© 1999 by Oxford University Press
Journal of the National Cancer Institute, Vol. 91, No. 15, 1310-1316,
August 4, 1999
© 1999 Oxford University Press
REPORTS |
Cancer Risks in BRCA2 Mutation Carriers
Affiliation of authors: Cancer Research Campaign (CRC) Genetic Epidemiology Unit, Strangeways Research Laboratory, Cambridge, U.K. See "Appendix" section for a list of the consortium members.
Correspondence to: Douglas Easton, Ph.D., CRC Genetic Epidemiology Unit, Strangeways Research Laboratory, Worts Causeway, Cambridge, U.K. (e-mail: douglas{at}srl.cam.ac.uk).
BACKGROUND: Carriers of germline mutations in the BRCA2 gene are known to be at high risk of breast and ovarian cancers, but the risks of other cancers in mutation carriers are uncertain. We investigated these risks in 173 breast-ovarian cancer families with BRCA2 mutations identified at 20 centers in Europe and North America. METHODS: Other cancer occurrence was determined in a final cohort of 3728 individuals, among whom 681 persons had breast or ovarian cancer and 3047 persons either were known mutation carriers, were first-degree relatives of known mutation carriers, or were first-degree relatives of breast or ovarian cancer patients. Incidence rates were compared with population-specific incidence rates, and relative risks (RRs) to carriers, together with 95% confidence intervals (CIs), were estimated by use of a maximum likelihood approach. Three hundred thirty-three other cancers occurred in this cohort. RESULTS: Statistically significant increases in risks were observed for prostate cancer (estimated RR = 4.65; 95% CI = 3.48-6.22), pancreatic cancer (RR = 3.51; 95% CI = 1.87-6.58), gallbladder and bile duct cancer (RR = 4.97; 95% CI = 1.50-16.52), stomach cancer (RR = 2.59; 95%CI = 1.46-4.61), and malignant melanoma (RR = 2.58; 95% CI = 1.28-5.17). The RR for prostate cancer for men below the age of 65 years was 7.33 (95% CI = 4.66-11.52). Among women who had already developed breast cancer, the cumulative risks of a second, contralateral breast cancer and of ovarian cancer by the age of 70 years were estimated to be 52.3% (95% CI = 41.7%-61.0%) and 15.9% (95% CI = 8.8%-22.5%), respectively. CONCLUSIONS: In addition to the large risks of breast and ovarian cancers, BRCA2 mutations may be associated with increased risks of several other cancers.
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T. R. Rebbeck, T. Friebel, H. T. Lynch, S. L. Neuhausen, L. van 't Veer, J. E. Garber, G. R. Evans, S. A. Narod, C. Isaacs, E. Matloff, et al. Bilateral Prophylactic Mastectomy Reduces Breast Cancer Risk in BRCA1 and BRCA2 Mutation Carriers: The PROSE Study Group J. Clin. Oncol., March 15, 2004; 22(6): 1055 - 1062. [Abstract] [Full Text] [PDF]
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A. Liede, B. Y. Karlan, and S. A. Narod Cancer Risks for Male Carriers of Germline Mutations in BRCA1 or BRCA2: A Review of the Literature J. Clin. Oncol., February 15, 2004; 22(4): 735 - 742. [Abstract] [Full Text] [PDF]
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C. Cybulski, B. Gorski, T. Debniak, B. Gliniewicz, M. Mierzejewski, B. Masojc, A. Jakubowska, J. Matyjasik, E. Zlowocka, A. Sikorski, et al. NBS1 Is a Prostate Cancer Susceptibility Gene Cancer Res., February 15, 2004; 64(4): 1215 - 1219. [Abstract] [Full Text] [PDF]
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B. L. Niell, G. Rennert, J. D. Bonner, R. Almog, L. P. Tomsho, and S. B. Gruber BRCA1 and BRCA2 Founder Mutations and the Risk of Colorectal Cancer J Natl Cancer Inst, January 7, 2004; 96(1): 15 - 21. [Abstract] [Full Text] [PDF]
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T. Kirchhoff, J. M. Satagopan, N. D. Kauff, H. Huang, P. Kolachana, C. Palmer, H. Rapaport, K. Nafa, N. A. Ellis, and K. Offit Frequency of BRCA1 and BRCA2 Mutations in Unselected Ashkenazi Jewish Patients With Colorectal Cancer J Natl Cancer Inst, January 7, 2004; 96(1): 68 - 70. [Abstract] [Full Text] [PDF]
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K. E. Nichols, J. A. Heath, D. Friedman, J. A. Biegel, A. Ganguly, P. Mauch, and L. Diller TP53, BRCA1, and BRCA2 Tumor Suppressor Genes Are Not Commonly Mutated in Survivors of Hodgkin's Disease With Second Primary Neoplasms J. Clin. Oncol., December 15, 2003; 21(24): 4505 - 4509. [Abstract] [Full Text] [PDF]
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B. N. Peshkin, C. Isaacs, C. Finch, S. Kent, and M. D. Schwartz Tamoxifen As Chemoprevention in BRCA1 and BRCA2 Mutation Carriers With Breast Cancer: A Pilot Survey of Physicians J. Clin. Oncol., December 1, 2003; 21(23): 4322 - 4328. [Abstract] [Full Text] [PDF]
