Evaluating the breast cancer predisposition role of rare variants in genes associated with low-penetrance breast cancer risk SNPs

Abstract

Background: Genome-wide association studies (GWASs) have identified numerous single-nucleotide polymorphisms (SNPs) associated with small increases in breast cancer risk. Studies to date suggest that some SNPs alter the expression of the associated genes, which potentially mediates risk modification. On this basis, we hypothesised that some of these genes may be enriched for rare coding variants associated with a higher breast cancer risk. Methods: The coding regions and exon-intron boundaries of 56 genes that have either been proposed by GWASs to be the regulatory targets of the SNPs and/or located < 500 kb from the risk SNPs were sequenced in index cases from 1043 familial breast cancer fa..