Functional polymorphisms in the BRCA1 promoter influence transcription and are associated with decreased risk for breast cancer in Chinese women

摘要: Background: The BRCA1 gene is an important breast cancer susceptibility gene. Promoter polymorphisms can alter the binding affinity of transcription factors, changing transcriptional activity and may affect to disease. Methods Results: By direct sequencing promoter region, we identified four c.-2804T>C (rs799908:T>C), c.-2265C>T (rs11655505:C>T), c.-2004A>G (rs799906:A>G) c.-1896(ACA) 1 /(ACA) 2 (rs8176071:(ACA) ) present in Hong Kong Chinese. Each was studied independently combination by functional assays. While all variants significantly altered activity, c.-2265T allele most clearly provided stronger than C common mutant haplotype which contains increased 70%. Risk association first tested cases age-matched controls Chinese women replicated a large population-based study Shanghai Chinese, altogether totaling over 3,000 subjects, demonstrated carriers had reduced risk for (combined ORs=0.80, 95%CI=0.69-0.93; p=0.003) more evident among aged ≥45 years at diagnosis without family history ORs=0.75, 95%CI=0.61-0.91; p=0.004). containing also showed significant (ORs=0.64, 95%CI=0.46-0.89; p=0.008). Conclusion: Our comprehensive with contribution from c.-2265C>T, could population. Its significance other populations remains be investigated.