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D. A. Levine, P. A. Argenta, C. J. Yee, D. S. Marshall, N. Olvera, F. Bogomolniy, J. A. Rahaman, M. E. Robson, K. Offit, R. R. Barakat, et al. Fallopian Tube and Primary Peritoneal Carcinomas Associated With BRCA Mutations J. Clin. Oncol., November 15, 2003; 21(22): 4222 - 4227. [Abstract] [Full Text] [PDF]
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A. Shimamura and A. D. D'Andrea Subtyping of Fanconi anemia patients: implications for clinical management Blood, November 1, 2003; 102(9): 3459 - 3459. [Full Text] [PDF]
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K. Offit, O. Levran, B. Mullaney, K. Mah, K. Nafa, S. D. Batish, R. Diotti, H. Schneider, A. Deffenbaugh, T. Scholl, et al. Shared Genetic Susceptibility to Breast Cancer, Brain Tumors, and Fanconi Anemia J Natl Cancer Inst, October 15, 2003; 95(20): 1548 - 1551. [Abstract] [Full Text] [PDF]
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B. A. Mincey Genetics and the Management of Women at High Risk for Breast Cancer Oncologist, October 1, 2003; 8(5): 466 - 473. [Abstract] [Full Text] [PDF]
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T Ikonen, M P Matikainen, K Syrjakoski, N Mononen, P A Koivisto, A Rokman, E H Seppala, O-P Kallioniemi, T L J Tammela, and J Schleutker BRCA1 and BRCA2 mutations have no major role in predisposition to prostate cancer in Finland J. Med. Genet., August 1, 2003; 40(8): e98 - 98. [Full Text] [PDF]
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 E. A. Hurst, J. W. Harbour, and L. A. Cornelius Ocular Melanoma: A Review and the Relationship to Cutaneous Melanoma Arch Dermatol, August 1, 2003; 139(8): 1067 - 1073. [Abstract] [Full Text] [PDF]
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H. M. Klaren, L. J. van't Veer, F. E. van Leeuwen, and M. A. Rookus Potential for Bias in Studies on Efficacy of Prophylactic Surgery for BRCA1 and BRCA2 Mutation J Natl Cancer Inst, July 2, 2003; 95(13): 941 - 947. [Full Text] [PDF]
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A. Evangelou, M. Letarte, I. Jurisica, M. Sultan, K. J. Murphy, B. Rosen, and T. J. Brown Loss of Coordinated Androgen Regulation in Nonmalignant Ovarian Epithelial Cells with BRCA1/2 Mutations and Ovarian Cancer Cells Cancer Res., May 15, 2003; 63(10): 2416 - 2424. [Abstract] [Full Text] [PDF]
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H. Meijers-Heijboer, C. T.M. Brekelmans, M. Menke-Pluymers, C. Seynaeve, A. Baalbergen, C. Burger, E. Crepin, A. W.M. van den Ouweland, B. van Geel, and J. G.M. Klijn Use of Genetic Testing and Prophylactic Mastectomy and Oophorectomy in Women With Breast or Ovarian Cancer From Families With a BRCA1 or BRCA2 Mutation J. Clin. Oncol., May 1, 2003; 21(9): 1675 - 1681. [Abstract] [Full Text] [PDF]
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P. A. Daly, C. Nolan, A. Green, W. Ormiston, N. Cody, T. McDevitt, B. O'hIci, D. Byrne, E. McDermott, D. N. Carney, et al. Predictive testing for BRCA1 and 2 mutations: a male contribution Ann. Onc., April 1, 2003; 14(4): 549 - 553. [Abstract] [Full Text] [PDF]
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S. M. Domchek, A. Eisen, K. Calzone, J. Stopfer, A. Blackwood, and B. L. Weber Application of Breast Cancer Risk Prediction Models in Clinical Practice J. Clin. Oncol., February 15, 2003; 21(4): 593 - 601. [Abstract] [Full Text] [PDF]
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D. I. Kutler, B. Singh, J. Satagopan, S. D. Batish, M. Berwick, P. F. Giampietro, H. Hanenberg, and A. D. Auerbach A 20-year perspective on the International Fanconi Anemia Registry (IFAR) Blood, February 15, 2003; 101(4): 1249 - 1256. [Abstract] [Full Text] [PDF]
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K. Hemminki and C. Granstrom Re: Risk of Subsequent Cancer Following Breast Cancer in Men J Natl Cancer Inst, December 18, 2002; 94(24): 1892 - 1892. [Full Text] [PDF]
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G. Palmieri, G. Palomba, A. Cossu, M. Pisano, M. F. Dedola, M. G. Sarobba, A. Farris, N. Olmeo, A. Contu, A. Pasca, et al. BRCA1 and BRCA2 germline mutations in Sardinian breast cancer families and their implications for genetic counseling Ann. Onc., December 1, 2002; 13(12): 1899 - 1907. [Abstract] [Full Text] [PDF]
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J. M. Satagopan, J. Boyd, N. D. Kauff, M. Robson, L. Scheuer, S. Narod, and K. Offit Ovarian Cancer Risk in Ashkenazi Jewish Carriers of BRCA1 and BRCA2 Mutations Clin. Cancer Res., December 1, 2002; 8(12): 3776 - 3781. [Abstract] [Full Text] [PDF]
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D. Thompson, D. F. Easton, and the Breast Cancer Linkage Consortium Cancer Incidence in BRCA1 Mutation Carriers J Natl Cancer Inst, September 18, 2002; 94(18): 1358 - 1365. [Abstract] [Full Text] [PDF]
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