funded by the Federal Ministry of Education and Research (BMBF) Germany grants 01KW9975/5, 01KW9976/8, 01KW9977/0 and 01KW0114, the Robert Bosch Foundation, Stuttgart, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, the Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, as well as the Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany. The GEPARSIXTO study was conducted by the German Breast Group GmbH. The GESBC was supported by the Deutsche Krebshilfe e. V. [70492] and the German Cancer Research Center (DKFZ). The HABCS study was supported by the Claudia von Schilling Foundation for Breast Cancer Research, by the Lower Saxonian Cancer Society, and by the Rudolf Bartling Foundation. The HEBCS was financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (266528), the Finnish Cancer Society, and the Sigrid Juselius Foundation. The HMBCS was supported by a grant from the German Research Foundation (Do 761/10-1). The HUBCS was supported by a grant from the German Federal Ministry of Research and Education (RUS08/017), and by the Russian Foundation for Basic Research and the Federal Agency for Scientific Organizations for support the Bioresource collections and RFBR grants 14-04-97088, 17-29-06014 and 17-44-020498. E.K was supported by the program for support the bioresource collections №007-030164/2 and study was performed as part of the assignment of the Ministry of Science and Higher Education of Russian Federation (№АААА-А16-116020350032-1). Financial support for KARBAC was provided through the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet, the Swedish Cancer Society, The Gustav V Jubilee foundation and Bert von Kantzows foundation. The KARMA study was supported by Märit and Hans Rausings Initiative Against Breast Cancer. The KBCP was financially supported by the special Government Funding (EVO) of Kuopio University Hospital grants, Cancer Fund of North Savo, the Finnish Cancer Organizations, and by the strategic funding of the University of Eastern Finland. LMBC is supported by the ‘Stichting tegen Kanker’. DL is supported by the FWO. The MABCS study is funded by the Research Centre for Genetic Engineering and Biotechnology “Georgi D. Efremov” and supported by the German Academic Exchange Program, DAAD. The MARIE study was supported by the Deutsche Krebshilfe e.V. [70-2892-BR I, 106332, 108253, 108419, 110826, 110828], the Hamburg Cancer Society, the German Cancer Research Center (DKFZ) and the Federal Ministry of Education and Research (BMBF) Germany [01KH0402]. MBCSG is supported by grants from the Italian Association for Cancer Research (AIRC) and by funds from the Italian citizens who allocated the 5/1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects “5 × 1000”). The MCBCS was supported by the NIH grants CA192393, CA116167, CA176785 an NIH Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201], and the Breast Cancer Research Foundation and a generous gift from the David F. and Margaret T. Grohne Family Foundation. MCCS cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian NHMRC grants 209057 and 396414, and by infrastructure provided by Cancer Council Victoria. Cases and their vital status were ascertained through the Victorian Cancer Registry (VCR) and the Australian Institute of Health and Welfare (AIHW), including the National Death Index and the Australian Cancer Database. The MEC was support by NIH grants CA63464, CA54281, CA098758, CA132839 and CA164973. The MISS study is supported by funding from ERC-2011-294576 Advanced grant, Swedish Cancer Society, Swedish Research Council, Local hospital funds, Berta Kamprad Foundation, Gunnar Nilsson. The MMHS study was supported by NIH grants CA97396, CA128931, CA116201, CA140286 and CA177150. MSKCC is supported by grants from the Breast Cancer Research Foundation and Robert and Kate Niehaus Clinical Cancer Genetics Initiative. The work of MTLGEBCS was supported by the Quebec Breast Cancer Foundation, the Canadian Institutes of Health Research for the “CIHR Team in Familial Risks of Breast Cancer” program – grant # CRN-87521 and the Ministry of Economic Development, Innovation and Export Trade – grant # PSR-SIIRI-701. The NBHS was supported by NIH grant R01CA100374. Biological sample preparation was conducted the Survey and Biospecimen Shared Resource, which is supported by P30 CA68485. The Northern California Breast Cancer Family Registry (NC-BCFR) and Ontario Familial Breast Cancer Registry (OFBCR) were supported by grant UM1 CA164920 from the National Cancer Institute (USA). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the USA Government or the BCFR. The Carolina Breast Cancer Study was funded by Komen Foundation, the National Cancer Institute (P50 CA058223, U54 CA156733, U01 CA179715), and the North Carolina University Cancer Research Fund. The NHS was supported by NIH grants P01 CA87969, UM1 CA186107, and U19 CA148065. The NHS2 was supported by NIH grants UM1 CA176726 and U19 CA148065. The ORIGO study was supported by the Dutch Cancer Society (RUL 1997-1505) and the Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL CP16). The PBCS was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. Genotyping for PLCO was supported by the Intramural Research Program of the National Institutes of Health, NCI, Division of Cancer Epidemiology and Genetics. The PLCO is supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics and supported by contracts from the Division of Cancer Prevention, National Cancer Institute, National Institutes of Health. The POSH study is funded by Cancer Research UK (grants C1275/A11699, C1275/C22524, C1275/A19187, C1275/A15956 and Breast Cancer Campaign 2010PR62, 2013PR044. PROCAS is funded from NIHR grant PGfAR 0707-10031. The RBCS was funded by the Dutch Cancer Society (DDHK 2004-3124, DDHK 2009-4318). SEARCH is funded by Cancer Research UK [C490/A10124, C490/A16561] and supported by the UK National Institute for Health Research Biomedical Research Centre at the University of Cambridge. The University of Cambridge has received salary support for PDPP from the NHS in the East of England through the Clinical Academic Reserve. The Sister Study (SISTER) is supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES044005 and Z01-ES049033). The Two Sister Study (2SISTER) was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES044005 and Z01-ES102245), and, also by a grant from Susan G. Komen for the Cure, grant FAS0703856. SKKDKFZS is supported by the DKFZ. The SMC is funded by the Swedish Cancer Foundation and the Swedish Research Council [grant 2017-00644 for the Swedish Infrastructure for Medical Population-based Life-course Environmental Research (SIMPLER)]. The SZBCS is financially supported under the program of Minister of Science and Higher Education “Regional Initiative of Excellence” in years 2019-2022, Grant No 002/RID/2018/19. The TNBCC was supported by: a Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a grant from the Breast Cancer Research Foundation, a generous gift from the David F. and Margaret T. Grohne Family Foundation. The UCIBCS component of this research was supported by the NIH [CA58860, CA92044] and the Lon V Smith Foundation [LVS39420]. The UKBGS is funded by Breast Cancer Now and the Institute of Cancer Research (ICR), London. ICR acknowledges NHS funding to the NIHR Biomedical Research Centre. The UKOPS study was funded by The Eve Appeal (The Oak Foundation) and supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. The USRT Study was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. CIMBA CIMBA: The CIMBA data management and data analysis were supported by Cancer Research – UK grants C12292/A20861, C12292/A11174. ACA is a Cancer Research -UK Senior Cancer Research Fellow. GCT and ABS are NHMRC Research Fellows. The PERSPECTIVE project was supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research, the Ministry of Economy, Science and Innovation through Genome Québec, and The Quebec Breast Cancer Foundation. BCFR: UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the BCFR. BFBOCC: Lithuania (BFBOCC-LT): Research Council of Lithuania grant SEN-18/2015 and Nr. P-MIP-19-164. BIDMC: Breast Cancer Research Foundation. BMBSA: Cancer Association of South Africa (PI Elizabeth J. van Rensburg). CNIO: Spanish Ministry of Health PI16/00440 supported by FEDER funds, the Spanish Ministry of Economy and Competitiveness (MINECO) SAF2014-57680-R and the Spanish Research Network on Rare diseases (CIBERER). COH-CCGCRN: Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under grant number R25CA112486, and RC4CA153828 (PI: J. Weitzel) from the National Cancer Institute and the Office of the Director, National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. CONSIT TEAM: Associazione Italiana Ricerca sul Cancro (AIRC; IG2014 no.15547) to P. Radice. Funds from Italian citizens who allocated the 5 × 1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects ‘5 × 1000’) to S. Manoukian. UNIROMA1: Italian Association for Cancer Research (AIRC; grant no. 21389) to L. Ottini. DFKZ: German Cancer Research Center. EMBRACE: Cancer Research UK Grants C1287/A10118 and C1287/A11990. D. Gareth Evans and Fiona Lalloo are supported by an NIHR grant to the Biomedical Research Centre, Manchester (IS-BRC-1215-20007). The Investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust are supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. Ros Eeles and Elizabeth Bancroft are supported by Cancer Research UK Grant C5047/A8385. Ros Eeles is also supported by NIHR support to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. FCCC: NIH/NCI grant P30-CA006927. The University of Kansas Cancer Center (P30 CA168524) and the Kansas Bioscience Authority Eminent Scholar Program. A.K.G. was funded by R0 1CA140323, R01 CA214545, and by the Chancellors Distinguished Chair in Biomedical Sciences Professorship. Ana Vega is supported by the Spanish Health Research Foundation, Instituto de Salud Carlos III (ISCIII), partially supported by FEDER funds through Research Activity Intensification Program (contract grant numbers: INT15/00070, INT16/00154, INT17/00133), and through Centro de Investigación Biomédica en Red de Enferemdades Raras CIBERER (ACCI 2016: ER17P1AC7112/2018); Autonomous Government of Galicia (Consolidation and structuring program: IN607B), and by the Fundación Mutua Madrileña (call 2018). GC-HBOC: German Cancer Aid (grant no 110837, Rita K. Schmutzler) and the European Regional Development Fund and Free State of Saxony, Germany (LIFE - Leipzig Research Centre for Civilization Diseases, project numbers 713-241202, 713-241202, 14505/2470, 14575/2470). GEMO: Ligue Nationale Contre le Cancer; the Association “Le cancer du sein, parlons-en!” Award, the Canadian Institutes of Health Research for the “CIHR Team in Familial Risks of Breast Cancer” program, the French National Institute of Cancer (INCa) (grants AOR 01 082, 2013-1-BCB-01-ICH-1 and SHS-E-SP 18-015) and the Fondation ARC pour la recherche sur le cancer (grant PJA 20151203365). GEORGETOWN: the Survey, Recruitment and Biospecimen Shared Resource at Georgetown University (NIH/NCI grant P30-CA051008) and the Fisher Center for Hereditary Cancer and Clinical Genomics Research. HCSC: Spanish Ministry of Health PI15/00059, PI16/01292, and CB-161200301 CIBERONC from ISCIII (Spain), partially supported by European Regional Development FEDER funds. HEBCS: Helsinki University Hospital Research Fund, Academy of Finland (266528), the Finnish Cancer Society and the Sigrid Juselius Foundation. HEBON: the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, the Netherlands Organization of Scientific Research grant NWO 91109024, the Pink Ribbon grants 110005 and 2014-187.WO76, the BBMRI grant NWO 184.021.007/CP46 and the Transcan grant JTC 2012 Cancer 12-054. HUNBOCS: Hungarian Research Grants KTIA-OTKA CK-80745 and NKFI_OTKA K-112228. HVH (University Hospital Vall d’Hebron) This work was supported by Spanish Instituto de Salud Carlos III (ISCIII) funding, an initiative of the Spanish Ministry of Economy and Innovation partially supported by European Regional Development FEDER Funds: FIS PI12/02585 and PI15/00355. ICO: The authors would like to particularly acknowledge the support of the Asociación Española Contra el Cáncer (AECC), the Instituto de Salud Carlos III (organismo adscrito al Ministerio de Economía y Competitividad) and “Fondo Europeo de Desarrollo Regional (FEDER), una manera de hacer Europa” (PI10/01422, PI13/00285, PIE13/00022, PI15/00854, PI16/00563, P18/01029, and CIBERONC) and the Institut Català de la Salut and Autonomous Government of Catalonia (2009SGR290, 2014SGR338, 2017SGR449, and PERIS Project MedPerCan), and CERCA program. IHCC: PBZ_KBN_122/P05/2004. ILUH: Icelandic Association “Walking for Breast Cancer Research” and by the Landspitali University Hospital Research Fund. INHERIT: Canadian Institutes of Health Research for the “CIHR Team in Familial Risks of Breast Cancer” program – grant # CRN-87521 and the Ministry of Economic Development, Innovation and Export Trade – grant # PSR-SIIRI-701. IOVHBOCS: Ministero della Salute and “5 × 1000” Istituto Oncologico Veneto grant. IPOBCS: Liga Portuguesa Contra o Cancro. kConFab: The National Breast Cancer Foundation, and previously by the National Health and Medical Research Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. MAYO: NIH grants CA116167, CA192393 and CA176785, an NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), and a grant from the Breast Cancer Research Foundation. MCGILL: Jewish General Hospital Weekend to End Breast Cancer, Quebec Ministry of Economic Development, Innovation and Export Trade. Marc Tischkowitz is supported by the funded by the European Union Seventh Framework Program (2007Y2013)/European Research Council (Grant No. 310018). MSKCC: the Breast Cancer Research Foundation, the Robert and Kate Niehaus Clinical Cancer Genetics Initiative, the Andrew Sabin Research Fund and a Cancer Center Support Grant/Core Grant (P30 CA008748). NCI: the Intramural Research Program of the US National Cancer Institute, NIH, and by support services contracts NO2-CP-11019-50, N02-CP-21013-63 and N02-CP-65504 with Westat, Inc, Rockville, MD. NNPIO: the Russian Foundation for Basic Research (grants 17-54-12007, 17-00-00171 and 18-515-45012). NRG Oncology: U10 CA180868, NRG SDMC grant U10 CA180822, NRG Administrative Office and the NRG Tissue Bank (CA 27469), the NRG Statistical and Data Center (CA 37517) and the Intramural Research Program, NCI. OSUCCG: was funded by the Ohio State University Comprehensive Cancer Center. PBCS: Italian Association of Cancer Research (AIRC) [IG 2013 N.14477] and Tuscany Institute for Tumors (ITT) grant 2014-2015-2016. SMC: the Israeli Cancer Association. SWE-BRCA: the Swedish Cancer Society. UCHICAGO: NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA125183), R01 CA142996, 1U01CA161032 and by the Ralph and Marion Falk Medical Research Trust, the Entertainment Industry Fund National Women’s Cancer Research Alliance and the Breast Cancer research Foundation. UCSF: UCSF Cancer Risk Program and Helen Diller Family Comprehensive Cancer Center. UKFOCR: Cancer Researc h UK. UPENN: National Institutes of Health (NIH) (R01-CA102776 and R01-CA083855; Breast Cancer Research Foundation; Susan G. Komen Foundation for the cure, Basser Research Center for BRCA. UPITT/MWH: Hackers for Hope Pittsburgh. VFCTG: Victorian Cancer Agency, Cancer Australia, National Breast Cancer Foundation. WCP: Dr Karlan is funded by the American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN) and the National Center for Advancing Translational Sciences (NCATS), Grant UL1TR000124.
Published: 2019

35. Association of Childhood and Adolescent Anthropometric Factors, Physical Activity, and Diet with Adult Mammographic Breast Density

Author: Sellers, T. A., Vachon, C. M., Pankratz, V. S., Janney, C. A., Fredericksen, Z., Brandt, K. R., Huang, Y., Couch, F. J., Kushi, L. H., and Cerhan, J. R.
Published: 2007

36. Genetic, functional, and histopathological evaluation of two C-terminal BRCA1 missense variants

Author: Lovelock, P K, Healey, S, Au, W, Sum, E Y M, Tesoriero, A, Wong, E M, Hinson, S, Brinkworth, R, Bekessy, A, Diez, O, Izatt, L, Solomon, E, Jenkins, M, Renard, H, Hopper, J, Waring, P, Tavtigian, S V, Goldgar, D, Lindeman, G J, Visvader, J E, Couch, F J, Henderson, B R, Southey, M, Chenevix-Trench, G, Spurdle, A B, and Brown, M A
Published: 2006

37. CBP truncating mutations in ovarian cancer

Author: Ward, R, Johnson, M, Shridhar, V, van Deursen, J, and Couch, F J
Published: 2005

