Risk of contralateral breast cancer associated with common variants in BRCA1 and BRCA2: potential modifying effect of BRCA1/BRCA2 mutation carrier status
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Jane C. Figueiredo Jennifer D. Brooks David V. Conti Jenny N. Poynter Sharon N. Teraoka Kathleen E. Malone Leslie Bernstein Won D. Lee
- چاپ و سال / کشور: 2010
Description
Rare deleterious mutations in BRCA1 and BRCA2 are associated with an elevated risk of breast and ovarian cancer. Whether or not common variants in these genes are independently associated with risk of breast cancer remains unclear. In this study, we included 632 Caucasian women with asynchronous contralateral breast cancer (CBC, cases) and 1,221 women with unilateral breast cancer (UBC, controls) from the WECARE (Women’s Environment, Cancer and Radiation Epidemiology) Study. BRCA1 and BRCA2 deleterious mutation status was measured using denaturing high-performance liquid chromatography followed by direct sequencing, yielding including 88 BRCA1 and 60 BRCA2 deleterious mutation carriers. We also genotyped samples on the Illumina Omni1-Quad platform. We assessed the association between CBC risk and common (minor allele frequency (MAF)[0.05) single-nucleotide polymorphisms (SNPs) in BRCA1 (n SNPs = 22) and BRCA2 (n SNPs = 30) and haplotypes using conditional logistic regression accounting for BRCA1/BRCA2 mutation status. We found no significant associations between any single-SNPs or haplotypes of BRCA1 or BRCA2 and risk of CBC among all women. When we stratified by BRCA1 and BRCA2 mutation carrier status, we found suggestive evidence that risk estimates for selected SNPs in BRCA1 (rs8176318, rs1060915, and rs16940) and BRCA2 (rs11571686, rs206115, and rs206117) may differ in noncarriers and carriers of deleterious mutations in BRCA1 and BRCA2. One common haplotype on BRCA1 was inversely significantly associated with risk only among non-BRCA1 and BRCA2 carriers. The association between common variants in BRCA1 and BRCA2 and risk of CBC may differ depending on BRCA1 and BRCA2 mutation carrier status.
Breast Cancer Res Treat (2011) 127:819–829 DOI 10.1007/s10549-010-1285-1 Received: 9 July 2010 / Accepted: 29 November 2010 / Published online: 15 December 2010
