Abstract 3276: Identifying cross-phenotype inflammatory effects in cancer

Abstract

Abstract Through genome-wide association studies we now better understand many of the genetic factors contributing to cancer. However, the overlap between cancer associated loci and inflammation associated loci remains poorly understood. Inflammation has long been considered the underlying basis to several complex traits and plays well-established roles in elevating risk to various cancer types. In fact, genome-wide association studies have identified loci associated with inflammatory biomarkers and risk of cancer. Therefore we sought to test cross-phenotype genetic effects between cancer and inflammation biomarkers. While genome-wide significant loci on their own typically account for very little of the measured narrow-sense heritability, polygenic approaches show greater promise to account for the missing heritability of complex traits. Therefore we built polygenic signatures from inflammatory biomarker genome-wide association studies. Preliminary analysis of a case control pancreatic cancer dataset (304 cases/1425 controls) where we applied seven inflammatory signatures indicates that polygenic scores built from IL-10 and C-reactive protein (CRP) are significant predictors of case control status. Importantly the directions of effect for IL-10 and CRP are consistent with the canonical roles of these proteins. We extended this approach to a breast cancer dataset (1082 cases/1086 controls) where we found that polygenic scores built from CRP are significant predictors of case control status. In both the pancreatic and breast cancer datasets CRP polygenic scores decrease risk of case status. This approach will not only inform us of the cancers with overlapping inflammatory effects, but also allow us to identify the components of the immune system that mediate cancer risk. Ultimately this understanding may lead to the use of anti-inflammatory medication for individuals at risk for a particular cancer. Therefore this research addresses cancer prevention by studying the inflammatory genetic component to risk. Citation Format: Keston Aquino-Michaels, Vasya Trubetskoy, Hae Kyung Im, Nancy Cox. Identifying cross-phenotype inflammatory effects in cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3276. doi:10.1158/1538-7445.AM2014-3276