Breast and Ovarian Cancer Risks Due to Inherited Mutations in BRCA1 and BRCA2
Abstract
Risks of breast and ovarian cancer were determined for Ashkenazi Jewish women with inherited mutations in the tumor suppressor genes BRCA1 and BRCA2 . We selected 1008 index cases, regardless of family history of cancer, and carried out molecular analysis across entire families. The lifetime risk of breast cancer among female mutation carriers was 82%, similar to risks in families with many cases. Risks appear to be increasing with time: Breast cancer risk by age 50 among mutation carriers born before 1940 was 24%, but among those born after 1940 it was 67%. Lifetime risks of ovarian cancer were 54% for BRCA1 and 23% for BRCA2 mutation carriers. Physical exercise and lack of obesity in adolescence were associated with significantly delayed breast cancer onset.
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The lifetime risk of developing breast cancer in BRCA1/2 mutation carriers ranges from 45 to 80%.
“the lifetime risk of developing breast cancer in BRCA1/2 mutation carriers ranges from 45 to 80% [8–11]”
From Fear of cancer recurrence in breast cancer survivors carrying a BRCA1 or 2 genetic mutation : a cross-sectional study (2024) · cites this paper as [10]
Cites
The Statistical Analysis of Failure Time Data.
Aitkin, M. A., Kalbfleisch, J. D., & Prentice, R. L. (1981) · Biometrics · doi:10.2307/2530581 · Cited by 9,875 · see citing works
Antoniou, A., Pharoah, P. D. P., Narod, S., Risch, H. A., Eyfjord, J. E., Hopper, J. L., Loman, N., Olsson, H., Johannsson, O., Borg, Å., et al. (2003) · The American Journal of Human Genetics · doi:10.1086/375033 · Cited by 3,680 · see citing works
Ford, D., Easton, D., Stratton, M. R., Narod, S., Goldgar, D., Devilee, P., Bishop, D., Weber, B., Lenoir, G., Chang-Claude, J., et al. (1998) · American Journal of Human Genetics · doi:10.1086/301749 · Cited by 2,766 · see citing works
The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews.
Struewing, J., Hartge, P., Wacholder, S., Baker, S. M., Berlin, M., McAdams, M., Timmerman, M. M., Brody, L., & Tucker, M. A. (1997) · New England Journal of Medicine · doi:10.1056/nejm199705153362001 · Cited by 2,399 · see citing works
Prophylactic Oophorectomy in Carriers of BRCA1 or BRCA2 Mutations
Rebbeck, T. R., Lynch, H. T., Neuhausen, S. L., Narod, S. A., Veer, L. V., Garber, J. E., Evans, D. G., Isaacs, C. J., Daly, M. B., Matloff, E. T., et al. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa012158 · Cited by 1,462 · see citing works
Risk-Reducing Salpingo-oophorectomy in Women with aBRCA1orBRCA2Mutation
Kauff, N. D., Satagopan, J. M., Robson, M. E., Scheuer, L., Hensley, M. L., Hudis, C. A., Ellis, N. A., Boyd, J. A., Borgen, P. I., Barakat, R. R., et al. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa020119 · Cited by 1,250 · see citing works
Risch, H. A., McLaughlin, J. R., Cole, D. E. C., Rosen, B. P., Bradley, L., Kwan, E., Jack, E., Vesprini, D., Kuperstein, G., Abrahamson, J., et al. (2001) · The American Journal of Human Genetics · doi:10.1086/318787 · Cited by 985 · see citing works
Meijers-Heijboer, H., van Geel, B., van Putten, W. L. J., Henzen-Logmans, S. C., Seynaeve, C., Menke-Pluymers, M. B. E., Bartels, C. C. M., Verhoog, L. C., van den Ouweland, A. M. W., Niermeijer, M. F., et al. (2001) · New England Journal of Medicine · doi:10.1056/nejm200107193450301 · Cited by 973 · see citing works
Frank, T. S. (2002) · Journal of Clinical Oncology · doi:10.1200/jco.20.6.1480 · Cited by 813 · see citing works
Cancer risk estimates for BRCA1 mutation carriers identified in a risk evaluation program.
