Single Nucleotide Polymorphism 8q24 rs13281615 and Risk of Breast Cancer: Meta-Analysis of More than 100,000 Cases

Background: The onset and progression of breast cancer (BC) is influenced by many factors, including the single nucleotide polymorphism (SNP) rs13281615 at 8q24. However, studies of the potential association between rs13281615 at 8q24 and risk of BC have given inconsistent results. We performed a meta-analysis to address this controversy. Methods: PubMed, EMBASE and the Chinese National Knowledge Infrastructure databases were systematically searched to identify relevant studies. Two curators independently extracted data, and odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated to assess the strength of the association between rs13281615 at 8q24 and risk of BC. Results: Fourteen studies are included in the meta-analysis, involving 44,283 cases (5,170 Chinese and 39,113 mixed) and 55,756 controls (5,589 Chinese and 50,167 mixed). The GG and G-allele genotypes of rs13281615 at 8q24 are significantly associated with increased risk of BC (GG vs. AG+AA, OR 1.13, 95% CI 1.08-1.19, P<0.001; G-allele vs. A-allele, OR 1.10, 95% CI 1.06-1.14, P<0.001; GG vs. AA, OR 1.20, 95% CI 1.12-1.29, P<0.001). Conversely, the AA genotype is significantly associated with decreased risk of BC (AA vs. AG+GG, OR 0.89, 95% CI 0.84-0.93, P<0.001). Conclusion: G-allele genotypes of rs13281615 at 8q24 polymorphism are a risk factor for developing BC, while the AA genotype is a protective factor. Further large and well-designed studies are required to confirm this conclusion.