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Breast and Ovarian Cancer Risks Due to Inherited Mutations in BRCA1 and BRCA2
Mary-Claire King,1*Joan H. Marks,2Jessica B. Mandell2* The New York Breast Cancer Study Group3
Risks of breast and ovarian cancer were determined for AshkenaziJewish women with inherited mutations in the tumor suppressorgenes BRCA1 and BRCA2. We selected 1008 index cases, regardlessof family history of cancer, and carried out molecular analysisacross entire families. The lifetime risk of breast cancer amongfemale mutation carriers was 82%, similar to risks in familieswith many cases. Risks appear to be increasing with time: Breastcancer risk by age 50 among mutation carriers born before 1940was 24%, but among those born after 1940 it was 67%. Lifetimerisks of ovarian cancer were 54% for BRCA1 and 23% for BRCA2mutation carriers. Physical exercise and lack of obesity inadolescence were associated with significantly delayed breastcancer onset.
1 Departments of Medicine and Genome Sciences, University of Washington, Seattle, WA 98195, USA. 2 Sarah Lawrence College Graduate Program in Human Genetics, Bronxville, NY 10708, USA. 3 The New York Breast Cancer Study Group includes Albert Einstein College of Medicine/Montefiore Medical Center (Myrna Ben-Yishay, Janice P. Dutcher, Susan J. Gross, Carolyn D. Runowicz, Usha Venkatraj); Beth Israel Medical Center (Katherine Daley, Gayna Havens, Victor B. Penchaszadeh, Bert Petersen, Peter Pressman, Diana Punales-Morejon); Columbia Presbyterian Medical Center, Columbia University (Karen H. Antman, Donna Russo); Englewood Hospital and Medical Center (Sherry L. Campbell Grumet); Greenwich Hospital, Yale Cancer Center (Ellen T. Matloff, Arthur Rosenberg); Hackensack University Medical Center (Sivya Twersky, Susan E. White, Debra Capko); Memorial Sloan-Kettering Cancer Center (Robin Camhi Baum, Patrick Borgen, Karen L. Brown, Emily Glogowski, Bruce R. Haas, Heather Hampel, Deborah A. McDermott, Larry Norton, Heather Hanson Pierce, Mark Pinto, Mark Robson, Lauren Scheuer, Charlene J. Schulz, Kenneth Offit); New York University Medical Center (Ruth Oratz, Harry Ostrer, Elsa Reich); North Shore University Hospital (Martin Bialer, Lois Greenberg, Yelena Kemel, Jill Lundberg, Carrie A. McKenna, Lakshmi Mehta, Sujatha Sastry); Private Practitioners (Ernest J. Greenberg, Paul A. C. Greenberg, Thomas Kolb, Jacob Lichy); Sarah Lawrence College (Jessica Benjoya Mandell, Janice L. Berliner, Joan H. Marks); Stamford Hospital, Bennett Cancer Center (Jennifer Scalia Wilbur, Isadore Tepler, Paul L. Weinstein); Strang Cancer Prevention Center (Mary-Kay Dabney, Gladys Rosenthal, Fred Gilbert, Susan Oliveria, Michael Osborne); University of Washington (Katie Hale Coats, Judy Hull, Mary-Claire King, Ming K. Lee, Jan E. Morrow, Kelly N. Owens, Stacey Shiovitz, Sunday Stray, Tom Walsh, Vanessa L. Walsh); White Plains Hospital Center (Robert D. Burk, Rochelle Demsky, Kathleen Duffy, Mark A. Fialk, Amy R. Mank-Seymour, Heather L. Shappell).
* To whom correspondence should be addressed. E-mail: mcking{at}u.washington.edu (M.C.K); jmandell{at}mail.slc.edu (J.B.M.)
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LETTERS
Douglas F. Easton, John L. Hopper, Duncan C. Thomas, Antonis Antoniou, Paul D. P. Pharoah, Alice S. Whittemore, Robert W. Haile;, Sholom Wacholder, Jeffery P. Struewing, Patricia Hartge, Mark H. Greene, Margaret A. Tucker;, and Mary-Claire King (24 December 2004) Science306 (5705), 2187c.
[DOI: 10.1126/science.306.5705.2187c] |Full Text »|PDF »|Supporting Online Material »
PERSPECTIVES
Ephrat Levy-Lahad and Sharon E. Plon (24 October 2003) Science302 (5645), 574.