38. Shared heritability and functional enrichment across six solid cancers

Author: Jiang, X. (Xia), Finucane, H. K. (Hilary K.), Schumacher, F. R. (Fredrick R.), Schmit, S. L. (Stephanie L.), Tyrer, J. P. (Jonathan P.), Han, Y. (Younghun), Michailidou, K. (Kyriaki), Lesseur, C. (Corina), Kuchenbaecker, K. B. (Karoline B.), Dennis, J. (Joe), Conti, D. V. (David V.), Casey, G. (Graham), Gaudet, M. M. (Mia M.), Huyghe, J. R. (Jeroen R.), Albanes, D. (Demetrius), Aldrich, M. C. (Melinda C.), Andrew, A. S. (Angeline S.), Andrulis, I. L. (Irene L.), Anton-Culver, H. (Hoda), Antoniou, A. C. (Antonis C.), Antonenkova, N. N. (Natalia N.), Arnold, S. M. (Susanne M.), Aronson, K. J. (Kristan J.), Arun, B. K. (Banu K.), Bandera, E. V. (Elisa V.), Barkardottir, R. B. (Rosa B.), Barnes, D. R. (Daniel R.), Batra, J. (Jyotsna), Beckmann, M. W. (Matthias W.), Benitez, J. (Javier), Benlloch, S. (Sara), Berchuck, A. (Andrew), Berndt, S. I. (Sonja I.), Bickeboeller, H. (Heike), Bien, S. A. (Stephanie A.), Blomqvist, C. (Carl), Boccia, S. (Stefania), Bogdanova, N. V. (Natalia V.), Bojesen, S. E. (Stig E.), Bolla, M. K. (Manjeet K.), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Brenton, J. D. (James D.), Brook, M. N. (Mark N.), Brunet, J. (Joan), Brunnstrom, H. (Hans), Buchanan, D. D. (Daniel D.), Burwinkel, B. (Barbara), Butzow, R. (Ralf), Cadoni, G. (Gabriella), Caldes, T. (Trinidad), Caligo, M. A. (Maria A.), Campbell, I. (Ian), Campbell, P. T. (Peter T.), Cancel-Tassin, G. (Geraldine), Cannon-Albright, L. (Lisa), Campa, D. (Daniele), Caporaso, N. (Neil), Carvalho, A. L. (Andre L.), Chan, A. T. (Andrew T.), Chang-Claude, J. (Jenny), Chanock, S. J. (Stephen J.), Chen, C. (Chu), Christiani, D. C. (David C.), Claes, K. B. (Kathleen B. M.), Claessens, F. (Frank), Clements, J. (Judith), Collee, J. M. (J. Margriet), Correa, M. C. (Marcia Cruz), Couch, F. J. (Fergus J.), Cox, A. (Angela), Cunningham, J. M. (Julie M.), Cybulski, C. (Cezary), Czene, K. (Kamila), Daly, M. B. (Mary B.), defazio, A. (Anna), Devilee, P. (Peter), Diez, O. (Orland), Gago-Dominguez, M. (Manuela), Donovan, J. L. (Jenny L.), Doerk, T. (Thilo), Duell, E. J. (Eric J.), Dunning, A. M. (Alison M.), Dwek, M. (Miriam), Eccles, D. M. (Diana M.), Edlund, C. K. (Christopher K.), Edwards, D. R. (Digna R. Velez), Ellberg, C. (Carolina), Evans, D. G. (D. Gareth), Fasching, P. A. (Peter A.), Ferris, R. L. (Robert L.), Liloglou, T. (Triantafillos), Figueiredo, J. C. (Jane C.), Fletcher, O. (Olivia), Fortner, R. T. (Renee T.), Fostira, F. (Florentia), Franceschi, S. (Silvia), Friedman, E. (Eitan), Gallinger, S. J. (Steven J.), Ganz, P. A. (Patricia A.), Garber, J. (Judy), Garcia-Saenz, J. A. (Jose A.), Gayther, S. A. (Simon A.), Giles, G. G. (Graham G.), Godwin, A. K. (Andrew K.), Goldberg, M. S. (Mark S.), Goldgar, D. E. (David E.), Goode, E. L. (Ellen L.), Goodman, M. T. (Marc T.), Goodman, G. (Gary), Grankvist, K. (Kjell), Greene, M. H. (Mark H.), Gronberg, H. (Henrik), Gronwald, J. (Jacek), Guenel, P. (Pascal), Hakansson, N. (Niclas), Hall, P. (Per), Hamann, U. (Ute), Hamdy, F. C. (Freddie C.), Hamilton, R. J. (Robert J.), Hampe, J. (Jochen), Haugen, A. (Aage), Heitz, F. (Florian), Herrero, R. (Rolando), Hillemanns, P. (Peter), Hoffmeister, M. (Michael), Hogdall, E. (Estrid), Hong, Y.-C. (Yun-Chul), Hopper, J. L. (John L.), Houlston, R. (Richard), Hulick, P. J. (Peter J.), Hunter, D. J. (David J.), Huntsman, D. G. (David G.), Idos, G. (Gregory), Imyanitov, E. N. (Evgeny N.), Ingles, S. A. (Sue Ann), Isaacs, C. (Claudine), Jakubowska, A. (Anna), James, P. (Paul), Jenkins, M. A. (Mark A.), Johansson, M. (Mattias), Johansson, M. (Mikael), John, E. M. (Esther M.), Joshi, A. D. (Amit D.), Kaneva, R. (Radka), Karlan, B. Y. (Beth Y.), Kelemen, L. E. (Linda E.), Kuhl, T. (Tabea), Khaw, K.-T. (Kay-Tee), Khusnutdinova, E. (Elza), Kibel, A. S. (Adam S.), Kiemeney, L. A. (Lambertus A.), Kim, J. (Jeri), Kjaer, S. K. (Susanne K.), Knight, J. A. (Julia A.), Kogevinas, M. (Manolis), Kote-Jarai, Z. (Zsofia), Koutros, S. (Stella), Kristensen, V. N. (Vessela N.), Kupryjanczyk, J. (Jolanta), Lacko, M. (Martin), Lam, S. (Stephan), Lambrechts, D. (Diether), Landi, M. T. (Maria Teresa), Lazarus, P. (Philip), Le, N. D. (Nhu D.), Lee, E. (Eunjung), Lejbkowicz, F. (Flavio), Lenz, H.-J. (Heinz-Josef), Leslie, G. (Goska), Lessel, D. (Davor), Lester, J. (Jenny), Levine, D. A. (Douglas A.), Li, L. (Li), Li, C. I. (Christopher I.), Lindblom, A. (Annika), Lindor, N. M. (Noralane M.), Liu, G. (Geoffrey), Loupakis, F. (Fotios), Lubinski, J. (Jan), Maehle, L. (Lovise), Maier, C. (Christiane), Mannermaa, A. (Arto), Le Marchand, L. (Loic), Margolin, S. (Sara), May, T. (Taymaa), McGuffog, L. (Lesley), Meindl, A. (Alfons), Middha, P. (Pooja), Miller, A. (Austin), Milne, R. L. (Roger L.), MacInnis, R. J. (Robert J.), Modugno, F. (Francesmary), Montagna, M. (Marco), Moreno, V. (Victor), Moysich, K. B. (Kirsten B.), Mucci, L. (Lorelei), Muir, K. (Kenneth), Mulligan, A. M. (Anna Marie), Nathanson, K. L. (Katherine L.), Neal, D. E. (David E.), Ness, A. R. (Andrew R.), Neuhausen, S. L. (Susan L.), Nevanlinna, H. (Heli), Newcomb, P. A. (Polly A.), Newcomb, L. F. (Lisa F.), Nielsen, F. C. (Finn Cilius), Nikitina-Zake, L. (Liene), Nordestgaard, B. G. (Borge G.), Nussbaum, R. L. (Robert L.), Offit, K. (Kenneth), Olah, E. (Edith), Al Olama, A. A. (Ali Amin), Olopade, O. I. (Olufunmilayo I.), Olshan, A. F. (Andrew F.), Olsson, H. (Hakan), Osorio, A. (Ana), Pandha, H. (Hardev), Park, J. Y. (Jong Y.), Pashayan, N. (Nora), Parsons, M. T. (Michael T.), Pejovic, T. (Tanja), Penney, K. L. (Kathryn L.), Peters, W. H. (Wilbert H. M.), Phelan, C. M. (Catherine M.), Phipps, A. I. (Amanda I.), Plaseska-Karanfilska, D. (Dijana), Pring, M. (Miranda), Prokofyeva, D. (Darya), Radice, P. (Paolo), Stefansson, K. (Kari), Ramus, S. J. (Susan J.), Raskin, L. (Leon), Rennert, G. (Gad), Rennert, H. S. (Hedy S.), van Rensburg, E. J. (Elizabeth J.), Riggan, M. J. (Marjorie J.), Risch, H. A. (Harvey A.), Risch, A. (Angela), Roobol, M. J. (Monique J.), Rosenstein, B. S. (Barry S.), Rossing, M. A. (Mary Anne), De Ruyck, K. (Kim), Saloustros, E. (Emmanouil), Sandler, D. P. (Dale P.), Sawyer, E. J. (Elinor J.), Schabath, M. B. (Matthew B.), Schleutker, J. (Johanna), Schmidt, M. K. (Marjanka K.), Setiawan, V. W. (V. Wendy), Shen, H. (Hongbing), Siegel, E. M. (Erin M.), Sieh, W. (Weiva), Singer, C. F. (Christian F.), Slattery, M. L. (Martha L.), Sorensen, K. D. (Karina Dalsgaard), Southey, M. C. (Melissa C.), Spurdle, A. B. (Amanda B.), Stanford, J. L. (Janet L.), Stevens, V. L. (Victoria L.), Stintzing, S. (Sebastian), Stone, J. (Jennifer), Sundfeldt, K. (Karin), Sutphen, R. (Rebecca), Swerdlow, A. J. (Anthony J.), Tajara, E. H. (Eloiza H.), Tangen, C. M. (Catherine M.), Tardon, A. (Adonina), Taylor, J. A. (Jack A.), Teare, M. D. (M. Dawn), Teixeira, M. R. (Manuel R.), Terry, M. B. (Mary Beth), Terry, K. L. (Kathryn L.), Thibodeau, S. N. (Stephen N.), Thomassen, M. (Mads), Bjorge, L. (Line), Tischkowitz, M. (Marc), Toland, A. E. (Amanda E.), Torres, D. (Diana), Townsend, P. A. (Paul A.), Travis, R. C. (Ruth C.), Tung, N. (Nadine), Tworoger, S. S. (Shelley S.), Ulrich, C. M. (Cornelia M.), Usmani, N. (Nawaid), Vachon, C. M. (Celine M.), Van Nieuwenhuysen, E. (Els), Vega, A. (Ana), Aguado-Barrera, M. E. (Miguel Elias), Wang, Q. (Qin), Webb, P. M. (Penelope M.), Weinberg, C. R. (Clarice R.), Weinstein, S. (Stephanie), Weissler, M. C. (Mark C.), Weitzel, J. N. (Jeffrey N.), West, C. M. (Catharine M. L.), White, E. (Emily), Whittemore, A. S. (Alice S.), Wichmann, H.-E. (H-Erich), Wiklund, F. (Fredrik), Winqvist, R. (Robert), Wolk, A. (Alicja), Woll, P. (Penella), Woods, M. (Michael), Wu, A. H. (Anna H.), Wu, X. (Xifeng), Yannoukakos, D. (Drakoulis), Zheng, W. (Wei), Zienolddiny, S. (Shanbeh), Ziogas, A. (Argyrios), Zorn, K. K. (Kristin K.), Lane, J. M. (Jacqueline M.), Saxena, R. (Richa), Thomas, D. (Duncan), Hung, R. J. (Rayjean J.), Diergaarde, B. (Brenda), Mckay, J. (James), Peters, U. (Ulrike), Hsu, L. (Li), Garcia-Closas, M. (Montserrat), Eeles, R. A. (Rosalind A.), Chenevix-Trench, G. (Georgia), Brennan, P. J. (Paul J.), Haiman, C. A. (Christopher A.), Simard, J. (Jacques), Easton, D. F. (Douglas F.), Gruber, S. B. (Stephen B.), Pharoah, P. D. (Paul D. P.), Price, A. L. (Alkes L.), Pasaniuc, B. (Bogdan), Amos, C. I. (Christopher I.), Kraft, P. (Peter), Lindstrom, S. (Sara), Jiang, X. (Xia), Finucane, H. K. (Hilary K.), Schumacher, F. R. (Fredrick R.), Schmit, S. L. (Stephanie L.), Tyrer, J. P. (Jonathan P.), Han, Y. (Younghun), Michailidou, K. (Kyriaki), Lesseur, C. (Corina), Kuchenbaecker, K. B. (Karoline B.), Dennis, J. (Joe), Conti, D. V. (David V.), Casey, G. (Graham), Gaudet, M. M. (Mia M.), Huyghe, J. R. (Jeroen R.), Albanes, D. (Demetrius), Aldrich, M. C. (Melinda C.), Andrew, A. S. (Angeline S.), Andrulis, I. L. (Irene L.), Anton-Culver, H. (Hoda), Antoniou, A. C. (Antonis C.), Antonenkova, N. N. (Natalia N.), Arnold, S. M. (Susanne M.), Aronson, K. J. (Kristan J.), Arun, B. K. (Banu K.), Bandera, E. V. (Elisa V.), Barkardottir, R. B. (Rosa B.), Barnes, D. R. (Daniel R.), Batra, J. (Jyotsna), Beckmann, M. W. (Matthias W.), Benitez, J. (Javier), Benlloch, S. (Sara), Berchuck, A. (Andrew), Berndt, S. I. (Sonja I.), Bickeboeller, H. (Heike), Bien, S. A. (Stephanie A.), Blomqvist, C. (Carl), Boccia, S. (Stefania), Bogdanova, N. V. (Natalia V.), Bojesen, S. E. (Stig E.), Bolla, M. K. (Manjeet K.), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Brenton, J. D. (James D.), Brook, M. N. (Mark N.), Brunet, J. (Joan), Brunnstrom, H. (Hans), Buchanan, D. D. (Daniel D.), Burwinkel, B. (Barbara), Butzow, R. (Ralf), Cadoni, G. (Gabriella), Caldes, T. (Trinidad), Caligo, M. A. (Maria A.), Campbell, I. (Ian), Campbell, P. T. (Peter T.), Cancel-Tassin, G. (Geraldine), Cannon-Albright, L. (Lisa), Campa, D. (Daniele), Caporaso, N. (Neil), Carvalho, A. L. (Andre L.), Chan, A. T. (Andrew T.), Chang-Claude, J. (Jenny), Chanock, S. J. (Stephen J.), Chen, C. (Chu), Christiani, D. C. (David C.), Claes, K. B. (Kathleen B. M.), Claessens, F. (Frank), Clements, J. (Judith), Collee, J. M. (J. Margriet), Correa, M. C. (Marcia Cruz), Couch, F. J. (Fergus J.), Cox, A. (Angela), Cunningham, J. M. (Julie M.), Cybulski, C. (Cezary), Czene, K. (Kamila), Daly, M. B. (Mary B.), defazio, A. (Anna), Devilee, P. (Peter), Diez, O. (Orland), Gago-Dominguez, M. (Manuela), Donovan, J. L. (Jenny L.), Doerk, T. (Thilo), Duell, E. J. (Eric J.), Dunning, A. M. (Alison M.), Dwek, M. (Miriam), Eccles, D. M. (Diana M.), Edlund, C. K. (Christopher K.), Edwards, D. R. (Digna R. Velez), Ellberg, C. (Carolina), Evans, D. G. (D. Gareth), Fasching, P. A. (Peter A.), Ferris, R. L. (Robert L.), Liloglou, T. (Triantafillos), Figueiredo, J. C. (Jane C.), Fletcher, O. (Olivia), Fortner, R. T. (Renee T.), Fostira, F. (Florentia), Franceschi, S. (Silvia), Friedman, E. (Eitan), Gallinger, S. J. (Steven J.), Ganz, P. A. (Patricia A.), Garber, J. (Judy), Garcia-Saenz, J. A. (Jose A.), Gayther, S. A. (Simon A.), Giles, G. G. (Graham G.), Godwin, A. K. (Andrew K.), Goldberg, M. S. (Mark S.), Goldgar, D. E. (David E.), Goode, E. L. (Ellen L.), Goodman, M. T. (Marc T.), Goodman, G. (Gary), Grankvist, K. (Kjell), Greene, M. H. (Mark H.), Gronberg, H. (Henrik), Gronwald, J. (Jacek), Guenel, P. (Pascal), Hakansson, N. (Niclas), Hall, P. (Per), Hamann, U. (Ute), Hamdy, F. C. (Freddie C.), Hamilton, R. J. (Robert J.), Hampe, J. (Jochen), Haugen, A. (Aage), Heitz, F. (Florian), Herrero, R. (Rolando), Hillemanns, P. (Peter), Hoffmeister, M. (Michael), Hogdall, E. (Estrid), Hong, Y.-C. (Yun-Chul), Hopper, J. L. (John L.), Houlston, R. (Richard), Hulick, P. J. (Peter J.), Hunter, D. J. (David J.), Huntsman, D. G. (David G.), Idos, G. (Gregory), Imyanitov, E. N. (Evgeny N.), Ingles, S. A. (Sue Ann), Isaacs, C. (Claudine), Jakubowska, A. (Anna), James, P. (Paul), Jenkins, M. A. (Mark A.), Johansson, M. (Mattias), Johansson, M. (Mikael), John, E. M. (Esther M.), Joshi, A. D. (Amit D.), Kaneva, R. (Radka), Karlan, B. Y. (Beth Y.), Kelemen, L. E. (Linda E.), Kuhl, T. (Tabea), Khaw, K.-T. (Kay-Tee), Khusnutdinova, E. (Elza), Kibel, A. S. (Adam S.), Kiemeney, L. A. (Lambertus A.), Kim, J. (Jeri), Kjaer, S. K. (Susanne K.), Knight, J. A. (Julia A.), Kogevinas, M. (Manolis), Kote-Jarai, Z. (Zsofia), Koutros, S. (Stella), Kristensen, V. N. (Vessela N.), Kupryjanczyk, J. (Jolanta), Lacko, M. (Martin), Lam, S. (Stephan), Lambrechts, D. (Diether), Landi, M. T. (Maria Teresa), Lazarus, P. (Philip), Le, N. D. (Nhu D.), Lee, E. (Eunjung), Lejbkowicz, F. (Flavio), Lenz, H.-J. (Heinz-Josef), Leslie, G. (Goska), Lessel, D. (Davor), Lester, J. (Jenny), Levine, D. A. (Douglas A.), Li, L. (Li), Li, C. I. (Christopher I.), Lindblom, A. (Annika), Lindor, N. M. (Noralane M.), Liu, G. (Geoffrey), Loupakis, F. (Fotios), Lubinski, J. (Jan), Maehle, L. (Lovise), Maier, C. (Christiane), Mannermaa, A. (Arto), Le Marchand, L. (Loic), Margolin, S. (Sara), May, T. (Taymaa), McGuffog, L. (Lesley), Meindl, A. (Alfons), Middha, P. (Pooja), Miller, A. (Austin), Milne, R. L. (Roger L.), MacInnis, R. J. (Robert J.), Modugno, F. (Francesmary), Montagna, M. (Marco), Moreno, V. (Victor), Moysich, K. B. (Kirsten B.), Mucci, L. (Lorelei), Muir, K. (Kenneth), Mulligan, A. M. (Anna Marie), Nathanson, K. L. (Katherine L.), Neal, D. E. (David E.), Ness, A. R. (Andrew R.), Neuhausen, S. L. (Susan L.), Nevanlinna, H. (Heli), Newcomb, P. A. (Polly A.), Newcomb, L. F. (Lisa F.), Nielsen, F. C. (Finn Cilius), Nikitina-Zake, L. (Liene), Nordestgaard, B. G. (Borge G.), Nussbaum, R. L. (Robert L.), Offit, K. (Kenneth), Olah, E. (Edith), Al Olama, A. A. (Ali Amin), Olopade, O. I. (Olufunmilayo I.), Olshan, A. F. (Andrew F.), Olsson, H. (Hakan), Osorio, A. (Ana), Pandha, H. (Hardev), Park, J. Y. (Jong Y.), Pashayan, N. (Nora), Parsons, M. T. (Michael T.), Pejovic, T. (Tanja), Penney, K. L. (Kathryn L.), Peters, W. H. (Wilbert H. M.), Phelan, C. M. (Catherine M.), Phipps, A. I. (Amanda I.), Plaseska-Karanfilska, D. (Dijana), Pring, M. (Miranda), Prokofyeva, D. (Darya), Radice, P. (Paolo), Stefansson, K. (Kari), Ramus, S. J. (Susan J.), Raskin, L. (Leon), Rennert, G. (Gad), Rennert, H. S. (Hedy S.), van Rensburg, E. J. (Elizabeth J.), Riggan, M. J. (Marjorie J.), Risch, H. A. (Harvey A.), Risch, A. (Angela), Roobol, M. J. (Monique J.), Rosenstein, B. S. (Barry S.), Rossing, M. A. (Mary Anne), De Ruyck, K. (Kim), Saloustros, E. (Emmanouil), Sandler, D. P. (Dale P.), Sawyer, E. J. (Elinor J.), Schabath, M. B. (Matthew B.), Schleutker, J. (Johanna), Schmidt, M. K. (Marjanka K.), Setiawan, V. W. (V. Wendy), Shen, H. (Hongbing), Siegel, E. M. (Erin M.), Sieh, W. (Weiva), Singer, C. F. (Christian F.), Slattery, M. L. (Martha L.), Sorensen, K. D. (Karina Dalsgaard), Southey, M. C. (Melissa C.), Spurdle, A. B. (Amanda B.), Stanford, J. L. (Janet L.), Stevens, V. L. (Victoria L.), Stintzing, S. (Sebastian), Stone, J. (Jennifer), Sundfeldt, K. (Karin), Sutphen, R. (Rebecca), Swerdlow, A. J. (Anthony J.), Tajara, E. H. (Eloiza H.), Tangen, C. M. (Catherine M.), Tardon, A. (Adonina), Taylor, J. A. (Jack A.), Teare, M. D. (M. Dawn), Teixeira, M. R. (Manuel R.), Terry, M. B. (Mary Beth), Terry, K. L. (Kathryn L.), Thibodeau, S. N. (Stephen N.), Thomassen, M. (Mads), Bjorge, L. (Line), Tischkowitz, M. (Marc), Toland, A. E. (Amanda E.), Torres, D. (Diana), Townsend, P. A. (Paul A.), Travis, R. C. (Ruth C.), Tung, N. (Nadine), Tworoger, S. S. (Shelley S.), Ulrich, C. M. (Cornelia M.), Usmani, N. (Nawaid), Vachon, C. M. (Celine M.), Van Nieuwenhuysen, E. (Els), Vega, A. (Ana), Aguado-Barrera, M. E. (Miguel Elias), Wang, Q. (Qin), Webb, P. M. (Penelope M.), Weinberg, C. R. (Clarice R.), Weinstein, S. (Stephanie), Weissler, M. C. (Mark C.), Weitzel, J. N. (Jeffrey N.), West, C. M. (Catharine M. L.), White, E. (Emily), Whittemore, A. S. (Alice S.), Wichmann, H.-E. (H-Erich), Wiklund, F. (Fredrik), Winqvist, R. (Robert), Wolk, A. (Alicja), Woll, P. (Penella), Woods, M. (Michael), Wu, A. H. (Anna H.), Wu, X. (Xifeng), Yannoukakos, D. (Drakoulis), Zheng, W. (Wei), Zienolddiny, S. (Shanbeh), Ziogas, A. (Argyrios), Zorn, K. K. (Kristin K.), Lane, J. M. (Jacqueline M.), Saxena, R. (Richa), Thomas, D. (Duncan), Hung, R. J. (Rayjean J.), Diergaarde, B. (Brenda), Mckay, J. (James), Peters, U. (Ulrike), Hsu, L. (Li), Garcia-Closas, M. (Montserrat), Eeles, R. A. (Rosalind A.), Chenevix-Trench, G. (Georgia), Brennan, P. J. (Paul J.), Haiman, C. A. (Christopher A.), Simard, J. (Jacques), Easton, D. F. (Douglas F.), Gruber, S. B. (Stephen B.), Pharoah, P. D. (Paul D. P.), Price, A. L. (Alkes L.), Pasaniuc, B. (Bogdan), Amos, C. I. (Christopher I.), Kraft, P. (Peter), and Lindstrom, S. (Sara)
Abstract: Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (rg = 0.57, p = 4.6 × 10−8), breast and ovarian cancer (rg = 0.24, p = 7 × 10−5), breast and lung cancer (rg = 0.18, p =1.5 × 10−6) and breast and colorectal cancer (rg = 0.15, p = 1.1 × 10−4). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.
Published: 2019

