Association between BRIP1 (BACH1) polymorphisms and breast cancer risk: a meta-analysis

Inconsistency of reported associations between the Pro919Ser polymorphism in the BRCA1 interacting protein 1 (BRIP1) gene and breast cancer prompted us to undertake a meta-analysis. Although investigated by fewer studies, we have also studied the risk associated with the two additional BRIP1 polymorphisms, C47G and G64A, and breast cancer riskWe conducted searches of the published literature in MEDLINE through PubMed up to October 2012. Individual data on 5,122 cases and 5,735 controls from eight published case-control studies were evaluated for the Pro919Ser polymorphism. Accordingly, C47G and G64A polymorphisms were studied in 1,539 cases and 1,183 controls, and 667 and 782, respectively.In the overall analysis, association was lacking between the Pro919Ser polymorphism and breast cancer risk (odds ratio [OR] 0.98-1.02), materially unchanged when confined to subjects of European ancestry (OR 0.96-1.03) or even in the high-powered studies (OR 0.97-1.03). In the menopausal subgroups, premenopausal women followed the null pattern (OR 0.94-0.98) for the Pro and Ser allele contrasts, but not for the Pro-Ser genotype comparison where significant increased risk was observed (OR 1.39, P = 0.002). The postmenopausal women (> 50 years) exhibited a range of pooled effects from protection (OR 0.83, P = 0.11) in the Pro-Ser genotype to slightly increased risk (OR 1.12-1.16, P = 0.28-0.42) in the Pro and Ser allele comparisons. The G64A polymorphism effects were essentially null (OR 0.90-0.98), but C47G was found to confer non-significantly increased risk under all genetic models (OR 1.27-1.40).Upon conclusion, overall summary estimates imply no associations but suggest susceptibility among carriers of the C47G polymorphism and Pro-Ser genotype in premenopausal women. The premenopausal findings and variable outcomes in postmenopausal women require more studies for confirmation.