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Genome-wide association studies (GWAS) have identified 2q35 and 16q12 as breast cancer (BC) susceptibility loci. However, the association between the two polymorphisms and BC remains controversial and inconsistent. We therefore performed a more precise estimation of these relationships by meta-analysing the currently available evidence from the literature. The PubMed, Ovid, Medline and Web of Science databases were searched. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strengths of the associations. Thirty studies, including 106,312 cases and 140,939 controls, were identified. Overall, significantly elevated breast cancer risk was associated with the A allele of 2q35 rs13387042 when all studies were pooled into the meta-analysis (OR 1.11, 95%CI 1.07-1.15). Additionally, the T allele of 16q12 rs3803662 was associated with significantly increased breast cancer risk (OR 1.20, 95%CI 1.16-1.24). When stratifying for ethnicity, significantly increased risks were found among Caucasians, Asians and mixed ethnicities for both rs13387042 and rs3803662. For rs13387042, an association was observed for both oestrogen receptor-positive (ER+) (OR 1.14, 95%CI 1.11-1.17) and ER-negative (ER-) disease (OR 1.05, 95%CI 1.01-1.09) and for progesterone receptor-positive (PR+) (OR 1.16, 95%CI 1.12-1.19) and PR-negative (PR-) disease (OR 1.07, 95%CI 1.03-1.12). Similarly, a stronger association was observed for rs3803662 with ER+ tumors (OR 1.23, 95%CI 1.13-1.32) compared with ER- tumors (OR 1.08, 95%CI 0.97-1.20), and the same condition occurred for the polymorphism with PR+ tumors (OR 1.26, 95%CI 1.02-1.55) versus with PR- tumors (OR 1.15, 95%CI 0.90-1.46). When stratified by BRCA mutation status, a stronger association was observed with BRCA2 carriers (OR 1.23, 95%CI 1.05-1.44) than BRCA1 carriers (OR 1.09, 95%CI 1.04-1.15). In conclusion, this meta-analysis demonstrated that the A allele of 2q35 rs13387042 and the T allele of 16q12 rs3803662 are risk factors associated with increased breast cancer susceptibility.

Assessing the interactions between the associations of common genetic variants on 2q35 and 16q12 with breast cancer risk