title: Population-based screening for breast and ovarian cancer risk due to BRCA1 and BRCA2.
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.
authors.affiliation: Medical Genetics Institute, Shaare Zedek Medical Center, Jerusalem 91031, Israel; Faculty of Medicine, Hebrew University Medical School, Jerusalem 91120, Israel;
authors.forename: Efrat
authors.initials: E
authors.lastname: Gabai-Kapara
authors.affiliation: Faculty of Medicine, Hebrew University Medical School, Jerusalem 91120, Israel; Department of Family Medicine, Clalit Health Services, Jerusalem 91120, Israel;
authors.forename: Amnon
authors.initials: A
authors.lastname: Lahad
authors.affiliation: Institute of Oncology, Sheba Medical Center, Tel Hashomer 52621, Israel;
authors.forename: Bella
authors.initials: B
authors.lastname: Kaufman
authors.affiliation: Susanne Levy Gertner Oncogenetics Unit, Sheba Medical Center, Tel Hashomer 52621, Israel; Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978, Israel;
authors.forename: Eitan
authors.initials: E
authors.lastname: Friedman
authors.affiliation: Institute of Medical Screening, Sheba Medical Center, Tel Hashomer 52621, Israel;
authors.forename: Shlomo
authors.initials: S
authors.lastname: Segev
authors.affiliation: Medical Genetics Institute, Shaare Zedek Medical Center, Jerusalem 91031, Israel;
authors.forename: Paul
authors.initials: P
authors.lastname: Renbaum
authors.affiliation: Medical Genetics Institute, Shaare Zedek Medical Center, Jerusalem 91031, Israel;
authors.forename: Rachel
authors.initials: R
authors.lastname: Beeri
authors.affiliation: Medical Genetics Institute, Shaare Zedek Medical Center, Jerusalem 91031, Israel;
authors.forename: Moran
authors.initials: M
authors.lastname: Gal
authors.affiliation: Medical Genetics Institute, Shaare Zedek Medical Center, Jerusalem 91031, Israel;
authors.forename: Julia
authors.initials: J
authors.lastname: Grinshpun-Cohen
authors.affiliation: Terem Family Medical Center, Jerusalem 92345, Israel;
authors.forename: Karen
authors.initials: K
authors.lastname: Djemal
authors.affiliation: Departments of Medicine and Genome Sciences, University of Washington, Seattle, WA 98195; and.
authors.forename: Jessica B
authors.initials: JB
authors.lastname: Mandell
authors.affiliation: Departments of Medicine and Genome Sciences, University of Washington, Seattle, WA 98195; and.
authors.forename: Ming K
authors.initials: MK
authors.lastname: Lee
authors.affiliation: Department of Obstetrics and Gynecology, Shaare Zedek Medical Center, Jerusalem 91031, Israel.
authors.forename: Uziel
authors.initials: U
authors.lastname: Beller
authors.affiliation: Institute of Oncology, Sheba Medical Center, Tel Hashomer 52621, Israel;
authors.forename: Raphael
authors.initials: R
authors.lastname: Catane
authors.affiliation: Departments of Medicine and Genome Sciences, University of Washington, Seattle, WA 98195; and mcking@u.washington.edu lahad@szmc.org.il.
authors.forename: Mary-Claire
authors.initials: MC
authors.lastname: King
authors.affiliation: 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.
authors.forename: Ephrat
authors.initials: E
authors.lastname: Levy-Lahad
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods*; D005828:Genetics, Population; D006801:Humans; D007557:Israel / Q000453:epidemiology; D007585:Jews / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000235:genetics*; D012307:Risk Factors
keywords: genomics