BRCA1/BRCA2 founder mutations and cancer risks: impact in the western Danish population

Familial Cancer
Henriette Roed NielsenChristina Therkildsen

Abstract

Mutations in the BRCA1 and BRCA2 genes significantly contribute to hereditary breast cancer and ovarian cancer, but the phenotypic effect from different mutations is insufficiently recognized. We used a western Danish clinic-based cohort of 299 BRCA families to study the female cancer risk in mutation carriers and their untested first-degree relatives. Founder mutations were characterized and the risk of cancer was assessed in relation to the specific mutations. In BRCA1, the cumulative cancer risk at age 70 was 35 % for breast cancer and 29 % for ovarian cancer. In BRCA2, the cumulative risk was 44 % for breast cancer and 15 % for ovarian cancer. We identified 47 distinct BRCA1 mutations and 48 distinct mutations in BRCA2. Among these, 8 founder mutations [BRCA1 c.81-?_4986+?del, c.3319G>T (p.Glu1107*), c.3874delT and c.5213G>A (p.Gly1738Glu) and BRCA2 c.6373delA, c.7008-1G>A, c.7617+1G>A and c.8474delC] were found to account for 23 % of the BRCA1 mutations and for 32 % of the BRCA2 mutations. The BRCA1 mutation c.3319G>T was, compared to other BRCA1 mutations, associated with a higher risk for ovarian cancer. In conclusion, founder mutations in BRCA1 and BRCA2 contribute to up to one-third of the families in western Denmark a...Continue Reading

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Citations

Mar 10, 2016·Familial Cancer·Henriette Roed NielsenAnne-Bine Skytte
Jan 18, 2018·Hereditary Cancer in Clinical Practice·Cecilie HerambLovise Mæhle
Mar 29, 2020·Molecular Carcinogenesis·Gabriela Angélica Martínez-NavaLuisa Torres-Sánchez
Mar 23, 2017·Archives of Gynecology and Obstetrics·Cornelia MeiselKarin Kast
Sep 30, 2019·European Journal of Medical Genetics·Neslihan DuzkaleOlcay Kandemir

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