Genome-wide association study identifies a common variant in RAD51B associated with male breast cancer risk

Abstract

We conducted a genome-wide association study of male breast cancer comprising 823 cases and 2,795 controls of European ancestry, with validation in independent sample sets totaling 438 cases and 474 controls. A SNP in RAD51B at 14q24.1 was significantly associated with male breast cancer risk (P = 3.02 × 10(-13); odds ratio (OR) = 1.57). We also refine association at 16q12.1 to a SNP within TOX3 (P = 3.87 × 10(-15); OR = 1.50).

Figure 1. Association and recombination plots for the 14q24.1 and 16q12.1 loci

Directly genotyped SNPs from the discovery phase are represented as diamonds and imputed SNPs as circles. A larger diamond indicates the GWAS “hit” in each region. The strength of linkage disequilibrium between each SNP and the GWAS hit is indicated by the colour intensity of the symbol, from white (r² = 0) to dark red (r² = 1). Recombination rates, plotted in dark blue, are based on the HapMap CEU samples and genomic coordinates are based on NCBI build 36 of the human genome. Results are shown for the (a) 14q24.1 and (b) 16q12.1 loci. The location of rs999737 is indicated in bold at the distal end of RAD51B in the 14q24.1 plot.