Genome-wide association analysis in East Asians identifies breast cancer susceptibility loci at 1q32.1, 5q14.3 and 15q26.1

Abstract

In a three-stage genome-wide association study among East Asian women including 22,780 cases and 24,181 controls, we identified 3 genetic loci newly associated with breast cancer risk, including rs4951011 at 1q32.1 (in intron 2 of the ZC3H11A gene; P=8.82×10(-9)), rs10474352 at 5q14.3 (near the ARRDC3 gene; P=1.67×10(-9)) and rs2290203 at 15q26.1 (in intron 14 of the PRC1 gene; P=4.25×10(-8)). We replicated these associations in 16,003 cases and 41,335 controls of European ancestry (P=0.030, 0.004 and 0.010, respectively). Data from the ENCODE Project suggest that variants rs4951011 and rs10474352 might be located in an enhancer region and transcription factor binding sites, respectively. This study provides additional insights into the genetics and biology of breast cancer.

Figure 1. Forest plots for risk variants in the three newly identified breast cancer risk loci by study site and stage

Per-allele ORs are presented. The size of the box is proportional to the number of cases and controls in each study. (a): rs4951011, (b): rs10474352, (c): rs2290203.

Figure 2. Regional plots of association results for the three newly identified risk loci for breast cancer

For each plot, the −log₁₀ (P values) (y axis) of SNPs are shown according to their chromosomal positions (x axis) in NCBI Build 36. The color of SNPs represents their LD (r², HapMap Asian) with the index SNP at each locus. With the exception of the index SNPs, which are shown as purple diamonds for Stage 1 and purple circles for the meta-analyses of all studies, data shown for all other SNPs are from Stage 1 only. (a): rs4951011 (1q32.1), (b): rs10474352 (5q14.3), (c): rs2290203 (15q26.1).