Familial clustering of site-specific cancer risks associated with BRCA1 and BRCA2 mutations in the Ashkenazi Jewish population
- 28 February 2006
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 103 (10), 3770-3774
- https://doi.org/10.1073/pnas.0511301103
Abstract
Inherited mutations in BRCA1 and BRCA2 lead to significantly increased risks of breast and ovarian cancer. We used epidemiologic methods to evaluate the relative risks of breast cancer vs. ovarian cancer among women of Ashkenazi Jewish ancestry with inherited mutations in BRCA1 or BRCA2. The cancer of a family's index case (i.e., breast cancer vs. ovarian cancer) was significantly associated with site-specific risks of cancer in relatives known to carry mutations in BRCA1 or BRCA2. Specifically, breast cancer risks were higher among relatives of breast cancer index cases compared with relatives of ovarian cancer index cases [hazard ratio (HR) = 3.0, P < 0.001 for BRCA1 carriers and HR = 4.8, P = 0.017 for BRCA2 carriers], and ovarian cancer risks were higher among relatives of ovarian cancer index cases compared with relatives of breast cancer index cases (HR = 7.2, P = 0.001 for BRCA1 carriers and HR = 15.8, P = 0.018 for BRCA2 carriers). Breast and ovarian cancer risks also increased with more recent year of birth. For each later decade of birth, risk increased 1.2-fold (P = 0.03). Effects of cancer site of the index case and of birth cohort were independent. These results suggest that both genetic and nongenetic factors modify cancer risks among BRCA1 and BRCA2 mutation carriers, and that genetic modifiers and other familial factors may influence risk specifically for either breast or ovarian cancer.Keywords
This publication has 25 references indexed in Scilit:
- Younger birth cohort correlates with higher breast and ovarian cancer risk in EuropeanBRCA1 mutation carriersHuman Mutation, 2005
- Breast and ovarian cancer risks to carriers of the BRCA1 5382insC and 185delAG and BRCA2 6174delT mutations: a combined analysis of 22 population based studiesJournal of Medical Genetics, 2005
- Prevention and Management of Hereditary Breast CancerJournal of Clinical Oncology, 2005
- Polyglutamine repeat length in theAIB1 gene modifies breast cancer susceptibility inBRCA1 carriersInternational Journal of Cancer, 2003
- Breast and Ovarian Cancer Risks Due to Inherited Mutations in BRCA1 and BRCA2Science, 2003
- Average Risks of Breast and Ovarian Cancer Associated with BRCA1 or BRCA2 Mutations Detected in Case Series Unselected for Family History: A Combined Analysis of 22 StudiesAmerican Journal of Human Genetics, 2003
- Androgen receptor CAG repeat length in Jewish Israeli women who are BRCA1/2 mutation carriers: association with breast/ovarian cancer phenotypeEuropean Journal of Human Genetics, 2002
- Modifiers of risk of hereditary breast and ovarian cancerNature Reviews Cancer, 2002
- BRCA1 and BRCA2 founder mutations in patients with bilateral breast cancerEuropean Journal of Human Genetics, 1999
- Evidence That the Penetrance of Mutations at the RP11 Locus Causing Dominant Retinitis Pigmentosa Is Influenced by a Gene Linked to the Homologous RP11 AlleleAmerican Journal of Human Genetics, 1997