Brose, M., Rebbeck, T., Calzone, K., Stopfer, J., Nathanson, K., & Weber, B. (2002) · Journal of the National Cancer Institute · doi:10.1093/jnci/94.18.1365 · Cited by 772 · see citing works
Efficacy of Bilateral Prophylactic Mastectomy in BRCA1 and BRCA2 Gene Mutation Carriers
Hartmann, L. C., Sellers, T. A., Schaid, D. J., Frank, T. S., Soderberg, C. L., Sitta, D. L., Frost, M. H., Grant, C. S., Donohue, J. H., Woods, J. E., et al. (2001) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/93.21.1633 · Cited by 743 · see citing works
Anglian Breast Cancer Study Group (2000) · British Journal of Cancer · doi:10.1054/bjoc.2000.1407 · Cited by 602 · see citing works
Frank, T. S., Deffenbaugh, A. M., Reid, J., Hulick, M., Ward, B. E., Lingenfelter, B., Gumpper, K. L., Scholl, T., Tavtigian, S. V., Pruss, D., et al. (2002) · Journal of Clinical Oncology · doi:10.1200/jco.2002.20.6.1480 · Cited by 557 · see citing works
Warner, E., Foulkes, W., Goodwin, P., Meschino, W., Blondal, J., Paterson, C., Ozçelik, H., Goss, P., Allingham-Hawkins, D., Hamel, N., et al. (1999) · Journal of the National Cancer Institute · doi:10.1093/jnci/91.14.1241 · Cited by 421 · see citing works
Outcome of Preventive Surgery and Screening for Breast and Ovarian Cancer in BRCA Mutation Carriers
Scheuer, L. (2002) · Journal of Clinical Oncology · doi:10.1200/jco.20.5.1260 · Cited by 404 · see citing works
Oddoux, C., Struewing, J. P., Clayton, C. M., Neuhausen, S. L., Brody, L. C., Kaback, M. M., Haas, B. R., Norton, L., Borgen, P. I., Jhanwar, S. C., et al. (1996) · Nature Genetics · doi:10.1038/ng1096-188 · Cited by 381 · see citing works
Population-based study of risk of breast cancer in carriers of BRCA2 mutation
Thorlacius, S., Struewing, J. P., Hartage, P., Ólafsdóttir, G. H., Sigvaldason, H., Tryggvadóttír, L., Wacholder, S., Tulinius, H., & Eyfjord, J. E. (1998) · The Lancet · doi:10.1016/s0140-6736(98)03300-5 · Cited by 348 · see citing works
Levy‐Lahad, E., Catane, R., Eisenberg, S., Kaufman, B., Hornreich, G., Lishinsky, E., Shohat, M., Weber, B., Beller, U., Lahad, A., et al. (1997) · Europe PMC (PubMed Central) · Cited by 316 · see citing works
Outcome of Preventive Surgery and Screening for Breast and Ovarian Cancer in BRCA Mutation Carriers
Scheuer, L., Kauff, N. D., Robson, M. E., Kelly, B. N., Barakat, R. R., Satagopan, J. M., Ellis, N. A., Hensley, M. L., Boyd, J. A., Borgen, P. I., et al. (2002) · Journal of Clinical Oncology · doi:10.1200/jco.2002.20.5.1260 · Cited by 239 · see citing works
Fodor, F., Weston, A., Bleiweiss, I., McCurdy, L. D., Walsh, M., Tartter, P., Brower, S., & Eng, C. (1998) · American Journal of Human Genetics · doi:10.1086/301903 · Cited by 236 · see citing works
On the use of familial aggregation in population-based case probands for calculating penetrance.
Begg, C. (2002) · Journal of the National Cancer Institute · doi:10.1093/jnci/94.16.1221 · Cited by 226 · see citing works
The lifetime risks of breast cancer in Ashkenazi Jewish carriers of BRCA1 and BRCA2 mutations.
Satagopan, J. M., Offit, K., Foulkes, W. D., Robson, M. E., Wacholder, S., Eng, C. M., Karp, S. E., & Begg, C. B. (2001) · PubMed · Cited by 218 · see citing works
Modifiers of risk of hereditary breast and ovarian cancer
Narod, S. A. (2002) · Nature reviews. Cancer · doi:10.1038/nrc726 · Cited by 179 · see citing works
Risk Factors for Breast Cancer According to Family History of Breast Cancer
Colditz, G. A., ROSNER, B. A., & Speizer, F. E. (1996) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/88.6.365 · Cited by 166 · see citing works
Ovarian cancer risk in Ashkenazi Jewish carriers of BRCA1 and BRCA2 mutations.