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

Author: Ferreira, M. A. (Manuel A.), Gamazon, E. R. (Eric R.), Al-Ejeh, F. (Fares), Aittomaki, K. (Kristiina), Andrulis, I. L. (Irene L.), Anton-Culver, H. (Hoda), Arason, A. (Adalgeir), Arndt, V. (Volker), Aronson, K. J. (Kristan J.), Arun, B. K. (Banu K.), Asseryanis, E. (Ella), Azzollini, J. (Jacopo), Balmana, J. (Judith), Barnes, D. R. (Daniel R.), Barrowdale, D. (Daniel), Beckmann, M. W. (Matthias W.), Behrens, S. (Sabine), Benitez, J. (Javier), Bermisheva, M. (Marina), Bialkowska, K. (Katarzyna), Blomqvist, C. (Carl), Bogdanova, N. V. (Natalia, V), Bojesen, S. E. (Stig E.), Bolla, M. K. (Manjeet K.), Borg, A. (Ake), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Broeks, A. (Annegien), Burwinkel, B. (Barbara), Caldes, T. (Trinidad), Caligo, M. A. (Maria A.), Campa, D. (Daniele), Campbell, I. (Ian), Canzian, F. (Federico), Carter, J. (Jonathan), Carter, B. D. (Brian D.), Castelao, J. E. (Jose E.), Chang-Claude, J. (Jenny), Chanock, S. J. (Stephen J.), Christiansen, H. (Hans), Chung, W. K. (Wendy K.), Claes, K. B. (Kathleen B. M.), Clarke, C. L. (Christine L.), Couch, F. J. (Fergus J.), Cox, A. (Angela), Cross, S. S. (Simon S.), Czene, K. (Kamila), Daly, M. B. (Mary B.), de la Hoya, M. (Miguel), Dennis, J. (Joe), Devilee, P. (Peter), Diez, O. (Orland), Doerk, T. (Thilo), Dunning, A. M. (Alison M.), Dwek, M. (Miriam), Eccles, D. M. (Diana M.), Ejlertsen, B. (Bent), Ellberg, C. (Carolina), Engel, C. (Christoph), Eriksson, M. (Mikael), Fasching, P. A. (Peter A.), Fletcher, O. (Olivia), Flyger, H. (Henrik), Friedman, E. (Eitan), Frost, D. (Debra), Gabrielson, M. (Marike), Gago-Dominguez, M. (Manuela), Ganz, P. A. (Patricia A.), Gapstur, S. M. (Susan M.), Garber, J. (Judy), Garcia-Closas, M. (Montserrat), Garcia-Saenz, J. A. (Jose A.), Gaudet, M. M. (Mia M.), Giles, G. G. (Graham G.), Glendon, G. (Gord), Godwin, A. K. (Andrew K.), Goldberg, M. S. (Mark S.), Goldgar, D. E. (David E.), Gonzalez-Neira, A. (Anna), Greene, M. H. (Mark H.), Gronwald, J. (Jacek), Guenel, P. (Pascal), Haiman, C. A. (Christopher A.), Hall, P. (Per), Hamann, U. (Ute), He, W. (Wei), Heyworth, J. (Jane), Hogervorst, F. B. (Frans B. L.), Hollestelle, A. (Antoinette), Hoover, R. N. (Robert N.), Hopper, J. L. (John L.), Hulick, P. J. (Peter J.), Humphreys, K. (Keith), Imyanitov, E. N. (Evgeny N.), Isaacs, C. (Claudine), Jakimovska, M. (Milena), Jakubowska, A. (Anna), James, P. A. (Paul A.), Janavicius, R. (Ramunas), Jankowitz, R. C. (Rachel C.), John, E. M. (Esther M.), Johnson, N. (Nichola), Joseph, V. (Vijai), Karlan, B. Y. (Beth Y.), Khusnutdinova, E. (Elza), Kiiski, J. I. (Johanna, I), Ko, Y.-D. (Yon-Dschun), Jones, M. E. (Michael E.), Konstantopoulou, I. (Irene), Kristensen, V. N. (Vessela N.), Laitman, Y. (Yael), Lambrechts, D. (Diether), Lazaro, C. (Conxi), Leslie, G. (Goska), Lester, J. (Jenny), Lesueur, F. (Fabienne), Lindstrom, S. (Sara), Long, J. (Jirong), Loud, J. T. (Jennifer T.), Lubinski, J. (Jan), Makalic, E. (Enes), Mannermaa, A. (Arto), Manoochehri, M. (Mehdi), Margolin, S. (Sara), Maurer, T. (Tabea), Mavroudis, D. (Dimitrios), McGuffog, L. (Lesley), Meindl, A. (Alfons), Menon, U. (Usha), Michailidou, K. (Kyriaki), Miller, A. (Austin), Montagna, M. (Marco), Moreno, F. (Fernando), Moserle, L. (Lidia), Mulligan, A. M. (Anna Marie), Nathanson, K. L. (Katherine L.), Neuhausen, S. L. (Susan L.), Nevanlinna, H. (Heli), Nevelsteen, I. (Ines), Nielsen, F. C. (Finn C.), Nikitina-Zake, L. (Liene), Nussbaum, R. L. (Robert L.), Offit, K. (Kenneth), Olah, E. (Edith), Olopade, O. I. (Olufunmilayo, I), Olsson, H. (Hakan), Osorio, A. (Ana), Papp, J. (Janos), Park-Simon, T.-W. (Tjoung-Won), Parsons, M. T. (Michael T.), Pedersen, I. S. (Inge Sokilde), Peixoto, A. (Ana), Peterlongo, P. (Paolo), Pharoah, P. D. (Paul D. P.), Plaseska-Karanfilska, D. (Dijana), Poppe, B. (Bruce), Presneau, N. (Nadege), Radice, P. (Paolo), Rantala, J. (Johanna), Rennert, G. (Gad), Risch, H. A. (Harvey A.), Saloustros, E. (Emmanouil), Sanden, K. (Kristin), Sawyer, E. J. (Elinor J.), Schmidt, M. K. (Marjanka K.), Schmutzler, R. K. (Rita K.), Sharma, P. (Priyanka), Shu, X.-O. (Xiao-Ou), Simard, J. (Jacques), Singer, C. F. (Christian F.), Soucy, P. (Penny), Southey, M. C. (Melissa C.), Spinelli, J. J. (John J.), Spurdle, A. B. (Amanda B.), Stone, J. (Jennifer), Swerdlow, A. J. (Anthony J.), Tapper, W. J. (William J.), Taylor, J. A. (Jack A.), Teixeira, M. R. (Manuel R.), Terry, M. B. (Mary Beth), Teule, A. (Alex), Thomassen, M. (Mads), Thoene, K. (Kathrin), Thull, D. L. (Darcy L.), Tischkowitz, M. (Marc), Toland, A. E. (Amanda E.), Torres, D. (Diana), Truong, T. (Therese), Tung, N. (Nadine), Vachon, C. M. (Celine M.), van Asperen, C. J. (Christi J.), van den Ouweland, A. M. (Ans M. W.), van Rensburg, E. J. (Elizabeth J.), Vega, A. (Ana), Viel, A. (Alessandra), Wang, Q. (Qin), Wappenschmidt, B. (Barbara), Weitzel, J. N. (Jeffrey N.), Wendt, C. (Camilla), Winqvist, R. (Robert), Yang, X. R. (Xiaohong R.), Yannoukakos, D. (Drakoulis), Ziogas, A. (Argyrios), Kraft, P. (Peter), Antoniou, A. C. (Antonis C.), Zheng, W. (Wei), Easton, D. F. (Douglas F.), Milne, R. L. (Roger L.), Beesley, J. (Jonathan), Chenevix-Trench, G. (Georgia), Arnold, N. (Norbert), Auber, B. (Bernd), Bogdanova-Markov, N. (Nadja), Borde, J. (Julika), Caliebe, A. (Almuth), Ditsch, N. (Nina), Dworniczak, B. (Bernd), Engert, S. (Stefanie), Faust, U. (Ulrike), Gehrig, A. (Andrea), Hahnen, E. (Eric), Hauke, J. (Jan), Hentschel, J. (Julia), Herold, N. (Natalie), Honisch, E. (Ellen), Just, W. (Walter), Kast, K. (Karin), Larsen, M. (Mirjam), Lemke, J. (Johannes), . (), Niederacher, D. (Dieter), Ott, C.-E. (Claus-Eric), Platzer, K. (Konrad), Pohl-Rescigno, E. (Esther), Ramser, J. (Juliane), Rhiem, K. (Kerstin), Steinemann, D. (Doris), Sutter, C. (Christian), Varon-Mateeva, R. (Raymonda), Wang-Gohrke, S. (Shan), Weber, B. H. (Bernhard H. F.), Prieur, F. (Fabienne), Pujol, P. (Pascal), Sagne, C. (Charlotte), Sevenet, N. (Nicolas), Sobol, H. (Hagay), Sokolowska, J. (Johanna), Stoppa-Lyonnet, D. (Dominique), Venat-Bouvet, L. (Laurence), Adlard, J. (Julian), Ahmed, M. (Munaza), Barwell, J. (Julian), Brady, A. (Angela), Brewer, C. (Carole), Cook, J. (Jackie), Davidson, R. (Rosemarie), Donaldson, A. (Alan), Eason, J. (Jacqueline), Eeles, R. (Ros), Evans, D. G. (D. Gareth), Gregory, H. (Helen), Hanson, H. (Helen), Henderson, A. (Alex), Hodgson, S. (Shirley), Izatt, L. (Louise), Kennedy, M. J. (M. John), Lalloo, F. (Fiona), Miller, C. (Clare), Morrison, P. J. (Patrick J.), Ong, K.-r. (Kai-ren), Perkins, J. (Jo), Porteous, M. E. (Mary E.), Rogers, M. T. (Mark T.), Side, L. E. (Lucy E.), Snape, K. (Katie), Walker, L. (Lisa), Harrington, P. A. (Patricia A.), Heemskerk-Gerritsen, B. A. (Bernadette A. M.), Rookus, M. A. (Matti A.), Seynaeve, C. M. (Caroline M.), van der Baan, F. H. (Frederieke H.), van der Hout, A. H. (Annemieke H.), van der Kolk, L. E. (Lizet E.), van der Luijt, R. B. (Rob B.), van Deurzen, C. H. (Carolien H. M.), van Doorn, H. C. (Helena C.), van Engelen, K. (Klaartje), van Hest, L. (Liselotte), van Os, T. A. (Theo A. M.), Verhoef, S. (Senno), Vogel, M. J. (Maartje J.), Wijnen, J. T. (Juul T.), Miron, A. (Alexander), Kapuscinski, M. (Miroslav), Bane, A. (Anita), Ross, E. (Eric), Buys, S. S. (Saundra S.), Conner, T. A. (Thomas A.), Balleine, R. (Rosemary), Baxter, R. (Robert), Braye, S. (Stephen), Carpenter, J. (Jane), Dahlstrom, J. (Jane), Forbes, J. (John), Lee, S. C. (Soon C.), Marsh, D. (Deborah), Morey, A. (Adrienne), Pathmanathan, N. (Nirmala), Simpson, P. (Peter), Spigelman, A. (Allan), Wilcken, N. (Nicholas), Yip, D. (Desmond), Ferreira, M. A. (Manuel A.), Gamazon, E. R. (Eric R.), Al-Ejeh, F. (Fares), Aittomaki, K. (Kristiina), Andrulis, I. L. (Irene L.), Anton-Culver, H. (Hoda), Arason, A. (Adalgeir), Arndt, V. (Volker), Aronson, K. J. (Kristan J.), Arun, B. K. (Banu K.), Asseryanis, E. (Ella), Azzollini, J. (Jacopo), Balmana, J. (Judith), Barnes, D. R. (Daniel R.), Barrowdale, D. (Daniel), Beckmann, M. W. (Matthias W.), Behrens, S. (Sabine), Benitez, J. (Javier), Bermisheva, M. (Marina), Bialkowska, K. (Katarzyna), Blomqvist, C. (Carl), Bogdanova, N. V. (Natalia, V), Bojesen, S. E. (Stig E.), Bolla, M. K. (Manjeet K.), Borg, A. (Ake), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Broeks, A. (Annegien), Burwinkel, B. (Barbara), Caldes, T. (Trinidad), Caligo, M. A. (Maria A.), Campa, D. (Daniele), Campbell, I. (Ian), Canzian, F. (Federico), Carter, J. (Jonathan), Carter, B. D. (Brian D.), Castelao, J. E. (Jose E.), Chang-Claude, J. (Jenny), Chanock, S. J. (Stephen J.), Christiansen, H. (Hans), Chung, W. K. (Wendy K.), Claes, K. B. (Kathleen B. M.), Clarke, C. L. (Christine L.), Couch, F. J. (Fergus J.), Cox, A. (Angela), Cross, S. S. (Simon S.), Czene, K. (Kamila), Daly, M. B. (Mary B.), de la Hoya, M. (Miguel), Dennis, J. (Joe), Devilee, P. (Peter), Diez, O. (Orland), Doerk, T. (Thilo), Dunning, A. M. (Alison M.), Dwek, M. (Miriam), Eccles, D. M. (Diana M.), Ejlertsen, B. (Bent), Ellberg, C. (Carolina), Engel, C. (Christoph), Eriksson, M. (Mikael), Fasching, P. A. (Peter A.), Fletcher, O. (Olivia), Flyger, H. (Henrik), Friedman, E. (Eitan), Frost, D. (Debra), Gabrielson, M. (Marike), Gago-Dominguez, M. (Manuela), Ganz, P. A. (Patricia A.), Gapstur, S. M. (Susan M.), Garber, J. (Judy), Garcia-Closas, M. (Montserrat), Garcia-Saenz, J. A. (Jose A.), Gaudet, M. M. (Mia M.), Giles, G. G. (Graham G.), Glendon, G. (Gord), Godwin, A. K. (Andrew K.), Goldberg, M. S. (Mark S.), Goldgar, D. E. (David E.), Gonzalez-Neira, A. (Anna), Greene, M. H. (Mark H.), Gronwald, J. (Jacek), Guenel, P. (Pascal), Haiman, C. A. (Christopher A.), Hall, P. (Per), Hamann, U. (Ute), He, W. (Wei), Heyworth, J. (Jane), Hogervorst, F. B. (Frans B. L.), Hollestelle, A. (Antoinette), Hoover, R. N. (Robert N.), Hopper, J. L. (John L.), Hulick, P. J. (Peter J.), Humphreys, K. (Keith), Imyanitov, E. N. (Evgeny N.), Isaacs, C. (Claudine), Jakimovska, M. (Milena), Jakubowska, A. (Anna), James, P. A. (Paul A.), Janavicius, R. (Ramunas), Jankowitz, R. C. (Rachel C.), John, E. M. (Esther M.), Johnson, N. (Nichola), Joseph, V. (Vijai), Karlan, B. Y. (Beth Y.), Khusnutdinova, E. (Elza), Kiiski, J. I. (Johanna, I), Ko, Y.-D. (Yon-Dschun), Jones, M. E. (Michael E.), Konstantopoulou, I. (Irene), Kristensen, V. N. (Vessela N.), Laitman, Y. (Yael), Lambrechts, D. (Diether), Lazaro, C. (Conxi), Leslie, G. (Goska), Lester, J. (Jenny), Lesueur, F. (Fabienne), Lindstrom, S. (Sara), Long, J. (Jirong), Loud, J. T. (Jennifer T.), Lubinski, J. (Jan), Makalic, E. (Enes), Mannermaa, A. (Arto), Manoochehri, M. (Mehdi), Margolin, S. (Sara), Maurer, T. (Tabea), Mavroudis, D. (Dimitrios), McGuffog, L. (Lesley), Meindl, A. (Alfons), Menon, U. (Usha), Michailidou, K. (Kyriaki), Miller, A. (Austin), Montagna, M. (Marco), Moreno, F. (Fernando), Moserle, L. (Lidia), Mulligan, A. M. (Anna Marie), Nathanson, K. L. (Katherine L.), Neuhausen, S. L. (Susan L.), Nevanlinna, H. (Heli), Nevelsteen, I. (Ines), Nielsen, F. C. (Finn C.), Nikitina-Zake, L. (Liene), Nussbaum, R. L. (Robert L.), Offit, K. (Kenneth), Olah, E. (Edith), Olopade, O. I. (Olufunmilayo, I), Olsson, H. (Hakan), Osorio, A. (Ana), Papp, J. (Janos), Park-Simon, T.-W. (Tjoung-Won), Parsons, M. T. (Michael T.), Pedersen, I. S. (Inge Sokilde), Peixoto, A. (Ana), Peterlongo, P. (Paolo), Pharoah, P. D. (Paul D. P.), Plaseska-Karanfilska, D. (Dijana), Poppe, B. (Bruce), Presneau, N. (Nadege), Radice, P. (Paolo), Rantala, J. (Johanna), Rennert, G. (Gad), Risch, H. A. (Harvey A.), Saloustros, E. (Emmanouil), Sanden, K. (Kristin), Sawyer, E. J. (Elinor J.), Schmidt, M. K. (Marjanka K.), Schmutzler, R. K. (Rita K.), Sharma, P. (Priyanka), Shu, X.-O. (Xiao-Ou), Simard, J. (Jacques), Singer, C. F. (Christian F.), Soucy, P. (Penny), Southey, M. C. (Melissa C.), Spinelli, J. J. (John J.), Spurdle, A. B. (Amanda B.), Stone, J. (Jennifer), Swerdlow, A. J. (Anthony J.), Tapper, W. J. (William J.), Taylor, J. A. (Jack A.), Teixeira, M. R. (Manuel R.), Terry, M. B. (Mary Beth), Teule, A. (Alex), Thomassen, M. (Mads), Thoene, K. (Kathrin), Thull, D. L. (Darcy L.), Tischkowitz, M. (Marc), Toland, A. E. (Amanda E.), Torres, D. (Diana), Truong, T. (Therese), Tung, N. (Nadine), Vachon, C. M. (Celine M.), van Asperen, C. J. (Christi J.), van den Ouweland, A. M. (Ans M. W.), van Rensburg, E. J. (Elizabeth J.), Vega, A. (Ana), Viel, A. (Alessandra), Wang, Q. (Qin), Wappenschmidt, B. (Barbara), Weitzel, J. N. (Jeffrey N.), Wendt, C. (Camilla), Winqvist, R. (Robert), Yang, X. R. (Xiaohong R.), Yannoukakos, D. (Drakoulis), Ziogas, A. (Argyrios), Kraft, P. (Peter), Antoniou, A. C. (Antonis C.), Zheng, W. (Wei), Easton, D. F. (Douglas F.), Milne, R. L. (Roger L.), Beesley, J. (Jonathan), Chenevix-Trench, G. (Georgia), Arnold, N. (Norbert), Auber, B. (Bernd), Bogdanova-Markov, N. (Nadja), Borde, J. (Julika), Caliebe, A. (Almuth), Ditsch, N. (Nina), Dworniczak, B. (Bernd), Engert, S. (Stefanie), Faust, U. (Ulrike), Gehrig, A. (Andrea), Hahnen, E. (Eric), Hauke, J. (Jan), Hentschel, J. (Julia), Herold, N. (Natalie), Honisch, E. (Ellen), Just, W. (Walter), Kast, K. (Karin), Larsen, M. (Mirjam), Lemke, J. (Johannes), . (), Niederacher, D. (Dieter), Ott, C.-E. (Claus-Eric), Platzer, K. (Konrad), Pohl-Rescigno, E. (Esther), Ramser, J. (Juliane), Rhiem, K. (Kerstin), Steinemann, D. (Doris), Sutter, C. (Christian), Varon-Mateeva, R. (Raymonda), Wang-Gohrke, S. (Shan), Weber, B. H. (Bernhard H. F.), Prieur, F. (Fabienne), Pujol, P. (Pascal), Sagne, C. (Charlotte), Sevenet, N. (Nicolas), Sobol, H. (Hagay), Sokolowska, J. (Johanna), Stoppa-Lyonnet, D. (Dominique), Venat-Bouvet, L. (Laurence), Adlard, J. (Julian), Ahmed, M. (Munaza), Barwell, J. (Julian), Brady, A. (Angela), Brewer, C. (Carole), Cook, J. (Jackie), Davidson, R. (Rosemarie), Donaldson, A. (Alan), Eason, J. (Jacqueline), Eeles, R. (Ros), Evans, D. G. (D. Gareth), Gregory, H. (Helen), Hanson, H. (Helen), Henderson, A. (Alex), Hodgson, S. (Shirley), Izatt, L. (Louise), Kennedy, M. J. (M. John), Lalloo, F. (Fiona), Miller, C. (Clare), Morrison, P. J. (Patrick J.), Ong, K.-r. (Kai-ren), Perkins, J. (Jo), Porteous, M. E. (Mary E.), Rogers, M. T. (Mark T.), Side, L. E. (Lucy E.), Snape, K. (Katie), Walker, L. (Lisa), Harrington, P. A. (Patricia A.), Heemskerk-Gerritsen, B. A. (Bernadette A. M.), Rookus, M. A. (Matti A.), Seynaeve, C. M. (Caroline M.), van der Baan, F. H. (Frederieke H.), van der Hout, A. H. (Annemieke H.), van der Kolk, L. E. (Lizet E.), van der Luijt, R. B. (Rob B.), van Deurzen, C. H. (Carolien H. M.), van Doorn, H. C. (Helena C.), van Engelen, K. (Klaartje), van Hest, L. (Liselotte), van Os, T. A. (Theo A. M.), Verhoef, S. (Senno), Vogel, M. J. (Maartje J.), Wijnen, J. T. (Juul T.), Miron, A. (Alexander), Kapuscinski, M. (Miroslav), Bane, A. (Anita), Ross, E. (Eric), Buys, S. S. (Saundra S.), Conner, T. A. (Thomas A.), Balleine, R. (Rosemary), Baxter, R. (Robert), Braye, S. (Stephen), Carpenter, J. (Jane), Dahlstrom, J. (Jane), Forbes, J. (John), Lee, S. C. (Soon C.), Marsh, D. (Deborah), Morey, A. (Adrienne), Pathmanathan, N. (Nirmala), Simpson, P. (Peter), Spigelman, A. (Allan), Wilcken, N. (Nicholas), and Yip, D. (Desmond)
Abstract: Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.
Published: 2019

