Quantitative assessment of the association between rs2046210 at 6q25.1 and breast cancer risk

Genome-wide association studies (GWAS) have identified several genetic susceptibility loci for breast cancer (BC). One of them, conducted among Chinese women, found an association of rs2046210 at 6q25.1 with the risk of BC recently. Since then, numerous association studies have been carried out to investigate the relationship between this polymorphism and BC risk in various populations. However, these have yielded contradictory results. We therefore performed a meta-analysis to clarify this inconsistency. Overall, a total of 235003 subjects based on 13 studies were included in our study. Significantly increased BC risk was detected in the pooled analysis [allele contrast: OR = 1.13, 95%CI = 1.10-1.17, P(Z) <10(-5), P(Q) <10(-4); dominant model: OR = 1.21, 95%CI = 1.14-1.27, P(Z) <10(-5), P(Q) <10(-4); recessive model: OR = 1.18, 95%CI = 1.12-1.24, P(Z) <10(-5), P(Q) = 0.04]. In addition, our data revealed that rs2046210 conferred greater risk in estrogen receptor (ER)-negative tumors [OR = 1.27, 95%CI = 1.15-1.40, P(Z) <10(-5), P(Q) <10(-4)] than in ER-positive ones [OR = 1.18, 95%CI = 1.09-1.28, P(Z) <10(-4), P(Q) = 0.0003]. When stratified by ethnicity, significant associations were found in Caucasian and Asian populations, but not detected among Africans. There was evidence of heterogeneity (P<0.05), however, the heterogeneity largely disappeared after stratification by ethnicity. The present meta-analysis demonstrated that the rs2046210 polymorphism may be associated with increased BC susceptibility, but this association varies in different ethnicities.