Satagopan, J. M., Boyd, J. A., Kauff, N. D., Robson, M. E., Scheuer, L., Narod, S. A., & Offit, K. (2002) · PubMed · Cited by 152 · see citing works
Effect of family history, obesity and exercise on breast cancer risk among postmenopausal women
Carpenter, C. L., Ross, R. K., Paganini‐Hill, A., & Bernstein, L. (2003) · International Journal of Cancer · doi:10.1002/ijc.11186 · Cited by 145 · see citing works
McGee, T. L., Devoto, M., Ott, J., Berson, E. L., & Dryja, T. P. (1997) · The American Journal of Human Genetics · doi:10.1086/301614 · Cited by 106 · see citing works
Change in the penetrance of founder BRCA1/2 mutations? A retrospective cohort study
Foulkes, W. D., Brunet, J.-S., Wong, N., et al. (2002) · Journal of Medical Genetics · doi:10.1136/jmg.39.6.407 · Cited by 13 · see citing works
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Cited by
Sorted by citations
Cell-cycle checkpoints and cancer
Kastan, M. B., & Bartek, J. (2004) · Nature · doi:10.1038/nature03097 · Cited by 2,836 · see citing works
Meta-Analysis of <i>BRCA1</i> and <i>BRCA2</i> Penetrance
Chen, S., & Parmigiani, G. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2006.09.1066 · Cited by 1,802 · see citing works
Gene–environment interactions in psychiatry: joining forces with neuroscience
Caspi, A., & Moffitt, T. E. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1925 · Cited by 1,300 · see citing works
State-of-the-art strategies for targeting the DNA damage response in cancer
Pilié, P. G., Tang, C., Mills, G. B., & Yap, T. A. (2019) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-018-0114-z · Cited by 1,189 · see citing works
Rebbeck, T. R., Kauff, N. D., & Domchek, S. M. (2009) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djn442 · Cited by 939 · see citing works
Homologous Recombination Deficiency: Exploiting the Fundamental Vulnerability of Ovarian Cancer
Konstantinopoulos, P. A., Ceccaldi, R., Shapiro, G. I., & D'Andrea, A. D. (2015) · Cancer Discovery · doi:10.1158/2159-8290.cd-15-0714 · Cited by 945 · see citing works
Homologous Recombination and Human Health: The Roles of BRCA1, BRCA2, and Associated Proteins
Prakash, R., Zhang, Y., Feng, W., & Jasin, M. (2015) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a016600 · Cited by 869 · see citing works
Meindl, A., Hellebrand, H., Wiek, C., Erven, V., Wappenschmidt, B., Niederacher, D., Freund, M., Lichtner, P., Hartmann, L., Schaal, H., et al. (2010) · Nature Genetics · doi:10.1038/ng.569 · Cited by 743 · see citing works
Contralateral Breast Cancer Risk in <i>BRCA1</i> and <i>BRCA2</i> Mutation Carriers
Graeser, M. K., Engel, C., Rhiem, K., Gadzicki, D., Bick, U., Kast, K., Froster, U. G., Schlehe, B., Bechtold, A., Arnold, N., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.19.9430 · Cited by 314 · see citing works
Multifactorial contributions to an acute DNA damage response by BRCA1/BARD1-containing complexes
Greenberg, R. A., Sobhian, B., Pathania, S., Cantor, S. B., Nakatani, Y., & Livingston, D. M. (2006) · Genes & Development · doi:10.1101/gad.1381306 · Cited by 308 · see citing works
Xie, H., Ma, K., Zhang, K., Zhou, J., Li, L., Yang, W., Gong, Y., Cai, L., & Gong, K. (2021) · Cell Death & Disease · doi:10.1038/s41419-020-03229-8 · Cited by 155 · see citing works
Heemskerk-Gerritsen, B. A. M., Brekelmans, C. T. M., Menke-Pluymers, M. B. E., van Geel, A. N., Tilanus-Linthorst, M. M. A., Bartels, C. C. M., Tan, M., Meijers-Heijboer, H. E. J., Klijn, J. G. M., & Seynaeve, C. (2007) · Annals of Surgical Oncology · doi:10.1245/s10434-007-9449-x · Cited by 153 · see citing works