40. Polygenic risk scores for prediction of breast cancer and breast cancer subtypes

Author: Mavaddat, N. (Nasim), Michailidou, K. (Kyriaki), Dennis, J. (Joe), Lush, M. (Michael), Fachal, L. (Laura), Lee, A. (Andrew), Tyrer, J. P. (Jonathan P.), Chen, T.-H. (Ting-Huei), Wang, Q. (Qin), Bolla, M. K. (Manjeet K.), Yang, X. (Xin), Adank, M. A. (Muriel A.), Ahearn, T. (Thomas), Aittomaki, K. (Kristiina), Allen, J. (Jamie), Andrulis, I. L. (Irene L.), Anton-Culver, H. (Hoda), Antonenkova, N. N. (Natalia N.), Arndt, V. (Volker), Aronson, K. J. (Kristan J.), Auer, P. L. (Paul L.), Auvinen, P. (Paivi), Barrdahl, M. (Myrto), Freeman, L. E. (Laura E. Beane), Beckmann, M. W. (Matthias W.), Behrens, S. (Sabine), Benitez, J. (Javier), Bermisheva, M. (Marina), Bernstein, L. (Leslie), Blomqvist, C. (Carl), Bogdanova, N. V. (Natalia, V), Bojesen, S. E. (Stig E.), Bonanni, B. (Bernardo), Borresen-Dale, A.-L. (Anne-Lise), Brauch, H. (Hiltrud), Bremer, M. (Michael), Brenner, H. (Hermann), Brentnall, A. (Adam), Brock, I. W. (Ian W.), Brooks-Wilson, A. (Angela), Brucker, S. Y. (Sara Y.), Bruening, T. (Thomas), Burwinkel, B. (Barbara), Campa, D. (Daniele), Carter, B. D. (Brian D.), Castelao, J. E. (Jose E.), Chanock, S. J. (Stephen J.), Chlebowski, R. (Rowan), Christiansen, H. (Hans), Clarke, C. L. (Christine L.), Collee, J. M. (J. Margriet), Cordina-Duverger, E. (Emilie), Cornelissen, S. (Sten), Couch, F. J. (Fergus J.), Cox, A. (Angela), Cross, S. S. (Simon S.), Czene, K. (Kamila), Daly, M. B. (Mary B.), Devilee, P. (Peter), Doerk, T. (Thilo), dos-Santos-Silva, I. (Isabel), Dumont, M. (Martine), Durcan, L. (Lorraine), Dwek, M. (Miriam), Eccles, D. M. (Diana M.), Ekici, A. B. (Arif B.), Eliassen, A. H. (A. Heather), Ellberg, C. (Carolina), Engel, C. (Christoph), Eriksson, M. (Mikael), Evans, D. G. (D. Gareth), Fasching, P. A. (Peter A.), Figueroa, J. (Jonine), Fletcher, O. (Olivia), Flyger, H. (Henrik), Foersti, A. (Asta), Fritschi, L. (Lin), Gabrielson, M. (Marike), Gago-Dominguez, M. (Manuela), Gapstur, S. M. (Susan M.), Garcia-Saenz, J. A. (Jose A.), Gaudet, M. M. (Mia M.), Georgoulias, V. (Vassilios), Giles, G. G. (Graham G.), Gilyazova, I. R. (Irina R.), Glendon, G. (Gord), Goldberg, M. S. (Mark S.), Goldgar, D. E. (David E.), Gonzalez-Neira, A. (Anna), Alnaes, G. I. (Grethe I. Grenaker), Grip, M. (Mervi), Gronwald, J. (Jacek), Grundy, A. (Anne), Guenel, P. (Pascal), Haeberle, L. (Lothar), Hahnen, E. (Eric), Haiman, C. A. (Christopher A.), Hakansson, N. (Niclas), Hamann, U. (Ute), Hankinson, S. E. (Susan E.), Harkness, E. F. (Elaine F.), Hart, S. N. (Steven N.), He, W. (Wei), Hein, A. (Alexander), Heyworth, J. (Jane), Hillemanns, P. (Peter), Hollestelle, A. (Antoinette), Hooning, M. J. (Maartje J.), Hoover, R. N. (Robert N.), Hopper, J. L. (John L.), Howell, A. (Anthony), Huang, G. (Guanmengqian), Humphreys, K. (Keith), Hunter, D. J. (David J.), Jakimovska, M. (Milena), Jakubowska, A. (Anna), Janni, W. (Wolfgang), John, E. M. (Esther M.), Johnson, N. (Nichola), Jones, M. E. (Michael E.), Jukkola-Vuorinen, A. (Arja), Jung, A. (Audrey), Kaaks, R. (Rudolf), Kaczmarek, K. (Katarzyna), Kataja, V. (Vesa), Keeman, R. (Renske), Kerin, M. J. (Michael J.), Khusnutdinova, E. (Elza), Kiiski, J. I. (Johanna, I), Knight, J. A. (Julia A.), Ko, Y.-D. (Yon-Dschun), Kosma, V.-M. (Veli-Matti), Koutros, S. (Stella), Kristensen, V. N. (Vessela N.), Kruger, U. (Ute), Kuehl, T. (Tabea), Lambrechts, D. (Diether), Le Marchand, L. (Loic), Lee, E. (Eunjung), Lejbkowicz, F. (Flavio), Lilyquist, J. (Jenna), Lindblom, A. (Annika), Lindstrom, S. (Sara), Lissowska, J. (Jolanta), Lo, W.-Y. (Wing-Yee), Loibl, S. (Sibylle), Long, J. (Jirong), Lubinski, J. (Jan), Lux, M. P. (Michael P.), MacInnis, R. J. (Robert J.), Maishman, T. (Tom), Makalic, E. (Enes), Kostovska, I. M. (Ivana Maleva), Mannermaa, A. (Arto), Manoukian, S. (Siranoush), Margolin, S. (Sara), Martens, J. W. (John W. M.), Martinez, M. E. (Maria Elena), Mavroudis, D. (Dimitrios), McLean, C. (Catriona), Meindl, A. (Alfons), Menon, U. (Usha), Middha, P. (Pooja), Miller, N. (Nicola), Moreno, F. (Fernando), Mulligan, A. M. (Anna Marie), Mulot, C. (Claire), Munoz-Garzon, V. M. (Victor M.), Neuhausen, S. L. (Susan L.), Nevanlinna, H. (Heli), Neven, P. (Patrick), Newman, W. G. (William G.), Nielsen, S. F. (Sune F.), Nordestgaard, B. G. (Borge G.), Norman, A. (Aaron), Offit, K. (Kenneth), Olson, J. E. (Janet E.), Olsson, H. (Hakan), Orr, N. (Nick), Pankratz, V. S. (V. Shane), Park-Simon, T.-W. (Tjoung-Won), Perez, J. I. (Jose I. A.), Perez-Barrios, C. (Clara), Peterlongo, P. (Paolo), Peto, J. (Julian), Pinchev, M. (Mila), Plaseska-Karanfilska, D. (Dijana), Polley, E. C. (Eric C.), Prentice, R. (Ross), Presneau, N. (Nadege), Prokofyeva, D. (Darya), Purrington, K. (Kristen), Pylkäs, K. (Katri), Rack, B. (Brigitte), Radice, P. (Paolo), Rau-Murthy, R. (Rohini), Rennert, G. (Gad), Rennert, H. S. (Hedy S.), Rhenius, V. (Valerie), Robson, M. (Mark), Romero, A. (Atocha), Ruddy, K. J. (Kathryn J.), Ruebner, M. (Matthias), Saloustros, E. (Emmanouil), Sandler, D. P. (Dale P.), Sawyer, E. J. (Elinor J.), Schmidt, D. F. (Daniel F.), Schmutzler, R. K. (Rita K.), Schneeweiss, A. (Andreas), Schoemaker, M. J. (Minouk J.), Schumacher, F. (Fredrick), Schuermann, P. (Peter), Schwentner, L. (Lukas), Scott, C. (Christopher), Scott, R. J. (Rodney J.), Seynaeve, C. (Caroline), Shah, M. (Mitul), Sherman, M. E. (Mark E.), Shrubsole, M. J. (Martha J.), Shu, X.-O. (Xiao-Ou), Slager, S. (Susan), Smeets, A. (Ann), Sohn, C. (Christof), Soucy, P. (Penny), Southey, M. C. (Melissa C.), Spinelli, J. J. (John J.), Stegmaier, C. (Christa), Stone, J. (Jennifer), 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), Thoene, K. (Kathrin), Tollenaar, R. A. (Rob A. E. M.), Tomlinson, I. (Ian), Truong, T. (Therese), Tzardi, M. (Maria), Ulmer, H.-U. (Hans-Ulrich), Untch, M. (Michael), Vachon, C. M. (Celine M.), van Veen, E. M. (Elke M.), Vijai, J. (Joseph), Weinberg, C. R. (Clarice R.), Wendt, C. (Camilla), Whittemore, A. S. (Alice S.), Wildiers, H. (Hans), Willett, W. (Walter), Winqvist, R. (Robert), Wolk, A. (Alicja), Yang, X. R. (Xiaohong R.), Yannoukakos, D. (Drakoulis), Zhang, Y. (Yan), Zheng, W. (Wei), Ziogas, A. (Argyrios), Clarke, C. (Christine), Balleine, R. (Rosemary), Baxter, R. (Robert), Braye, S. (Stephen), Carpenter, J. (Jane), Dahlstrom, J. (Jane), Forbes, J. (John), Lee, C. S. (C. Soon), Marsh, D. (Deborah), Morey, A. (Adrienne), Pathmanathan, N. (Nirmala), Scott, R. (Rodney), Simpson, P. (Peter), Spigelman, A. (Allan), Wilcken, N. (Nicholas), Yip, D. (Desmond), Zeps, N. (Nikolajs), Sexton, A. (Adrienne), Dobrovic, A. (Alex), Christian, A. (Alice), Trainer, A. (Alison), Fellows, A. (Andrew), Shelling, A. (Andrew), De Fazio, A. (Anna), Blackburn, A. (Anneke), Crook, A. (Ashley), Meiser, B. (Bettina), Patterson, B. (Briony), Clarke, C. (Christobel), Saunders, C. (Christobel), Hunt, C. (Clare), Scott, C. (Clare), Amor, D. (David), Ortega, D. G. (David Gallego), Marsh, D. (Deb), Edkins, E. (Edward), Salisbury, E. (Elizabeth), Haan, E. (Eric), Macrea, F. (Finlay), Farshid, G. (Gelareh), Lindeman, G. (Geoff), Trench, G. (Georgia), Mann, G. (Graham), Giles, G. (Graham), Gill, G. (Grantley), Thorne, H. (Heather), Campbell, I. (Ian), Hickie, I. (Ian), Caldon, L. (Liz), Winship, I. (Ingrid), Cui, J. (James), Flanagan, J. (James), Kollias, J. (James), Visvader, J. (Jane), Taylor, J. (Jessica), Burke, J. (Jo), Saunus, J. (Jodi), Forbs, J. (John), Hopper, J. (John), Beesley, J. (Jonathan), Kirk, J. (Judy), French, J. (Juliet), Tucker, K. (Kathy), Wu, K. (Kathy), Phillips, K. (Kelly), Forrest, L. (Laura), Lipton, L. (Lara), Andrews, L. (Leslie), Lobb, L. (Lizz), Walker, L. (Logan), Kentwell, M. (Maira), Spurdle, M. (Mandy), Cummings, M. (Margaret), Gleeson, M. (Margaret), Harris, M. (Marion), Jenkins, M. (Mark), Young, M. A. (Mary Anne), Delatycki, M. (Martin), Wallis, M. (Mathew), Burgess, M. (Matthew), Brown, M. (Melissa), Southey, M. (Melissa), Bogwitz, M. (Michael), Field, M. (Michael), Friedlander, M. (Michael), Gattas, M. (Michael), Saleh, M. (Mona), Aghmesheh, M. (Morteza), Hayward, N. (Nick), Pachter, N. (Nick), Cohen, P. (Paul), Duijf, P. (Pascal), James, P. (Paul), Simpson, P. (Pete), Fong, P. (Peter), Butow, P. (Phyllis), Williams, R. (Rachael), Kefford, R. (Rick), Simard, J. (Jacques), Balleine, R.-M. (Rose-Mary), Dawson, S.-J. (Sarah-Jane), Lok, S. (Sheau), O'connell, S. (Shona), Greening, S. (Sian), Nightingale, S. (Sophie), Edwards, S. (Stacey), Fox, S. (Stephen), McLachlan, S.-A. (Sue-Anne), Lakhani, S. (Sunil), Dudding, T. (Tracy), Antill, Y. (Yoland), Sahlberg, K. K. (Kristine K.), Ottestad, L. (Lars), Karesen, R. (Rolf), Schlichting, E. (Ellen), Holmen, M. M. (Marit Muri), Sauer, T. (Toril), Haakensen, V. (Vilde), Engebraten, O. (Olav), Naume, B. (Bjorn), Fossa, A. (Alexander), Kiserud, C. E. (Cecile E.), Reinertsen, K. V. (Kristin, V), Helland, A. (Aslaug), Riis, M. (Margit), Geisler, J. (Juergen), Dunning, A. M. (Alison M.), Thompson, D. J. (Deborah J.), Chenevix-Trench, G. (Georgia), Chang-Claude, J. (Jenny), Schmidt, M. K. (Marjanka K.), Hall, P. (Per), Milne, R. L. (Roger L.), Pharoah, P. D. (Paul D. P.), Antoniou, A. C. (Antonis C.), Chatterjee, N. (Nilanjan), Kraft, P. (Peter), Garcia-Closas, M. (Montserrat), Easton, D. F. (Douglas F.), Mavaddat, N. (Nasim), Michailidou, K. (Kyriaki), Dennis, J. (Joe), Lush, M. (Michael), Fachal, L. (Laura), Lee, A. (Andrew), Tyrer, J. P. (Jonathan P.), Chen, T.-H. (Ting-Huei), Wang, Q. (Qin), Bolla, M. K. (Manjeet K.), Yang, X. (Xin), Adank, M. A. (Muriel A.), Ahearn, T. (Thomas), Aittomaki, K. (Kristiina), Allen, J. (Jamie), Andrulis, I. L. (Irene L.), Anton-Culver, H. (Hoda), Antonenkova, N. N. (Natalia N.), Arndt, V. (Volker), Aronson, K. J. (Kristan J.), Auer, P. L. (Paul L.), Auvinen, P. (Paivi), Barrdahl, M. (Myrto), Freeman, L. E. (Laura E. Beane), Beckmann, M. W. (Matthias W.), Behrens, S. (Sabine), Benitez, J. (Javier), Bermisheva, M. (Marina), Bernstein, L. (Leslie), Blomqvist, C. (Carl), Bogdanova, N. V. (Natalia, V), Bojesen, S. E. (Stig E.), Bonanni, B. (Bernardo), Borresen-Dale, A.