A Genome-wide association study in childhood kidney cancer (Wilms tumor) . (360G-Wellcome-088804_Z_09_Z)

At the current time, only a small proportion of the genetic risk of Wilms tumor is explained by known factors. It is likely that much of the residual risk is mediated by common variants that each confers a modest increase in risk. Our key goal is to conduct a genome-wide association scan to identify such Wilms tumor susceptibility alleles. In the GWAS, 2000 Wilms tumor cases will be genotyped for 660000 SNPs and genotypes will be compared with existing data on 6500 geographically-matched con trols. Any loci showing strong evidence of association after the GWAS will be fast-tracked for immediate verification by Taqman. Additionally, we will test 1536 SNPs from the ~1000 regions showing the strongest associations in 2000 additional cases using a custom assay. These genotypes will be compared to data available on an additional 6500 geographically-matched controls. Power calculations indicate we have at least 80% power to identify any locus conferring a per-allele risk of 1.25, pro viding the allele frequency is at least 20%. By additionally genotyping DNA from both parents of 1000 cases, we will investigate parent-of-origin effects for all confirmed loci and the 150kb critical region involved in control of IGF2 imprinting.