Genome-wide association study identifies a novel breast cancer susceptibility locus at 6q25.1

A genome-wide association study was conducted among Chinese women to identify risk variants for breast cancer. By analyzing 607,728 SNPs in 1505 cases and 1522 controls, we selected 29 promising SNPs for a fast-track replication in an independent set of 1554 cases and 1576 controls. Four replicated loci were further investigated in a third set of samples including 3472 cases and 900 controls. SNP rs2046210 at 6q25.1, located upstream of the estrogen receptor 1 gene (ESR1), exhibited strong and consistent association with breast cancer across all three stages. Adjusted odds ratio (95% CI) were 1.36 (1.24–1.49) and 1.59 (1.40–1.82), respectively, for genotypes A/G and A/A versus G/G (P for trend, 2.0×10(−15)) in the pooled analysis of samples from all three stages. A similar, although weaker, association was also found in an independent study including 1591 cases and 1466 controls of European ancestry (P(trend), 0.01). These results provide strong evidence implicating 6q25.1 as a susceptibility locus for breast cancer.