-L. (Anne-Lise), Brauch, H. (Hiltrud), Bremer, M. (Michael), Brenner, H. (Hermann), Brentnall, A. (Adam), Brock, I. W. (Ian W.), Brooks-Wilson, A. (Angela), Brucker, S. Y. (Sara Y.), Bruening, T. (Thomas), Burwinkel, B. (Barbara), Campa, D. (Daniele), Carter, B. D. (Brian D.), Castelao, J. E. (Jose E.), Chanock, S. J. (Stephen J.), Chlebowski, R. (Rowan), Christiansen, H. (Hans), Clarke, C. L. (Christine L.), Collee, J. M. (J. Margriet), Cordina-Duverger, E. (Emilie), Cornelissen, S. (Sten), Couch, F. J. (Fergus J.), Cox, A. (Angela), Cross, S. S. (Simon S.), Czene, K. (Kamila), Daly, M. B. (Mary B.), Devilee, P. (Peter), Doerk, T. (Thilo), dos-Santos-Silva, I. (Isabel), Dumont, M. (Martine), Durcan, L. (Lorraine), Dwek, M. (Miriam), Eccles, D. M. (Diana M.), Ekici, A. B. (Arif B.), Eliassen, A. H. (A. Heather), Ellberg, C. (Carolina), Engel, C. (Christoph), Eriksson, M. (Mikael), Evans, D. G. (D. Gareth), Fasching, P. A. (Peter A.), Figueroa, J. (Jonine), Fletcher, O. (Olivia), Flyger, H. (Henrik), Foersti, A. (Asta), Fritschi, L. (Lin), Gabrielson, M. (Marike), Gago-Dominguez, M. (Manuela), Gapstur, S. M. (Susan M.), Garcia-Saenz, J. A. (Jose A.), Gaudet, M. M. (Mia M.), Georgoulias, V. (Vassilios), Giles, G. G. (Graham G.), Gilyazova, I. R. (Irina R.), Glendon, G. (Gord), Goldberg, M. S. (Mark S.), Goldgar, D. E. (David E.), Gonzalez-Neira, A. (Anna), Alnaes, G. I. (Grethe I. Grenaker), Grip, M. (Mervi), Gronwald, J. (Jacek), Grundy, A. (Anne), Guenel, P. (Pascal), Haeberle, L. (Lothar), Hahnen, E. (Eric), Haiman, C. A. (Christopher A.), Hakansson, N. (Niclas), Hamann, U. (Ute), Hankinson, S. E. (Susan E.), Harkness, E. F. (Elaine F.), Hart, S. N. (Steven N.), He, W. (Wei), Hein, A. (Alexander), Heyworth, J. (Jane), Hillemanns, P. (Peter), Hollestelle, A. (Antoinette), Hooning, M. J. (Maartje J.), Hoover, R. N. (Robert N.), Hopper, J. L. (John L.), Howell, A. (Anthony), Huang, G. (Guanmengqian), Humphreys, K. (Keith), Hunter, D. J. (David J.), Jakimovska, M. (Milena), Jakubowska, A. (Anna), Janni, W. (Wolfgang), John, E. M. (Esther M.), Johnson, N. (Nichola), Jones, M. E. (Michael E.), Jukkola-Vuorinen, A. (Arja), Jung, A. (Audrey), Kaaks, R. (Rudolf), Kaczmarek, K. (Katarzyna), Kataja, V. (Vesa), Keeman, R. (Renske), Kerin, M. J. (Michael J.), Khusnutdinova, E. (Elza), Kiiski, J. I. (Johanna, I), Knight, J. A. (Julia A.), Ko, Y.-D. (Yon-Dschun), Kosma, V.-M. (Veli-Matti), Koutros, S. (Stella), Kristensen, V. N. (Vessela N.), Kruger, U. (Ute), Kuehl, T. (Tabea), Lambrechts, D. (Diether), Le Marchand, L. (Loic), Lee, E. (Eunjung), Lejbkowicz, F. (Flavio), Lilyquist, J. (Jenna), Lindblom, A. (Annika), Lindstrom, S. (Sara), Lissowska, J. (Jolanta), Lo, W.-Y. (Wing-Yee), Loibl, S. (Sibylle), Long, J. (Jirong), Lubinski, J. (Jan), Lux, M. P. (Michael P.), MacInnis, R. J. (Robert J.), Maishman, T. (Tom), Makalic, E. (Enes), Kostovska, I. M. (Ivana Maleva), Mannermaa, A. (Arto), Manoukian, S. (Siranoush), Margolin, S. (Sara), Martens, J. W. (John W. M.), Martinez, M. E. (Maria Elena), Mavroudis, D. (Dimitrios), McLean, C. (Catriona), Meindl, A. (Alfons), Menon, U. (Usha), Middha, P. (Pooja), Miller, N. (Nicola), Moreno, F. (Fernando), Mulligan, A. M. (Anna Marie), Mulot, C. (Claire), Munoz-Garzon, V. M. (Victor M.), Neuhausen, S. L. (Susan L.), Nevanlinna, H. (Heli), Neven, P. (Patrick), Newman, W. G. (William G.), Nielsen, S. F. (Sune F.), Nordestgaard, B. G. (Borge G.), Norman, A. (Aaron), Offit, K. (Kenneth), Olson, J. E. (Janet E.), Olsson, H. (Hakan), Orr, N. (Nick), Pankratz, V. S. (V. Shane), Park-Simon, T.-W. (Tjoung-Won), Perez, J. I. (Jose I. A.), Perez-Barrios, C. (Clara), Peterlongo, P. (Paolo), Peto, J. (Julian), Pinchev, M. (Mila), Plaseska-Karanfilska, D. (Dijana), Polley, E. C. (Eric C.), Prentice, R. (Ross), Presneau, N. (Nadege), Prokofyeva, D. (Darya), Purrington, K. (Kristen), Pylkäs, K. (Katri), Rack, B. (Brigitte), Radice, P. (Paolo), Rau-Murthy, R. (Rohini), Rennert, G. (Gad), Rennert, H. S. (Hedy S.), Rhenius, V. (Valerie), Robson, M. (Mark), Romero, A. (Atocha), Ruddy, K. J. (Kathryn J.), Ruebner, M. (Matthias), Saloustros, E. (Emmanouil), Sandler, D. P. (Dale P.), Sawyer, E. J. (Elinor J.), Schmidt, D. F. (Daniel F.), Schmutzler, R. K. (Rita K.), Schneeweiss, A. (Andreas), Schoemaker, M. J. (Minouk J.), Schumacher, F. (Fredrick), Schuermann, P. (Peter), Schwentner, L. (Lukas), Scott, C. (Christopher), Scott, R. J. (Rodney J.), Seynaeve, C. (Caroline), Shah, M. (Mitul), Sherman, M. E. (Mark E.), Shrubsole, M. J. (Martha J.), Shu, X.-O. (Xiao-Ou), Slager, S. (Susan), Smeets, A. (Ann), Sohn, C. (Christof), Soucy, P. (Penny), Southey, M. C. (Melissa C.), Spinelli, J. J. (John J.), Stegmaier, C. (Christa), Stone, J. (Jennifer), 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), Thoene, K. (Kathrin), Tollenaar, R. A. (Rob A. E. M.), Tomlinson, I. (Ian), Truong, T. (Therese), Tzardi, M. (Maria), Ulmer, H.-U. (Hans-Ulrich), Untch, M. (Michael), Vachon, C. M. (Celine M.), van Veen, E. M. (Elke M.), Vijai, J. (Joseph), Weinberg, C. R. (Clarice R.), Wendt, C. (Camilla), Whittemore, A. S. (Alice S.), Wildiers, H. (Hans), Willett, W. (Walter), Winqvist, R. (Robert), Wolk, A. (Alicja), Yang, X. R. (Xiaohong R.), Yannoukakos, D. (Drakoulis), Zhang, Y. (Yan), Zheng, W. (Wei), Ziogas, A. (Argyrios), Clarke, C. (Christine), Balleine, R. (Rosemary), Baxter, R. (Robert), Braye, S. (Stephen), Carpenter, J. (Jane), Dahlstrom, J. (Jane), Forbes, J. (John), Lee, C. S. (C. Soon), Marsh, D. (Deborah), Morey, A. (Adrienne), Pathmanathan, N. (Nirmala), Scott, R. (Rodney), Simpson, P. (Peter), Spigelman, A. (Allan), Wilcken, N. (Nicholas), Yip, D. (Desmond), Zeps, N. (Nikolajs), Sexton, A. (Adrienne), Dobrovic, A. (Alex), Christian, A. (Alice), Trainer, A. (Alison), Fellows, A. (Andrew), Shelling, A. (Andrew), De Fazio, A. (Anna), Blackburn, A. (Anneke), Crook, A. (Ashley), Meiser, B. (Bettina), Patterson, B. (Briony), Clarke, C. (Christobel), Saunders, C. (Christobel), Hunt, C. (Clare), Scott, C. (Clare), Amor, D. (David), Ortega, D. G. (David Gallego), Marsh, D. (Deb), Edkins, E. (Edward), Salisbury, E. (Elizabeth), Haan, E. (Eric), Macrea, F. (Finlay), Farshid, G. (Gelareh), Lindeman, G. (Geoff), Trench, G. (Georgia), Mann, G. (Graham), Giles, G. (Graham), Gill, G. (Grantley), Thorne, H. (Heather), Campbell, I. (Ian), Hickie, I. (Ian), Caldon, L. (Liz), Winship, I. (Ingrid), Cui, J. (James), Flanagan, J. (James), Kollias, J. (James), Visvader, J. (Jane), Taylor, J. (Jessica), Burke, J. (Jo), Saunus, J. (Jodi), Forbs, J. (John), Hopper, J. (John), Beesley, J. (Jonathan), Kirk, J. (Judy), French, J. (Juliet), Tucker, K. (Kathy), Wu, K. (Kathy), Phillips, K. (Kelly), Forrest, L. (Laura), Lipton, L. (Lara), Andrews, L. (Leslie), Lobb, L. (Lizz), Walker, L. (Logan), Kentwell, M. (Maira), Spurdle, M. (Mandy), Cummings, M. (Margaret), Gleeson, M. (Margaret), Harris, M. (Marion), Jenkins, M. (Mark), Young, M. A. (Mary Anne), Delatycki, M. (Martin), Wallis, M. (Mathew), Burgess, M. (Matthew), Brown, M. (Melissa), Southey, M. (Melissa), Bogwitz, M. (Michael), Field, M. (Michael), Friedlander, M. (Michael), Gattas, M. (Michael), Saleh, M. (Mona), Aghmesheh, M. (Morteza), Hayward, N. (Nick), Pachter, N. (Nick), Cohen, P. (Paul), Duijf, P. (Pascal), James, P. (Paul), Simpson, P. (Pete), Fong, P. (Peter), Butow, P. (Phyllis), Williams, R. (Rachael), Kefford, R. (Rick), Simard, J. (Jacques), Balleine, R.-M. (Rose-Mary), Dawson, S.-J. (Sarah-Jane), Lok, S. (Sheau), O'connell, S. (Shona), Greening, S. (Sian), Nightingale, S. (Sophie), Edwards, S. (Stacey), Fox, S. (Stephen), McLachlan, S.-A. (Sue-Anne), Lakhani, S. (Sunil), Dudding, T. (Tracy), Antill, Y. (Yoland), Sahlberg, K. K. (Kristine K.), Ottestad, L. (Lars), Karesen, R. (Rolf), Schlichting, E. (Ellen), Holmen, M. M. (Marit Muri), Sauer, T. (Toril), Haakensen, V. (Vilde), Engebraten, O. (Olav), Naume, B. (Bjorn), Fossa, A. (Alexander), Kiserud, C. E. (Cecile E.), Reinertsen, K. V. (Kristin, V), Helland, A. (Aslaug), Riis, M. (Margit), Geisler, J. (Juergen), Dunning, A. M. (Alison M.), Thompson, D. J. (Deborah J.), Chenevix-Trench, G. (Georgia), Chang-Claude, J. (Jenny), Schmidt, M. K. (Marjanka K.), Hall, P. (Per), Milne, R. L. (Roger L.), Pharoah, P. D. (Paul D. P.), Antoniou, A. C. (Antonis C.), Chatterjee, N. (Nilanjan), Kraft, P. (Peter), Garcia-Closas, M. (Montserrat), and Easton, D. F. (Douglas F.)
Abstract: Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets. Samples were genotyped using genome-wide arrays, and single-nucleotide polymorphisms (SNPs) were selected by stepwise regression or lasso penalized regression. The best performing PRSs were validated in an independent test set comprising 11,428 case subjects and 18,323 control subjects from 10 prospective studies and 190,040 women from UK Biobank (3,215 incident breast cancers). For the best PRSs (313 SNPs), the odds ratio for overall disease per 1 standard deviation in ten prospective studies was 1.61 (95%CI: 1.57–1.65) with area under receiver-operator curve (AUC) = 0.630 (95%CI: 0.628–0.651). The lifetime risk of overall breast cancer in the top centile of the PRSs was 32.6%. Compared with women in the middle quintile, those in the highest 1% of risk had 4.37- and 2.78-fold risks, and those in the lowest 1% of risk had 0.16- and 0.27-fold risks, of developing ER-positive and ER-negative disease, respectively. Goodness-of-fit tests indicated that this PRS was well calibrated and predicts disease risk accurately in the tails of the distribution. This PRS is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs.
Published: 2019

