Understanding similarities among phenotypically distinct cancers could provide insight into biological basis of disease and suggest treatment overlap among patients with seemingly distinct cancers. We will evaluate this by undertaking a genome-wide association study (GWAS) across all major cancers types in the genotyped cohort of the Research Program on Genes, Environment and Health. Our aims are to: 1) Undertake an overall cancer GWAS across cancer sites to obtain a baseline estimate of the potential pleiotrophic association of genetic variants with multiple cancers. 2) Apply recently developed cross-site GWAS methods to search for potential associations across varying subgroups of cancers. 3) Extend the approach applied in Aim 2 to consider more complex sets of cancer subtypes. 4) The potential subgroups for consideration in the combined GWAS will be based on germline genetic information. We will develop novel approaches that cluster individuals with cancer into potential subgroups that reflect their genetic similarity.