Contribution of female breast cancer predisposition SNPs to risk of male breast cancer

Genome-wide association studies have identified more than 170 loci that confer susceptibility to breast cancer. Male breast cancer accounts for approximately 1% off all newly diagnosed cases of breast cancer and several reports have implicated germline genetic factors as significant in the aetiology of the disease. Inherited germline mutations in the BRCA2 gene are thought to account for up to 10% of cases. Here we demonstrate that there are substantial overlaps between polygenic susceptibility to male and female breast cancer and that a subset of shared predisposition loci confer significantly larger risk effects in males than in females. Men in the highest quintile of the distribution of risk allele count have a 2.7-fold (2.17-3.30) increased risk of breast cancer compared to those in the lowest quintile. Furthermore, comparisons of the risk allele distributions in male and female cases suggests that the overall impact of genetic predisposition to breast cancer may be greater in a susceptible minority of males from the general population than in females.