Insulin-like growth factor (IGF) axis in cancerogenesis
Kasprzak, A., Kwasniewski, W., Adamek, A., & Gozdzicka-Jozefiak, A. (2017) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2016.08.007 · Cited by 130 · see citing works
EMBRACE, Rebbeck, T. R., HEBON, Friebel, T. M., Mitra, N., Wan, F., Chen, S., Andrulis, I. L., Apostolou, P., Arnold, N., et al. (2016) · Breast Cancer Research · doi:10.1186/s13058-016-0768-3 · Cited by 71 · see citing works
Development of Exercise as Interception Therapy for Cancer: A Review
Iyengar, N. M., & Jones, L. W. (2019) · JAMA Oncology · doi:10.1001/jamaoncol.2019.2585 · Cited by 67 · see citing works
Nikkilä, J., Coleman, K. A., Morrissey, D., Pylkäs, K., Erkko, H., Messick, T. E., Karppinen, S.-M., Amelina, A., Winqvist, R., & Greenberg, R. A. (2009) · Oncogene · doi:10.1038/onc.2009.33 · Cited by 63 · see citing works
Surgical risk reduction: Prophylactic salpingo-oophorectomy and prophylactic mastectomy
Dowdy, S. C., Stefanek, M., & Hartmann, L. C. (2004) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2004.04.028 · Cited by 61 · see citing works
Vitamin D/vitamin D receptor axis regulates DNA repair during oncogene-induced senescence
Graziano, S., Johnston, R., Deng, O., Zhang, J., & Gonzalo, S. (2016) · Oncogene · doi:10.1038/onc.2016.77 · Cited by 60 · see citing works
Wei, L., Lan, L., Yasui, A., Tanaka, K., Saijo, M., Matsuzawa, A., Kashiwagi, R., Maseki, E., Hu, Y., Parvin, J. D., et al. (2011) · Cancer Science · doi:10.1111/j.1349-7006.2011.02037.x · Cited by 48 · see citing works
van den Broek, A. J., de Ruiter, K., van 't Veer, L. J., Tollenaar, R. A. E. M., van Leeuwen, F. E., Verhoef, S., & Schmidt, M. K. (2015) · European Journal of Human Genetics · doi:10.1038/ejhg.2014.161 · Cited by 18 · see citing works
Schmidt, M. K., Vermeulen, E., Tollenaar, R. A. E. M., Veer, L. J. V., & Leeuwen, F. E. V. (2009) · European Journal of Cancer · doi:10.1016/j.ejca.2009.03.008 · Cited by 12 · see citing works
Michel, A., Dorval, M., Chiquette, J., & Savard, J. (2024) · Hereditary Cancer in Clinical Practice · doi:10.1186/s13053-024-00285-5 · Cited by 3 · see citing works
- Authors
- King, M.-C., Marks, J. H., & Mandell, J. B.
- Affiliations
- Albert Einstein College of Medicine (US)
- Corresponding author
- King, Mary-Claire
- Mandell, Jessica B.
- Venue
- Science
- Published
- 2003-10-24
- Volume
- 302
- Issue
- 5645
- Pages
- 643-646
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2087025655
- Cited by
- 2,229
- References
- 28
- Citations by year
- 2026: 34 · 2025: 49 · 2024: 54 · 2023: 94 · 2022: 85 · 2021: 94 · 2020: 111 · 2019: 99 · 2018: 102 · 2017: 112 · 2016: 118 · 2015: 140 · 2014: 120 · 2013: 116 · 2012: 127
- FWCI
- 46.86
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Health Sciences › Medicine › Epidemiology › Multiple and Secondary Primary Cancers
- Health Sciences › Medicine › Oncology › Cancer Risks and Factors
- Keywords
- BRCA1, BRCA2, hereditary breast cancer, hereditary ovarian cancer, lifetime cancer risk, Ashkenazi Jewish women, mutation carriers, family history (medicine), physical activity, adolescent obesity, age at cancer onset
- MeSH terms
- Alleles, Breast Neoplasms, Family, Fathers, Female, Genotype, Heterozygote, Humans, Jews, Life Style, Male, Mutation, Obesity, Ovarian Neoplasms, Risk, Time Factors, Cohort Studies, Exercise, Incidence, Age of Onset, Risk Assessment, Genes, BRCA1, Penetrance, Genetic Predisposition to Disease, Genes, BRCA2
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