[DOI: 10.1126/science.1091465] |Summary »|Full Text »|PDF »
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[DOI: 10.1126/science.302.5645.592] |Summary »|Full Text »|PDF »
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Lifetime Risk of Melanoma in CDKN2A Mutation Carriers in a Population-Based Sample.
C. B. Begg, I. Orlow, A. J. Hummer, B. K. Armstrong, A. Kricker, L. D. Marrett, R. C. Millikan, S. B. Gruber, H. Anton-Culver, R. Zanetti, et al. (2005)
J Natl Cancer Inst
97, 1507-1515
|Abstract »|Full Text »|PDF »
Quality-of-Life Effects of Prophylactic Salpingo-Oophorectomy Versus Gynecologic Screening Among Women at Increased Risk of Hereditary Ovarian Cancer.
J. B. Madalinska, J. Hollenstein, E. Bleiker, M. van Beurden, H. B. Valdimarsdottir, L. F. Massuger, K. N. Gaarenstroom, M. J.E. Mourits, R. H.M. Verheijen, E. B.L. van Dorst, et al. (2005)
J. Clin. Oncol.
23, 6890-6898
|Abstract »|Full Text »|PDF »
Genetic Risk Assessment and BRCA Mutation Testing for Breast and Ovarian Cancer Susceptibility: Recommendation Statement.
Genetic Risk Assessment and BRCA Mutation Testing for Breast and Ovarian Cancer Susceptibility: Systematic Evidence Review for the U.S. Preventive Services Task Force.
H. D. Nelson, L. H. Huffman, R. Fu, and E. L. Harris (2005)
Ann Intern Med
143, 362-379
|Abstract »|Full Text »|PDF »
Cancer risks in BRCA2 families: estimates for sites other than breast and ovary.
C J van Asperen, R M Brohet, E J Meijers-Heijboer, N Hoogerbrugge, S Verhoef, H F A Vasen, M G E M Ausems, F H Menko, E B Gomez Garcia, J G M Klijn, et al. (2005)
J. Med. Genet.
42, 711-719
|Abstract »|Full Text »|PDF »
A Haplotype-Based Case-Control Study of BRCA1 and Sporadic Breast Cancer Risk.
M. L. Freedman, K. L. Penney, D. O. Stram, S. Riley, R. McKean-Cowdin, L. Le Marchand, D. Altshuler, and C. A. Haiman (2005)
Cancer Res.
65, 7516-7522
|Abstract »|Full Text »|PDF »
Breast and ovarian cancer risks to carriers of the BRCA1 5382insC and 185delAG and BRCA2 6174delT mutations: a combined analysis of 22 population based studies.
A C Antoniou, P D P Pharoah, S Narod, H A Risch, J E Eyfjord, J L Hopper, H Olsson, O Johannsson, A Borg, B Pasini, et al. (2005)
J. Med. Genet.
42, 602-603
|Abstract »|Full Text »|PDF »
Interaction between genetic susceptibility and early-life environmental exposure determines tumor-suppressor-gene penetrance.
J. D. Cook, B. J. Davis, S.-L. Cai, J. C. Barrett, C. J. Conti, and C. L. Walker (2005)
PNAS
102, 8644-8649
|Abstract »|Full Text »|PDF »
High-Dose Estrogen and Clinical Selective Estrogen Receptor Modulators Induce Growth Arrest, p21, and p53 in Primate Ovarian Surface Epithelial Cells.
J. W. Wright, R. L. Stouffer, and K. D. Rodland (2005)
J. Clin. Endocrinol. Metab.
90, 3688-3695
|Abstract »|Full Text »|PDF »
BRCA2 Regulates Homologous Recombination in Response to DNA Damage: Implications for Genome Stability and Carcinogenesis.
Ductal Lavage of Fluid-Yielding and Non-Fluid-Yielding Ducts in BRCA1 and BRCA2 Mutation Carriers and Other Women at High Inherited Breast Cancer Risk.
A. W. Kurian, M. A. Mills, M. Jaffee, B. M. Sigal, N. M. Chun, K. E. Kingham, L. C. Collins, K. W. Nowels, S. K. Plevritis, J. E. Garber, et al. (2005)
Cancer Epidemiol. Biomarkers Prev.
14, 1082-1089
|Abstract »|Full Text »|PDF »
