Assessing Interactions between Common Genetic Variant on 2q35 and Hormone Receptor Status with Breast Cancer Risk: Evidence Based on 26 Studies

Genome-wide association studies have identified 2q35-rs13387042 as a new breast cancer (BC) susceptibility locus in populations of European descent. Since then, the relationship between 2q35-rs13387042 and breast cancer has been reported in various ethnic groups; however, these studies have yielded inconsistent results. To investigate this inconsistency, we performed a meta-analysis of 26 studies involving a total of 101,529 cases and 167,363 controls for 2q35-rs13387042 polymorphism to evaluate its effect on genetic susceptibility for breast cancer. An overall random effects odds ratio of 1.14 (95% CI: 1.11–1.16, P<10(−5)) was found for rs13387042-A variant. Significant results were also observed using dominant (OR = 1.14, 95% CI: 1.12–1.17, P<10(−5)), recessive (OR = 1.17, 95% CI: 1.13–1.21, P<10(−5)) and co-dominant genetic model (heterozygous: OR = 1.15, 95% CI: 1.12–1.19, P<10(−5); homozygous: OR = 1.20, 95% CI: 1.15–1.24, P<10(−5)). There was strong evidence of heterogeneity, which largely disappeared after stratification by ethnicity. Significant associations were found in East Asians, and White populations when stratified by ethnicity; while no significant associations were observed in Africans and other ethnic populations. An association was observed for both ER-positive (OR = 1.17, 95% 1.15–1.19; P<10(−5)) and ER-negative disease (OR = 1.08, 95% CI: 1.04–1.13; P<10(−4)) and both progesterone receptor (PR)-positive (OR = 1.18, 95% CI: 1.15–1.21; P<10(−5)) and PR-negative disease (OR = 1.10, 95% CI: 1.05–1.15; P<10(−4)). In conclusion, this meta-analysis demonstrated that the A allele of 2q35-rs13387042 is a risk factor associated with increased breast cancer susceptibility.