A subset of the data that support the findings of this study is publically available via dbGaP www. Breast cancer risk is influenced by rare coding variants in susceptibility genes such as BRCA1 and many common, mainly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. We report results from a genome-wide association study GWAS of breast cancer in , cases and , controls of European ancestry and 14, cases and 13, controls of East Asian ancestry 1. The majority of credible risk SNPs in the new loci fall in distal regulatory elements, and by integrating in-silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all SNPs in regulatory features was fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites.
Association analysis identifies 65 new breast cancer risk loci
The 6q There have been conflicting reports about the association of this locus with breast cancer in Europeans, and a GWAS in Europeans identified a different SNP, tagged here by rs We examined the associations of both SNPs in up to 61, cases and 58, controls from forty-four studies collaborating in the Breast Cancer Association Consortium, of which four studies were of Asian and 39 of European descent. Both SNPs are significantly associated with breast cancer risk in both ethnic groups.
Many groups are conducting studies with the aim of identifying genes that may be related to the risk of breast cancer. The aim of the consortium is to combine data from many studies, and to provide a reliable assessment of the risks associated with these genes. The aim of CIMBA is to provide sufficient sample sizes to allow large scale studies in order to evaluate reliably the effects of genetic modifiers.
Breast cancer affects more than , women per year in the EU and causes more than 90, deaths. Identification of women at high risk of the disease can lead to disease prevention through intensive screening, chemoprevention or prophylactic surgery. Breast cancer risk is determined by a combination of genetic and lifestyle risk factors. The advent of next generation sequencing has opened up the opportunity for testing in many disease genes, and diagnostic gene panel testing is being introduced in many EU countries. However, the cancer risks associated with most variants in most genes are unknown.