A second generation genome-wide association study in breast cancer. (360G-Wellcome-084712_Z_08_Z)

At the current time, approximately 25% of the genetic risk of breast cancer is explained by a combination of rare, high or moderate penetrance genes and common, low penetrance variants. Existing evidence suggests that much of the residual risk is mediated by many, possibly hundreds, of common variants that each confers a small increase in risk. The key goal of this research is to conduct a genome-wide association study to identify such breast cancer susceptibility alleles. In the first stage, 4,000 genetically enriched breast cancer cases and matched controls will be typed for 550,000 SNPs using the Illumina Infinium Duo 550k array, and genotypes will be compared with existing data on the 550k array available from the 1958 birth cohort. Associations identified in this genome-wide experiment will then be followed up in further stages involving a large, international consortium of an additional 40,000 breast cancer cases and 40,000 controls. Power calculations indicate that this design will identify most common variants that each explain at least 0.2% of the familial risk of the disease. Together, these detectable variants may explain much of the genetic variance of breast cancer.