41. Oophorectomy and risk of contralateral breast cancer among BRCA1 and BRCA2 mutation carriers

Author: Kotsopoulos, J, Lubinski, J, Lynch, H, Tung, N, Armel, S, Senter, L, Singer, C, Fruscio, R, Couch, F, Weitzel, J, Karlan, B, Foulkes, W, Moller, P, Eisen, A, Ainsworth, P, Neuhausen, S, Olopade, O, Sun, P, Gronwald, J, Narod, S, Lynch, HT, Singer, CF, Weitzel, JN, Foulkes, WD, Neuhausen, SL, Narod, SA, Kotsopoulos, J, Lubinski, J, Lynch, H, Tung, N, Armel, S, Senter, L, Singer, C, Fruscio, R, Couch, F, Weitzel, J, Karlan, B, Foulkes, W, Moller, P, Eisen, A, Ainsworth, P, Neuhausen, S, Olopade, O, Sun, P, Gronwald, J, Narod, S, Lynch, HT, Singer, CF, Weitzel, JN, Foulkes, WD, Neuhausen, SL, and Narod, SA
Abstract: Purpose: Following a diagnosis of breast cancer, BRCA mutation carriers face an increased risk of developing a second (contralateral) cancer in the unaffected breast. It is important to identify predictors of contralateral cancer in order to make informed decisions about bilateral mastectomy. The impact of bilateral salpingo-oophorectomy (i.e., oophorectomy) on the risk of developing contralateral breast cancer is unclear. Thus, we conducted a prospective study of the relationship between oophorectomy and the risk of contralateral breast cancer in 1781 BRCA1 and 503 BRCA2 mutation carriers with breast cancer. Methods: Women were followed from the date of diagnosis of their first breast cancer until the date of diagnosis of a contralateral breast cancer, bilateral mastectomy, date of death, or date of last follow-up. Cox proportional hazards regression was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) of contralateral breast cancer associated with oophorectomy. Oophorectomy was included as a time-dependent covariate. We performed a left-censored analysis for those women who reported a primary breast cancer prior to study entry (i.e., from completion of baseline questionnaire). Results: After an average of 9.8 years of follow-up, there were 179 (7.8%) contralateral breast cancers diagnosed. Oophorectomy was not associated with the risk of developing a second breast cancer (HR 0.92; 95% CI 0.68–1.25). The relationship did not vary by BRCA mutation type or by age at diagnosis of the first breast cancer. There was some evidence for a decreased risk of contralateral breast cancer among women with an ER-positive primary breast cancer, but this was based on a small number of events (n = 240). Conclusion: Overall, our findings suggest that oophorectomy has little impact on the risk of contralateral breast cancer
Published: 2019

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

Author: Jiang, X., Finucane, H. K., Schumacher, F. R., Schmit, S. L., Tyrer, J. P., Han, Y., Michailidou, K., Lesseur, C., Kuchenbaecker, K. B., Dennis, J., Conti, D. V., Casey, G., Gaudet, M. M., Huyghe, J. R., Albanes, D., Aldrich, M. C., Andrew, A. S., Andrulis, I. L., Anton-Culver, H., Antoniou, A. C., Antonenkova, N. N., Arnold, S. M., Aronson, K. J., Arun, B. K., Bandera, E. V., Barkardottir, R. B., Barnes, D. R., Batra, J., Beckmann, M. W., Benitez, J., Benlloch, S., Berchuck, A., Berndt, S. I., Bickeboller, H., Bien, S. A., Blomqvist, C., Boccia, S., Bogdanova, N. V., Bojesen, S. E., Bolla, M. K., Brauch, H., Brenner, H., Brenton, J. D., Brook, M. N., Brunet, J., Brunnstrom, H., Buchanan, D. D., Burwinkel, B., Butzow, R., Cadoni, G., Caldes, T., Caligo, M. A., Campbell, I., Campbell, P. T., Cancel-Tassin, G., Cannon-Albright, L., Campa, D., Caporaso, N., Carvalho, A. L., Chan, A. T., Chang-Claude, J., Chanock, S. J., Chen, Chen, Christiani, D. C., Claes, K. B. M., Claessens, F., Clements, J., Collee, J. M., Correa, M. C., Couch, F. J., Cox, A., Cunningham, J. M., Cybulski, C., Czene, K., Daly, M. B., deFazio, A., Devilee, P., Diez, O., Gago-Dominguez, M., Donovan, J. L., Dork, T., Duell, E. J., Dunning, A. M., Dwek, M., Eccles, D. M., Edlund, C. K., Edwards, D. R. V., Ellberg, C., Evans, D. G., Fasching, P. A., Ferris, R. L., Liloglou, T., Figueiredo, J. C., Fletcher, O., Fortner, R. T., Fostira, F., Franceschi, S., Friedman, E., Gallinger, S. J., Ganz, P. A., Garber, J., Garcia-Saenz, J. A., Gayther, S. A., Giles, G. G., Godwin, A. K., Goldberg, M. S., Goldgar, D. E., Goode, E. L., Goodman, M. T., Goodman, G., Grankvist, K., Greene, M. H., Gronberg, H., Gronwald, J., Guenel, P., Hakansson, N., Hall, P., Hamann, U., Hamdy, F. C., Hamilton, R. J., Hampe, J., Haugen, A., Heitz, F., Herrero, R., Hillemanns, P., Hoffmeister, M., Hogdall, E., Hong, Y. -C., Hopper, J. L., Houlston, R., Hulick, P. J., Hunter, D. J., Huntsman, D. G., Idos, G., Imyanitov, E. N., Ingles, S. A., Isaacs, C., Jakubowska, A., James, P., Jenkins, M. A., Johansson, M., John, E. M., Joshi, A. D., Kaneva, R., Karlan, B. Y., Kelemen, L. E., Kuhl, T., Khaw, K. -T., Khusnutdinova, E., Kibel, A. S., Kiemeney, L. A., Kim, J., Kjaer, S. K., Knight, J. A., Kogevinas, M., Kote-Jarai, Z., Koutros, S., Kristensen, V. N., Kupryjanczyk, J., Lacko, M., Lam, S., Lambrechts, D., Landi, M. T., Lazarus, P., Le, N. D., Lee, E., Lejbkowicz, F., Lenz, H. -J., Leslie, G., Lessel, D., Lester, J., Levine, D. A., Li, L., Li, C. I., Lindblom, A., Lindor, N. M., Liu, G., Loupakis, F., Lubinski, J., Maehle, L., Maier, C., Mannermaa, A., Marchand, L. L., Margolin, S., May, T., McGuffog, L., Meindl, A., Middha, P., Miller, A., Milne, R. L., MacInnis, R. J., Modugno, F., Montagna, M., Moreno, V., Moysich, K. B., Mucci, L., Muir, K., Mulligan, A. M., Nathanson, K. L., Neal, D. E., Ness, A. R., Neuhausen, S. L., Nevanlinna, H., Newcomb, P. A., Newcomb, L. F., Nielsen, F. C., Nikitina-Zake, L., Nordestgaard, B. G., Nussbaum, R. L., Offit, K., Olah, E., Olama, A. A. A., Olopade, O. I., Olshan, A. F., Olsson, H., Osorio, A., Pandha, H., Park, J. Y., Pashayan, N., Parsons, M. T., Pejovic, T., Penney, K. L., Peters, W. H. M., Phelan, C. M., Phipps, A. I., Plaseska-Karanfilska, D., Pring, M., Prokofyeva, D., Radice, P., Stefansson, K., Ramus, S. J., Raskin, L., Rennert, G., Rennert, H. S., van Rensburg, E. J., Riggan, M. J., Risch, H. A., Risch, A., Roobol, M. J., Rosenstein, B. S., Rossing, M. A., De Ruyck, K., Saloustros, E., Sandler, D. P., Sawyer, E. J., Schabath, M. B., Schleutker, J., Schmidt, M. K., Setiawan, V. W., Shen, H., Siegel, E. M., Sieh, W., Singer, C. F., Slattery, M. L., Sorensen, K. D., Southey, M. C., Spurdle, A. B., Stanford, J. L., Stevens, V. L., Stintzing, S., Stone, J., Sundfeldt, K., Sutphen, R., Swerdlow, A. J., Tajara, E. H., Tangen, C. M., Tardon, A., Taylor, J. A., Teare, M. D., Teixeira, M. R., Terry, M. B., Terry, K. L., Thibodeau, S. N., Thomassen, M., Bjorge, L., Tischkowitz, M., Toland, A. E., Torres, D., Townsend, P. A., Travis, R. C., Tung, N., Tworoger, S. S., Ulrich, C. M., Usmani, N., Vachon, C. M., Van Nieuwenhuysen, E., Vega, A., Aguado-Barrera, M. E., Wang, Q., Webb, P. M., Weinberg, C. R., Weinstein, S., Weissler, M. C., Weitzel, J. N., West, C. M. L., White, E., Whittemore, A. S., Wichmann, H. -E., Wiklund, F., Winqvist, R., Wolk, A., Woll, P., Woods, M., Wu, A. H., Wu, X., Yannoukakos, D., Zheng, W., Zienolddiny, S., Ziogas, A., Zorn, K. K., Lane, J. M., Saxena, R., Thomas, D., Hung, R. J., Diergaarde, B., McKay, J., Peters, U., Hsu, L., Garcia-Closas, M., Eeles, R. A., Chenevix-Trench, G., Brennan, P. J., Haiman, C. A., Simard, J., Easton, D. F., Gruber, S. B., Pharoah, P. D. P., Price, A. L., Pasaniuc, B., Amos, C. I., Kraft, P., Lindstrom, S., Boccia S. (ORCID:0000-0002-1864-749X), Cadoni G. (ORCID:0000-0001-8244-784X), Chen C., Liu G., Wang Q., Jiang, X., Finucane, H. K., Schumacher, F. R., Schmit, S. L., Tyrer, J. P., Han, Y., Michailidou, K., Lesseur, C., Kuchenbaecker, K. B., Dennis, J., Conti, D. V., Casey, G., Gaudet, M. M., Huyghe, J. R., Albanes, D., Aldrich, M. C., Andrew, A. S., Andrulis, I. L., Anton-Culver, H., Antoniou, A. C., Antonenkova, N. N., Arnold, S. M., Aronson, K. J., Arun, B. K., Bandera, E. V., Barkardottir, R. B., Barnes, D. R., Batra, J., Beckmann, M. W., Benitez, J., Benlloch, S., Berchuck, A., Berndt, S. I., Bickeboller, H., Bien, S. A., Blomqvist, C., Boccia, S., Bogdanova, N. V., Bojesen, S. E., Bolla, M. K., Brauch, H., Brenner, H., Brenton, J. D., Brook, M. N., Brunet, J., Brunnstrom, H., Buchanan, D. D., Burwinkel, B., Butzow, R., Cadoni, G., Caldes, T., Caligo, M. A., Campbell, I., Campbell, P. T., Cancel-Tassin, G., Cannon-Albright, L., Campa, D., Caporaso, N., Carvalho, A. L., Chan, A. T., Chang-Claude, J., Chanock, S. J., Chen, Chen, Christiani, D. C., Claes, K. B. M., Claessens, F., Clements, J., Collee, J. M., Correa, M. C., Couch, F. J., Cox, A., Cunningham, J. M., Cybulski, C., Czene, K., Daly, M. B., deFazio, A., Devilee, P., Diez, O., Gago-Dominguez, M., Donovan, J. L., Dork, T., Duell, E. J., Dunning, A. M., Dwek, M., Eccles, D. M., Edlund, C. K., Edwards, D. R. V., Ellberg, C., Evans, D. G., Fasching, P. A., Ferris, R. L., Liloglou, T., Figueiredo, J. C., Fletcher, O., Fortner, R. T., Fostira, F., Franceschi, S., Friedman, E., Gallinger, S. J., Ganz, P. A., Garber, J., Garcia-Saenz, J. A., Gayther, S. A., Giles, G. G., Godwin, A. K., Goldberg, M. S., Goldgar, D. E., Goode, E. L., Goodman, M. T., Goodman, G., Grankvist, K., Greene, M. H., Gronberg, H., Gronwald, J., Guenel, P., Hakansson, N., Hall, P., Hamann, U., Hamdy, F. C., Hamilton, R. J., Hampe, J., Haugen, A., Heitz, F., Herrero, R., Hillemanns, P., Hoffmeister, M., Hogdall, E., Hong, Y. -C., Hopper, J. L., Houlston, R., Hulick, P. J., Hunter, D. J., Huntsman, D. G., Idos, G., Imyanitov, E. N., Ingles, S. A., Isaacs, C., Jakubowska, A., James, P., Jenkins, M. A., Johansson, M., John, E. M., Joshi, A. D., Kaneva, R., Karlan, B. Y., Kelemen, L. E., Kuhl, T., Khaw, K. -T., Khusnutdinova, E., Kibel, A. S., Kiemeney, L. A., Kim, J., Kjaer, S. K., Knight, J. A., Kogevinas, M., Kote-Jarai, Z., Koutros, S., Kristensen, V. N., Kupryjanczyk, J., Lacko, M., Lam, S., Lambrechts, D., Landi, M. T., Lazarus, P., Le, N. D., Lee, E., Lejbkowicz, F., Lenz, H. -J., Leslie, G., Lessel, D., Lester, J., Levine, D. A., Li, L., Li, C. I., Lindblom, A., Lindor, N. M., Liu, G., Loupakis, F., Lubinski, J., Maehle, L., Maier, C., Mannermaa, A., Marchand, L. L., Margolin, S., May, T., McGuffog, L., Meindl, A., Middha, P., Miller, A., Milne, R. L., MacInnis, R. J., Modugno, F., Montagna, M., Moreno, V., Moysich, K. B., Mucci, L., Muir, K., Mulligan, A. M., Nathanson, K. L., Neal, D. E., Ness, A. R., Neuhausen, S. L., Nevanlinna, H., Newcomb, P. A., Newcomb, L. F., Nielsen, F. C., Nikitina-Zake, L., Nordestgaard, B. G., Nussbaum, R. L., Offit, K., Olah, E., Olama, A. A. A., Olopade, O. I., Olshan, A. F., Olsson, H., Osorio, A., Pandha, H., Park, J. Y., Pashayan, N., Parsons, M. T., Pejovic, T., Penney, K. L., Peters, W. H. M., Phelan, C. M., Phipps, A. I., Plaseska-Karanfilska, D., Pring, M., Prokofyeva, D., Radice, P., Stefansson, K., Ramus, S. J., Raskin, L., Rennert, G., Rennert, H. S., van Rensburg, E. J., Riggan, M. J., Risch, H. A., Risch, A., Roobol, M. J., Rosenstein, B. S., Rossing, M. A., De Ruyck, K., Saloustros, E., Sandler, D. P., Sawyer, E. J., Schabath, M. B., Schleutker, J., Schmidt, M. K., Setiawan, V. W., Shen, H., Siegel, E. M., Sieh, W., Singer, C. F., Slattery, M. L., Sorensen, K. D., Southey, M. C., Spurdle, A. B., Stanford, J. L., Stevens, V. L., Stintzing, S., Stone, J., Sundfeldt, K., Sutphen, R., Swerdlow, A. J., Tajara, E. H., Tangen, C. M., Tardon, A., Taylor, J. A., Teare, M. D., Teixeira, M. R., Terry, M. B., Terry, K. L., Thibodeau, S. N., Thomassen, M., Bjorge, L., Tischkowitz, M., Toland, A. E., Torres, D., Townsend, P. A., Travis, R. C., Tung, N., Tworoger, S. S., Ulrich, C. M., Usmani, N., Vachon, C. M., Van Nieuwenhuysen, E., Vega, A., Aguado-Barrera, M. E., Wang, Q., Webb, P. M., Weinberg, C. R., Weinstein, S., Weissler, M. C., Weitzel, J. N., West, C. M. L., White, E., Whittemore, A. S., Wichmann, H. -E., Wiklund, F., Winqvist, R., Wolk, A., Woll, P., Woods, M., Wu, A. H., Wu, X., Yannoukakos, D., Zheng, W., Zienolddiny, S., Ziogas, A., Zorn, K. K., Lane, J. M., Saxena, R., Thomas, D., Hung, R. J., Diergaarde, B., McKay, J., Peters, U., Hsu, L., Garcia-Closas, M., Eeles, R. A., Chenevix-Trench, G., Brennan, P. J., Haiman, C. A., Simard, J., Easton, D. F., Gruber, S. B., Pharoah, P. D. P., Price, A. L., Pasaniuc, B., Amos, C. I., Kraft, P., Lindstrom, S., Boccia S. (ORCID:0000-0002-1864-749X), Cadoni G. (ORCID:0000-0001-8244-784X), Chen C., Liu G., and Wang Q.
Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Published: 2019

43. Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification

Author: Parsons, M. T., Tudini, E., Li, H., Hahnen, E., Wappenschmidt, B., Feliubadalo, L., Aalfs, C. M., Agata, S., Aittomaki, K., Alducci, E., Alonso-Cerezo, M. C., Arnold, N., Auber, B., Austin, R., Azzollini, J., Balmana, J., Barbieri, E., Bartram, C. R., Blanco, A., Blumcke, B., Bonache, S., Bonanni, B., Borg, A., Bortesi, B., Brunet, J., Bruzzone, C., Bucksch, K., Cagnoli, G., Caldes, T., Caliebe, A., Caligo, M. A., Calvello, M., Capone, G. L., Caputo, S. M., Carnevali, I., Carrasco, E., Caux-Moncoutier, V., Cavalli, P., Cini, G., Clarke, E. M., Concolino, Paola, Cops, E. J., Cortesi, L., Couch, F. J., Darder, E., de la Hoya, M., Dean, M., Debatin, I., Del Valle, J., Delnatte, C., Derive, N., Diez, O., Ditsch, N., Domchek, S. M., Dutrannoy, V., Eccles, D. M., Ehrencrona, H., Enders, U., Evans, D. G., Farra, C., Faust, U., Felbor, U., Feroce, I., Fine, M., Foulkes, W. D., Galvao, H. C. R., Gambino, G., Gehrig, A., Gensini, F., Gerdes, A. -M., Germani, A., Giesecke, J., Gismondi, V., Gomez, C., Gomez Garcia, E. B., Gonzalez, S., Grau, E., Grill, S., Gross, E., Guerrieri-Gonzaga, A., Guillaud-Bataille, M., Gutierrez-Enriquez, S., Haaf, T., Hackmann, K., Hansen, T. V. O., Harris, M., Hauke, J., Heinrich, T., Hellebrand, H., Herold, K. N., Honisch, E., Horvath, J., Houdayer, C., Hubbel, V., Iglesias, S., Izquierdo, A., James, P. A., Janssen, L. A. M., Jeschke, U., Kaulfuss, S., Keupp, K., Kiechle, M., Kolbl, A., Krieger, S., Kruse, T. A., Kvist, A., Lalloo, F., Larsen, M., Lattimore, V. L., Lautrup, C., Ledig, S., Leinert, E., Lewis, A. L., Lim, J., Loeffler, M., Lopez-Fernandez, A., Lucci Cordisco, Emanuela, Maass, N., Manoukian, S., Marabelli, M., Matricardi, L., Meindl, A., Michelli, R. D., Moghadasi, S., Moles-Fernandez, A., Montagna, M., Montalban, G., Monteiro, A. N., Montes, E., Mori, L., Moserle, L., Muller, C. R., Mundhenke, C., Naldi, N., Nathanson, K. L., Navarro, M., Nevanlinna, H., Nichols, C. B., Niederacher, D., Nielsen, H. R., Ong, K. -R., Pachter, N., Palmero, E. I., Papi, L., Pedersen, I. S., Peissel, B., Perez-Segura, P., Pfeifer, K., Pineda, M., Pohl-Rescigno, E., Poplawski, N. K., Porfirio, B., Quante, A. S., Ramser, J., Reis, R. M., Revillion, F., Rhiem, K., Riboli, B., Ritter, J., Rivera, D., Rofes, P., Rump, A., Salinas, M., Sanchez de Abajo, A. M., Schmidt, G., Schoenwiese, U., Seggewiss, J., Solanes, A., Steinemann, D., Stiller, M., Stoppa-Lyonnet, D., Sullivan, K. J., Susman, R., Sutter, C., Tavtigian, S. V., Teo, S. H., Teule, A., Thomassen, M., Tibiletti, M. G., Tischkowitz, M., Tognazzo, S., Toland, A. E., Tornero, E., Torngren, T., Torres-Esquius, S., Toss, A., Trainer, A. H., Tucker, K. M., van Asperen, C. J., van Mackelenbergh, M. T., Varesco, L., Vargas-Parra, G., Varon, R., Vega, A., Velasco, A., Vesper, A. -S., Viel, A., Vreeswijk, M. P. G., Wagner, S. A., Waha, A., Walker, L. C., Walters, R. J., Wang-Gohrke, S., Weber, B. H. F., Weichert, W., Wieland, K., Wiesmuller, L., Witzel, I., Wockel, A., Woodward, E. R., Zachariae, S., Zampiga, V., Zeder-Goss, C., Investigators, K., Lazaro, C., De Nicolo, A., Radice, P., Engel, C., Schmutzler, R. K., Goldgar, D. E., Spurdle, A. B., Concolino P., Lucci Cordisco E. (ORCID:0000-0002-6279-7604), Parsons, M. T., Tudini, E., Li, H., Hahnen, E., Wappenschmidt, B., Feliubadalo, L., Aalfs, C. M., Agata, S., Aittomaki, K., Alducci, E., Alonso-Cerezo, M. C., Arnold, N., Auber, B., Austin, R., Azzollini, J., Balmana, J., Barbieri, E., Bartram, C. R., Blanco, A., Blumcke, B., Bonache, S., Bonanni, B., Borg, A., Bortesi, B., Brunet, J., Bruzzone, C., Bucksch, K., Cagnoli, G., Caldes, T., Caliebe, A., Caligo, M. A., Calvello, M., Capone, G. L., Caputo, S. M., Carnevali, I., Carrasco, E., Caux-Moncoutier, V., Cavalli, P., Cini, G., Clarke, E. M., Concolino, Paola, Cops, E. J., Cortesi, L., Couch, F. J., Darder, E., de la Hoya, M., Dean, M., Debatin, I., Del Valle, J., Delnatte, C., Derive, N., Diez, O., Ditsch, N., Domchek, S. M., Dutrannoy, V., Eccles, D. M., Ehrencrona, H., Enders, U., Evans, D. G., Farra, C., Faust, U., Felbor, U., Feroce, I., Fine, M., Foulkes, W. D., Galvao, H. C. R., Gambino, G., Gehrig, A., Gensini, F., Gerdes, A. -M., Germani, A., Giesecke, J., Gismondi, V., Gomez, C., Gomez Garcia, E. B., Gonzalez, S., Grau, E., Grill, S., Gross, E., Guerrieri-Gonzaga, A., Guillaud-Bataille, M., Gutierrez-Enriquez, S., Haaf, T., Hackmann, K., Hansen, T. V. O., Harris, M., Hauke, J., Heinrich, T., Hellebrand, H., Herold, K. N., Honisch, E., Horvath, J., Houdayer, C., Hubbel, V., Iglesias, S., Izquierdo, A., James, P. A., Janssen, L. A. M., Jeschke, U., Kaulfuss, S., Keupp, K., Kiechle, M., Kolbl, A., Krieger, S., Kruse, T. A., Kvist, A., Lalloo, F., Larsen, M., Lattimore, V. L., Lautrup, C., Ledig, S., Leinert, E., Lewis, A. L., Lim, J., Loeffler, M., Lopez-Fernandez, A., Lucci Cordisco, Emanuela, Maass, N., Manoukian, S., Marabelli, M., Matricardi, L., Meindl, A., Michelli, R. D., Moghadasi, S., Moles-Fernandez, A., Montagna, M., Montalban, G., Monteiro, A. N., Montes, E., Mori, L., Moserle, L., Muller, C. R., Mundhenke, C., Naldi, N., Nathanson, K. L., Navarro, M., Nevanlinna, H., Nichols, C. B., Niederacher, D., Nielsen, H. R., Ong, K. -R., Pachter, N., Palmero, E. I., Papi, L., Pedersen, I. S., Peissel, B., Perez-Segura, P., Pfeifer, K., Pineda, M., Pohl-Rescigno, E., Poplawski, N. K., Porfirio, B., Quante, A. S., Ramser, J., Reis, R. M., Revillion, F., Rhiem, K., Riboli, B., Ritter, J., Rivera, D., Rofes, P., Rump, A., Salinas, M., Sanchez de Abajo, A. M., Schmidt, G., Schoenwiese, U., Seggewiss, J., Solanes, A., Steinemann, D., Stiller, M., Stoppa-Lyonnet, D., Sullivan, K. J., Susman, R., Sutter, C., Tavtigian, S. V., Teo, S. H., Teule, A., Thomassen, M., Tibiletti, M. G., Tischkowitz, M., Tognazzo, S., Toland, A. E., Tornero, E., Torngren, T., Torres-Esquius, S., Toss, A., Trainer, A. H., Tucker, K. M., van Asperen, C. J., van Mackelenbergh, M. T., Varesco, L., Vargas-Parra, G., Varon, R., Vega, A., Velasco, A., Vesper, A. -S., Viel, A., Vreeswijk, M. P. G., Wagner, S. A., Waha, A., Walker, L. C., Walters, R. J., Wang-Gohrke, S., Weber, B. H. F., Weichert, W., Wieland, K., Wiesmuller, L., Witzel, I., Wockel, A., Woodward, E. R., Zachariae, S., Zampiga, V., Zeder-Goss, C., Investigators, K., Lazaro, C., De Nicolo, A., Radice, P., Engel, C., Schmutzler, R. K., Goldgar, D. E., Spurdle, A. B., Concolino P., and Lucci Cordisco E. (ORCID:0000-0002-6279-7604)
Abstract: The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1,395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; and 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared with information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known nonpathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification.
Published: 2019

44. Genetics of the FANCA gene in familial pancreatic cancer

Author: Rogers, C D, Couch, F J, Brune, K, Martin, S T, Philips, J, Murphy, K M, Petersen, G, Yeo, C J, Hruban, R H, and Goggins, M
Published: 2004

45. Identification of nine new susceptibility loci for endometrial cancer

Author: O'Mara, T, Glubb, D, Amant, F, Annibali, D, Ashton, K, Attia, J, Auer, P, Beckmann, M, Black, A, Humphreys, M, Brauch, H, Brenner, H, Brinton, L, Buchanan, D, Burwinkel, B, Chang-Claude, J, Chanock, S, Chen, C, Chen, M, Cheng, T, Clarke, C, Clendenning, M, Cook, L, Couch, F, Cox, A, Crous-Bou, M, Czene, K, Day, F, Dennis, J, Depreeuw, J, Doherty, JA, Dork, T, Dowdy, S, Dürst, M, Ekici, A, Fasching, P, Fridley, B, Friedenreich, C, Fritschi, L, Fung, J, Garcia-Closas, M, Gaudet, M, Giles, G, Goode, E, Gorman, M, Haiman, C, Hall, P, Hankinson, S, Healey, C, Hein, A, Hillemanns, P, Hodgson, S, Hoivik, E, Holliday, E, Hopper, J, Hunter, D, Jones, A, Krakstad, C, Kristensen, V, Lambrechts, D, Le Marchand, L, Liang, X, Lindblom, A, Lissowska, J, Long, J, Lu, L, Magliocco, A, Martin, L, McEvoy, M, Meindl, A, Michailidou, K, Milne, R, Mints, M, Montgomery, G, Nassir, R, Olsson, H, Orlow, I, Sacerdote, G, Sarto, G, Schumacher, F, Scott, R, Setiawan, VW, Shah, M, Sheng, M, Shu, X-O, Southey, M, Swerdlow, A, Tham, E, Trovik, J, Wolk, A, Xia, L, Xiang, YB, Yang, H, Yu, H, Zheng, W, Pharoah, P, Dunning, A, Kraft, P, De Vivo, I, Tomlinson, I, Easton, D, Spurdle, A, and Thompson, D
Abstract: Endometrial cancer is the most commonly diagnosed cancer of the female reproductive tract in developed countries. Through genome-wide association studies (GWAS), we have previously identified eight risk loci for endometrial cancer. Here, we present an expanded meta-analysis of 12,906 endometrial cancer cases and 108,979 controls (including new genotype data for 5624 cases) and identify nine novel genome-wide significant loci, including a locus on 12q24.12 previously identified by meta-GWAS of endometrial and colorectal cancer. At five loci, expression quantitative trait locus (eQTL) analyses identify candidate causal genes; risk alleles at two of these loci associate with decreased expression of genes, which encode negative regulators of oncogenic signal transduction proteins (SH2B3 (12q24.12) and NF1 (17q11.2)). In summary, this study has doubled the number of known endometrial cancer risk loci and revealed candidate causal genes for future study.
Published: 2018

46. Gene-panel testing of breast and ovarian cancer patients identifies a recurrent RAD51C duplication

Author: Pelttari, L. M., Shimelis, H., Toiminen, H., Kvist, A., Törngren, T., Borg, Å., Blomqvist, C., Bützow, R., Couch, F., Aittomäki, K., Nevanlinna, H., Department of Obstetrics and Gynecology, Clinicum, University of Helsinki, HUSLAB, Department of Oncology, Department of Pathology, Medicum, Kristiina Aittomäki / Principal Investigator, Department of Medical and Clinical Genetics, and HUS Comprehensive Cancer Center
Subjects: RISK, endocrine system diseases, RAD51C, 1184 Genetics, developmental biology, physiology, GERMLINE MUTATIONS, BRCA1, CHEK2-ASTERISK-1100DELC, FAMILIES, PARALOGS, breast cancer, ovarian cancer, 3123 Gynaecology and paediatrics, gene-panel, PATTERNS, CONFER SUSCEPTIBILITY, COMPLEXES, 3111 Biomedicine, skin and connective tissue diseases, POPULATION
Abstract: Gene-panel sequencing allows comprehensive analysis of multiple genes simultaneously and is now routinely used in clinical mutation testing of high-risk breast and ovarian cancer patients. However, only BRCA1 and BRCA2 are often analyzed also for large genomic changes. Here, we have analyzed 10 clinically relevant susceptibility genes in 95 breast or ovarian cancer patients with gene-panel sequencing including also copy number variants (CNV) analysis for genomic changes. We identified 12 different pathogenic BRCA1, BRCA2, TP53, PTEN, CHEK2, or RAD51C mutations in 18 of 95 patients (19%). BRCA1/2 mutations were observed in 8 patients (8.4%) and CHEK2 protein-truncating mutations in 7 patients (7.4%). In addition, we identified a novel duplication encompassing most of the RAD51C gene. We further genotyped the duplication in breast or ovarian cancer families (n=1149), in unselected breast (n=1729) and ovarian cancer cohorts (n=553), and in population controls (n=1273). Seven additional duplication carries were observed among cases but none among controls. The duplication associated with ovarian cancer risk (3/590 of all ovarian cancer patients, 0.5%, P=.032 compared with controls) and was found to represent a large fraction of all identified RAD51C mutations in the Finnish population. Our data emphasizes the importance of comprehensive mutation analysis including CNV detection in all the relevant genes.
Published: 2018

47. The association between smoking and cancer incidence in BRCA1 and BRCA2 mutation carriers

Author: Kwang-Pil, Ko, Kim, Shana J, Huzarski, Tomasz, Gronwald, Jacek, Lubinski, Jan, Lynch, Henry T, Armel, Susan, Park, Sue K, Karlan, Beth, Singer, Christian F, Neuhausen, Susan L, Narod, Steven A, Kotsopoulos, Joanne, Snyder, C, Meschino, W, Demsky, R, Ainsworth, P, Panabaker, K, Taylor, M, Couch, F, Manoukian, S, Rappaport, C, Pasini, B, Daly, Mb, Olopade, O, Steele, L, Saal, H, Fallen, T, Wood, M, Mckinnon, W, Lemire, E, Chudley, Ae, Serfas, K, Sweet, K, Bordeleau, L, Elser, C, Panchal, S, Zakalik, D, Vadaparampil, St, Ginsburg, O, Hurst, S, Cullinane, Ca, Reilly, Re, Blum, Jl, Ross, T, Mauer, C, Kwong, A, Cybulski, C, Mccuaig, J, Merajver, S, Friedman, E, Rayson, D, Euhus, D, Foulkes, Wd, Senter, L, Tung, N, Weitzel, Jn, Eisen, A, Metcalfe, K, Eng, C, Pal, T, Evans, G, Moller, P, Rosen, B, and Isaacs, C.
Subjects: Adult, Ovarian Neoplasms, Heterozygote, endocrine system diseases, Incidence, Genes, BRCA2, Smoking, Genes, BRCA1, Middle Aged, BRCA1, BRCA2, Article, breast cancer, ovarian cancer, smoking, Disease Susceptibility, Female, Follow-Up Studies, Humans, Neoplasms, Risk Factors, Mutation, Genes, skin and connective tissue diseases
Abstract: Tobacco smoke is an established carcinogen, but the association between tobacco smoking and cancer risk in BRCA mutation carriers is not clear. The aim of this study was to evaluate prospectively the association between tobacco smoking and cancer incidence in a cohort of BRCA1 and BRCA2 mutation carriers. The study population consisted of unaffected BRCA mutation carriers. Information on lifestyle including smoking histories, reproductive factors, and past medical histories was obtained through questionnaires. Incident cancers were updated biennially via follow-up questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using time-dependent Cox regression models. There were 700 incident cancers diagnosed over 26,711 person-years of follow-up. The most frequent cancers seen in BRCA mutation carriers were breast (n = 428; 61%) and ovarian (n = 109; 15%) cancer. Compared to nonsmokers, (ever) smoking was associated with a modest increased risk of all cancers combined (HR = 1.17; 95%CI 1.01-1.37). Women in the highest group of total pack-years (4.3-9.8) had an increased risk of developing any cancer (HR = 1.27; 95%CI 1.04-1.56), breast cancer (HR = 1.33, 95%CI 1.02-1.75), and ovarian cancer (HR = 1.68; 95%CI 1.06-2.67) compared to never smokers. The associations between tobacco smoking and cancer did not differ by BRCA mutation type or by age at diagnosis. This prospective study suggests that tobacco smoking is associated with a modest increase in the risks of breast and ovarian cancer among women with BRCA1 or BRCA2 mutation.
Published: 2018

