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Proc Natl Acad Sci U S A. 2014 Sep 30;111(39):14205-10. doi: 10.1073/pnas.1415979111. Epub 2014 Sep 5.

Population-based screening for breast and ovarian cancer risk due to BRCA1 and BRCA2.

Author information

1
Medical Genetics Institute, Shaare Zedek Medical Center, Jerusalem 91031, Israel; Faculty of Medicine, Hebrew University Medical School, Jerusalem 91120, Israel;
2
Faculty of Medicine, Hebrew University Medical School, Jerusalem 91120, Israel; Department of Family Medicine, Clalit Health Services, Jerusalem 91120, Israel;
3
Institute of Oncology, Sheba Medical Center, Tel Hashomer 52621, Israel;
4
Susanne Levy Gertner Oncogenetics Unit, Sheba Medical Center, Tel Hashomer 52621, Israel; Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978, Israel;
5
Institute of Medical Screening, Sheba Medical Center, Tel Hashomer 52621, Israel;
6
Medical Genetics Institute, Shaare Zedek Medical Center, Jerusalem 91031, Israel;
7
Terem Family Medical Center, Jerusalem 92345, Israel;
8
Departments of Medicine and Genome Sciences, University of Washington, Seattle, WA 98195; and.
9
Department of Obstetrics and Gynecology, Shaare Zedek Medical Center, Jerusalem 91031, Israel.
10
Departments of Medicine and Genome Sciences, University of Washington, Seattle, WA 98195; and mcking@u.washington.edu lahad@szmc.org.il.
11
Medical Genetics Institute, Shaare Zedek Medical Center, Jerusalem 91031, Israel; Faculty of Medicine, Hebrew University Medical School, Jerusalem 91120, Israel; mcking@u.washington.edu lahad@szmc.org.il.

Abstract

In the Ashkenazi Jewish (AJ) population of Israel, 11% of breast cancer and 40% of ovarian cancer are due to three inherited founder mutations in the cancer predisposition genes BRCA1 and BRCA2. For carriers of these mutations, risk-reducing salpingo-oophorectomy significantly reduces morbidity and mortality. Population screening for these mutations among AJ women may be justifiable if accurate estimates of cancer risk for mutation carriers can be obtained. We therefore undertook to determine risks of breast and ovarian cancer for BRCA1 and BRCA2 mutation carriers ascertained irrespective of personal or family history of cancer. Families harboring mutations in BRCA1 or BRCA2 were ascertained by identifying mutation carriers among healthy AJ males recruited from health screening centers and outpatient clinics. Female relatives of the carriers were then enrolled and genotyped. Among the female relatives with BRCA1 or BRCA2 mutations, cumulative risk of developing either breast or ovarian cancer by age 60 and 80, respectively, were 0.60 (± 0.07) and 0.83 (± 0.07) for BRCA1 carriers and 0.33 (± 0.09) and 0.76 (± 0.13) for BRCA2 carriers. Risks were higher in recent vs. earlier birth cohorts (P = 0.006). High cancer risks in BRCA1 or BRCA2 mutation carriers identified through healthy males provide an evidence base for initiating a general screening program in the AJ population. General screening would identify many carriers who are not evaluated by genetic testing based on family history criteria. Such a program could serve as a model to investigate implementation and outcomes of population screening for genetic predisposition to cancer in other populations.

KEYWORDS:

genomics

PMID:
25192939
PMCID:
PMC4191771
DOI:
10.1073/pnas.1415979111
[Indexed for MEDLINE]
Free PMC Article

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