Abstract LB-161: GAME-ON and OncoArray: Understanding the genetic architecture of cancer risk

Abstract

Abstract Most common cancers develop as a result of complex interactions among environmental exposures and genetic susceptibility variants. Hundreds of common, low penetrance variants have been identified by genetic association studies, and the discovery and subsequent analyses of these variants has led to and will continue to contribute to new insights into cancer risk. The NCI’s Genetic Associations and Mechanisms in Oncology (GAME-ON) initiative was focused on five common cancers - breast, colorectal, lung, prostate, and ovarian - and included three research areas: meta-analysis of GWAS data, functional analysis of genetic susceptibility variants, and clinical and epidemiological studies of these cancer types. As part of GAME-ON, the OncoArray consortium undertook an extensive genotyping effort to enable new discoveries about the genetic architecture and mechanisms underlying several cancer types by discovering new common and rare susceptibility variants through fine-mapping and high density genotyping. The OncoArray data represents a valuable resource for the research community and will enable a wide range of future studies of genetic susceptibility to cancer, including functional annotation of risk loci, analysis of shared heritability across cancers, risk modeling, and analyses of differences in genetic risk attributable to ancestry. The OncoArray consortium was an international effort that accomplished genotyping of over 500K SNPs in over 500K cases of common cancers and cancer-free controls. The cancer types genotyped included the five common cancers from the GAME-ON initiative and several others, such as endometrial, pancreatic cancer, and glioma. SNPs were chosen based on analyses by GAME-ON members and included variants from loci identified in previous association studies, candidate rare variants from whole genome and whole exome sequencing, variants with potential functional significance, and several pharmacogenomics variants. Tagging SNPs that could capture variability for Asian and African descent populations also were included, as were loci of interest to cancer related phenotypes, such as drug metabolism and radiation response. Genotyping was conducted at 8 sites, primarily at the Center for Inherited Disease Research and included QC measures to ensure comparability across genotyping sites. The data are available at the NIH’s Database of Genotypes and Phenotypes (dbGaP). Citation Format: Stefanie A. Nelson, Charlisse Caga-Anan, Danielle Daee, Maura Kate Costello, Daniela Seminara, Christopher I. Amos, Stephen B. Gruber, Christopher Haiman, David Hunter, Peter Kraft, Thomas Sellers, Elizabeth M. Gillanders. GAME-ON and OncoArray: Understanding the genetic architecture of cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-161. doi:10.1158/1538-7445.AM2017-LB-161