Association between a novel polymorphism (rs2046210) of the 6q25.1 locus and breast cancer risk

The novel single nucleotide polymorphism (SNP), rs2046210, was identified in a breast cancer genome-wide association study of Chinese women. The SNP is located on 6q25.1 in proximity to the C6orf97 and estrogen receptor 1 (ESR1) genes. To replicate this susceptibility, a number of case-control studies have been conducted in various populations. However, some results were inconclusive due to the restriction of sample size or ethnic diversity. To derive a more precise estimation of the relationship between rs2046210 and genetic risk of breast cancer, we performed the first comprehensive meta-analysis which included 121,494 cases and 119,295 controls from 14 published studies. Overall, significant increased risk between the A allele of rs2046210 and breast cancer was found in the total population (allelic model: OR = 1.16, 95 %CI = 1.11-1.21, P (heterogeneity) < 0.0001; dominant model: OR = 1.22, 95 %CI = 1.14-1.29, P (heterogeneity) < 0.0001; recessive model: OR = 1.21, 95 %CI = 1.13-1.29, P (heterogeneity) < 0.0001). When stratified by ethnicity, significant elevated risk was found among Europeans and Asians. However, no significant association was detected in African descent population. In the subgroup analyses according to estrogen receptor (ER) positive/negative status, our results suggested that this polymorphism tended to increase breast cancer risk in ER negative tumors by a greater magnitude compared to ER positive tumors. In addition, our subgroup analysis also indicated that this SNP was significantly associated with the risk of breast cancer for BRCA1 mutation carriers and exhibited weaker association with the risk for BRCA2 mutation carriers. Substantial heterogeneity was present in the overall analysis, but largely disappeared after stratification by ethnicity. Despite some limitations, this meta-analysis demonstrates that the rs2046210 polymorphism may be a risk factor associated with increased breast cancer risk. However, the association varies in different ethnicities.