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

Abstract

We carried out a genome-wide association study among Chinese women to identify risk variants for breast cancer. After analyzing 607,728 SNPs in 1,505 cases and 1,522 controls, we selected 29 SNPs for a fast-track replication in an independent set of 1,554 cases and 1,576 controls. We further investigated four replicated loci in a third set of samples comprising 3,472 cases and 900 controls. SNP rs2046210 at 6q25.1, located upstream of the gene encoding estrogen receptor alpha (ESR1), showed 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 x 10(-15)) in the pooled analysis of samples from all three stages. We also found a similar, albeit weaker, association in an independent study comprising 1,591 cases and 1,466 controls of European ancestry (P(trend) = 0.01). These results strongly implicate 6q25.1 as a susceptibility locus for breast cancer.

Figure 1

Genome-wide association results in the Shanghai Breast Cancer Study, Scatter plot of P-values in log-scale from the trend test for 607,728 genotyped SNPs comparing 1,505 cases and 1,522 controls

Figure 2

Regional plot of chromosome 6q25.1 locus. Results (-logP) are shown for directly genotyped (diamonds) and imputed (circles) SNPs for the region of 151.5–152.5 Mb, flanking 500kb of SNP rs2046210. SNP rs2046210 is shown in blue. Gene locations are from the March 2006 UCSC genome browser assembly. The lower panel shows estimates of pairwise r² for common SNPs (with MAF ≥ 5%) from the HapMap release 23a for the Asian population for the region of 151.9–152.1 Mb, flanking 100 kb of SNP rs2046210.