48. Chromosomal mapping of the rat Slc4a family of anion exchanger genes, Ael, Ae2, and Ae3

Author: Simon, J. S., Deshmukh, G., Couch, F. J., Merajver, S. D., Weber, B. L., Van Vooren, P., Tissil, F., Szpirer, J., Szpirer, C., Alper, S. L., Jacob, H. J., and Brosius, F. C.
Published: 1996
Full Text: View/download PDF

49. Abstract P1-12-10: Regimen-specific rates of chemotherapy-related amenorrhea in breast cancer survivors

Author: Gast, KC, primary, Cathcart-Rake, EJ, additional, Norman, A, additional, Eshragi, L, additional, Obidegwu, N, additional, Yost, K, additional, Nichols, HB, additional, Rosenberg, S, additional, Su, HI, additional, Stewart, E, additional, Couch, F, additional, Vachon, C, additional, and Ruddy, KJ, additional
Published: 2019
Full Text: View/download PDF

50. A transcriptome-wide association study of 229,000 women identifies new candidate susceptibility genes for breast cancer

Author: Wu, L. (Lang), Shi, W. (Wei), Long, J. (Jirong), Guo, X. (Xingyi), Michailidou, K. (Kyriaki), Beesley, J. (Jonathan), Bolla, M. K. (Manjeet K.), Shu, X.-O. (Xiao-Ou), Lu, Y. (Yingchang), Cai, Q. (Qiuyin), Al-Ejeh, F. (Fares), Rozali, E. (Esdy), Wang, Q. (Qin), Dennis, J. (Joe), Li, B. (Bingshan), Zeng, C. (Chenjie), Feng, H. (Helian), Gusev, A. (Alexander), Barfield, R. T. (Richard T.), Andrulis, I. L. (Irene L.), Anton-Culver, H. (Hoda), Arndt, V. (Volker), Aronson, K. J. (Kristan J.), Auer, P. L. (Paul L.), Barrdahl, M. (Myrto), Baynes, C. (Caroline), Beckmann, M. W. (Matthias W.), Benitez, J. (Javier), Bermisheva, M. (Marina), Blomqvist, C. (Carl), Bogdanova, N. V. (Natalia V.), Bojesen, S. E. (Stig E.), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Brinton, L. (Louise), Broberg, P. (Per), Brucker, S. Y. (Sara Y.), Burwinkel, B. (Barbara), Caldes, T. (Trinidad), Canzian, F. (Federico), Carter, B. D. (Brian D.), Castelao, J. E. (J. Esteban), Chang-Claude, J. (Jenny), Chen, X. (Xiaoqing), Cheng, T. D. (Ting-Yuan David), Christiansen, H. (Hans), Clarke, C. L. (Christine L.), Collee, M. (Margriet), Cornelissen, S. (Sten), Couch, F. J. (Fergus J.), Cox, D. (David), Cox, A. (Angela), Cross, S. S. (Simon S.), Cunningham, J. M. (Julie M.), Czene, K. (Kamila), Daly, M. B. (Mary B.), Devilee, P. (Peter), Doheny, K. F. (Kimberly F.), Dork, T. (Thilo), dos-Santos-Silva, I. (Isabel), Dumont, M. (Martine), Dwek, M. (Miriam), Eccles, D. M. (Diana M.), Eilber, U. (Ursula), Eliassen, A. H. (A. Heather), Engel, C. (Christoph), Eriksson, M. (Mikael), Fachal, L. (Laura), Fasching, P. A. (Peter A.), Figueroa, J. (Jonine), Flesch-Janys, D. (Dieter), Fletcher, O. (Olivia), Flyger, H. (Henrik), Fritschi, L. (Lin), Gabrielson, M. (Marike), Gago-Dominguez, M. (Manuela), Gapstur, S. M. (Susan M.), Garcia-Closas, M. (Montserrat), Gaudet, M. M. (Mia M.), Ghoussaini, M. (Maya), Giles, G. G. (Graham G.), Goldberg, M. S. (Mark S.), Goldgar, D. E. (David E.), Gonzalez-Neira, A. (Anna), Guenel, P. (Pascal), Hahnen, E. (Eric), Haiman, C. A. (Christopher A.), Hakansson, N. (Niclas), Hall, P. (Per), Hallberg, E. (Emily), Hamann, U. (Ute), Harrington, P. (Patricia), Hein, A. (Alexander), Hicks, B. (Belynda), Hillemanns, P. (Peter), Hollestelle, A. (Antoinette), Hoover, R. N. (Robert N.), Hopper, J. L. (John L.), Huang, G. (Guanmengqian), Humphreys, K. (Keith), Hunter, D. J. (David J.), Jakubowska, A. (Anna), Janni, W. (Wolfgang), John, E. M. (Esther M.), Johnson, N. (Nichola), Jones, K. (Kristine), Jones, M. E. (Michael E.), Jung, A. (Audrey), Kaaks, R. (Rudolf), Kerin, M. J. (Michael J.), Khusnutdinova, E. (Elza), Kosma, V.-M. (Veli-Matti), Kristensen, V. N. (Vessela N.), Lambrechts, D. (Diether), Le Marchand, L. (Loic), Li, J. (Jingmei), Lindstrom, S. (Sara), Lissowska, J. (Jolanta), Lo, W.-Y. (Wing-Yee), Loibl, S. (Sibylle), Lubinski, J. (Jan), Luccarini, C. (Craig), Lux, M. P. (Michael P.), MacInnis, R. J. (Robert J.), Maishman, T. (Tom), Kostovska, I. M. (Ivana Maleva), Mannermaa, A. (Arto), Manson, J. E. (Joann E.), Margolin, S. (Sara), Mavroudis, D. (Dimitrios), Meijers-Heijboer, H. (Hanne), Meindl, A. (Alfons), Menon, U. (Usha), Meyer, J. (Jeffery), Mulligan, A. M. (Anna Marie), Neuhausen, S. L. (Susan L.), Nevanlinna, H. (Heli), Neven, P. (Patrick), Nielsen, S. F. (Sune F.), Nordestgaard, B. G. (Borge G.), Olopade, O. I. (Olufunmilayo I.), Olson, J. E. (Janet E.), Olsson, H. (Hakan), Peterlongo, P. (Paolo), Peto, J. (Julian), Plaseska-Karanfilska, D. (Dijana), Prentice, R. (Ross), Presneau, N. (Nadege), Pylkäs, K. (Katri), Rack, B. (Brigitte), Radice, P. (Paolo), Rahman, N. (Nazneen), Rennert, G. (Gad), Rennert, H. S. (Hedy S.), Rhenius, V. (Valerie), Romero, A. (Atocha), Romm, J. (Jane), Rudolph, A. (Anja), Saloustros, E. (Emmanouil), Sandler, D. P. (Dale P.), Sawyer, E. J. (Elinor J.), Schmidt, M. K. (Marjanka K.), Schmutzler, R. K. (Rita K.), Schneeweiss, A. (Andreas), Scott, R. J. (Rodney J.), Scott, C. G. (Christopher G.), Seal, S. (Sheila), Shah, M. (Mitul), Shrubsole, M. J. (Martha J.), Smeets, A. (Ann), Southey, M. C. (Melissa C.), Spinelli, J. J. (John J.), Stone, J. (Jennifer), Surowy, H. (Harald), Swerdlow, A. J. (Anthony J.), Tamimi, R. M. (Rulla M.), Tapper, W. (William), Taylor, J. A. (Jack A.), Terry, M. B. (Mary Beth), Tessier, D. C. (Daniel C.), Thomas, A. (Abigail), Thone, K. (Kathrin), Tollenaar, R. A. (Rob A. E. M.), Torres, D. (Diana), Truong, T. (Therese), Untch, M. (Michael), Vachon, C. (Celine), Van den Berg, D. (David), Vincent, D. (Daniel), Waisfisz, Q. (Quinten), Weinberg, C. R. (Clarice R.), Wendt, C. (Camilla), Whittemore, A. S. (Alice S.), Wildiers, H. (Hans), Willett, W. C. (Walter C.), Winqvist, R. (Robert), Wolk, A. (Alicja), Xia, L. (Lucy), Yang, X. R. (Xiaohong R.), Ziogas, A. (Argyrios), Ziv, E. (Elad), Dunning, A. M. (Alison M.), Pharoah, P. D. (Paul D. P.), Simard, J. (Jacques), Milne, R. L. (Roger L.), Edwards, S. L. (Stacey L.), Kraft, P. (Peter), Easton, D. F. (Douglas F.), Chenevix-Trench, G. (Georgia), Zheng, W. (Wei), Wu, L. (Lang), Shi, W. (Wei), Long, J. (Jirong), Guo, X. (Xingyi), Michailidou, K. (Kyriaki), Beesley, J. (Jonathan), Bolla, M. K. (Manjeet K.), Shu, X.-O. (Xiao-Ou), Lu, Y. (Yingchang), Cai, Q. (Qiuyin), Al-Ejeh, F. (Fares), Rozali, E. (Esdy), Wang, Q. (Qin), Dennis, J. (Joe), Li, B. (Bingshan), Zeng, C. (Chenjie), Feng, H. (Helian), Gusev, A. (Alexander), Barfield, R. T. (Richard T.), Andrulis, I. L. (Irene L.), Anton-Culver, H. (Hoda), Arndt, V. (Volker), Aronson, K. J. (Kristan J.), Auer, P. L. (Paul L.), Barrdahl, M. (Myrto), Baynes, C. (Caroline), Beckmann, M. W. (Matthias W.), Benitez, J. (Javier), Bermisheva, M. (Marina), Blomqvist, C. (Carl), Bogdanova, N. V. (Natalia V.), Bojesen, S. E. (Stig E.), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Brinton, L. (Louise), Broberg, P. (Per), Brucker, S. Y. (Sara Y.), Burwinkel, B. (Barbara), Caldes, T. (Trinidad), Canzian, F. (Federico), Carter, B. D. (Brian D.), Castelao, J. E. (J. Esteban), Chang-Claude, J. (Jenny), Chen, X. (Xiaoqing), Cheng, T. D. (Ting-Yuan David), Christiansen, H. (Hans), Clarke, C. L. (Christine L.), Collee, M. (Margriet), Cornelissen, S. (Sten), Couch, F. J. (Fergus J.), Cox, D. (David), Cox, A. (Angela), Cross, S. S. (Simon S.), Cunningham, J. M. (Julie M.), Czene, K. (Kamila), Daly, M. B. (Mary B.), Devilee, P. (Peter), Doheny, K. F. (Kimberly F.), Dork, T. (Thilo), dos-Santos-Silva, I. (Isabel), Dumont, M. (Martine), Dwek, M. (Miriam), Eccles, D. M. (Diana M.), Eilber, U. (Ursula), Eliassen, A. H. (A. Heather), Engel, C. (Christoph), Eriksson, M. (Mikael), Fachal, L. (Laura), Fasching, P. A. (Peter A.), Figueroa, J. (Jonine), Flesch-Janys, D. (Dieter), Fletcher, O. (Olivia), Flyger, H. (Henrik), Fritschi, L. (Lin), Gabrielson, M. (Marike), Gago-Dominguez, M. (Manuela), Gapstur, S. M. (Susan M.), Garcia-Closas, M. (Montserrat), Gaudet, M. M. (Mia M.), Ghoussaini, M. (Maya), Giles, G. G. (Graham G.), Goldberg, M. S. (Mark S.), Goldgar, D. E. (David E.), Gonzalez-Neira, A. (Anna), Guenel, P. (Pascal), Hahnen, E. (Eric), Haiman, C. A. (Christopher A.), Hakansson, N. (Niclas), Hall, P. (Per), Hallberg, E. (Emily), Hamann, U. (Ute), Harrington, P. (Patricia), Hein, A. (Alexander), Hicks, B. (Belynda), Hillemanns, P. (Peter), Hollestelle, A. (Antoinette), Hoover, R. N. (Robert N.), Hopper, J. L. (John L.), Huang, G. (Guanmengqian), Humphreys, K. (Keith), Hunter, D. J. (David J.), Jakubowska, A. (Anna), Janni, W. (Wolfgang), John, E. M. (Esther M.), Johnson, N. (Nichola), Jones, K. (Kristine), Jones, M. E. (Michael E.), Jung, A. (Audrey), Kaaks, R. (Rudolf), Kerin, M. J. (Michael J.), Khusnutdinova, E. (Elza), Kosma, V.-M. (Veli-Matti), Kristensen, V. N. (Vessela N.), Lambrechts, D. (Diether), Le Marchand, L. (Loic), Li, J. (Jingmei), Lindstrom, S. (Sara), Lissowska, J. (Jolanta), Lo, W.-Y. (Wing-Yee), Loibl, S. (Sibylle), Lubinski, J. (Jan), Luccarini, C. (Craig), Lux, M. P. (Michael P.), MacInnis, R. J. (Robert J.), Maishman, T. (Tom), Kostovska, I. M. (Ivana Maleva), Mannermaa, A. (Arto), Manson, J. E. (Joann E.), Margolin, S. (Sara), Mavroudis, D. (Dimitrios), Meijers-Heijboer, H. (Hanne), Meindl, A. (Alfons), Menon, U. (Usha), Meyer, J. (Jeffery), Mulligan, A. M. (Anna Marie), Neuhausen, S. L. (Susan L.), Nevanlinna, H. (Heli), Neven, P. (Patrick), Nielsen, S. F. (Sune F.), Nordestgaard, B. G. (Borge G.), Olopade, O. I. (Olufunmilayo I.), Olson, J. E. (Janet E.), Olsson, H. (Hakan), Peterlongo, P. (Paolo), Peto, J. (Julian), Plaseska-Karanfilska, D. (Dijana), Prentice, R. (Ross), Presneau, N. (Nadege), Pylkäs, K. (Katri), Rack, B. (Brigitte), Radice, P. (Paolo), Rahman, N. (Nazneen), Rennert, G. (Gad), Rennert, H. S. (Hedy S.), Rhenius, V. (Valerie), Romero, A. (Atocha), Romm, J. (Jane), Rudolph, A. (Anja), Saloustros, E. (Emmanouil), Sandler, D. P. (Dale P.), Sawyer, E. J. (Elinor J.), Schmidt, M. K. (Marjanka K.), Schmutzler, R. K. (Rita K.), Schneeweiss, A. (Andreas), Scott, R. J. (Rodney J.), Scott, C. G. (Christopher G.), Seal, S. (Sheila), Shah, M. (Mitul), Shrubsole, M. J. (Martha J.), Smeets, A. (Ann), Southey, M. C. (Melissa C.), Spinelli, J. J. (John J.), Stone, J. (Jennifer), Surowy, H. (Harald), Swerdlow, A. J. (Anthony J.), Tamimi, R. M. (Rulla M.), Tapper, W. (William), Taylor, J. A. (Jack A.), Terry, M. B. (Mary Beth), Tessier, D. C. (Daniel C.), Thomas, A. (Abigail), Thone, K. (Kathrin), Tollenaar, R. A. (Rob A. E. M.), Torres, D. (Diana), Truong, T. (Therese), Untch, M. (Michael), Vachon, C. (Celine), Van den Berg, D. (David), Vincent, D. (Daniel), Waisfisz, Q. (Quinten), Weinberg, C. R. (Clarice R.), Wendt, C. (Camilla), Whittemore, A. S. (Alice S.), Wildiers, H. (Hans), Willett, W. C. (Walter C.), Winqvist, R. (Robert), Wolk, A. (Alicja), Xia, L. (Lucy), Yang, X. R. (Xiaohong R.), Ziogas, A. (Argyrios), Ziv, E. (Elad), Dunning, A. M. (Alison M.), Pharoah, P. D. (Paul D. P.), Simard, J. (Jacques), Milne, R. L. (Roger L.), Edwards, S. L. (Stacey L.), Kraft, P. (Peter), Easton, D. F. (Douglas F.), Chenevix-Trench, G. (Georgia), and Zheng, W. (Wei)
Abstract: The breast cancer risk variants identified in genome-wide association studies explain only a small fraction of the familial relative risk, and the genes responsible for these associations remain largely unknown. To identify novel risk loci and likely causal genes, we performed a transcriptome-wide association study evaluating associations of genetically predicted gene expression with breast cancer risk in 122,977 cases and 105,974 controls of European ancestry. We used data from the Genotype-Tissue Expression Project to establish genetic models to predict gene expression in breast tissue and evaluated model performance using data from The Cancer Genome Atlas. Of the 8,597 genes evaluated, significant associations were identified for 48 at a Bonferroni-corrected threshold of P < 5.82 × 10−6, including 14 genes at loci not yet reported for breast cancer. We silenced 13 genes and showed an effect for 11 on cell proliferation and/or colony-forming efficiency. Our study provides new insights into breast cancer genetics and biology.
Published: 2018

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Region

Database

Publisher

368 results on '"Couch, F."'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources