Abstract 2853: Genetic variation in IGF1, GHR, and IGFBP1 is associated with colorectal cancer

Background The insulin-like growth factor (IGF-1)/growth hormone (GH) pathway has been implicated in the development of colorectal cancer. Circulating IGF-1 increases cell proliferation and inhibits apoptosis. Genetic variation in the IGF pathway genes has been shown to alter circulating IGF-1 concentrations and has been associated with colorectal cancer. This risk may differ by anatomic location. Methods We used a principal components approach to evaluate the relationship between genetic variation in six IGF pathway genes (IGF1, IGF2, IGFBP1, IGFBP3, GHR, and GH1) and colorectal cancer in a family-based case-control study from the Colon Cancer Family Registry (CCFR). Cases were recruited from both high-risk clinics and population-based registries. Controls had no previous diagnosis of colorectal cancer and were full biologic siblings of the cases. Clinic-based (cases = 268, controls = 475) and population-based (cases = 1,802, controls = 2,874) data were analyzed separately and all models were adjusted for age and sex. Results There was no overall association between genetic variation in the IGF pathway genes and colorectal cancer. However, when the data were analyzed by colorectal cancer anatomic location, GH1 was associated with distal colon cancer (p=0.05) in the population-based families and IGF1 was associated with rectal cancer (p=0.004) in the clinic-based families. Furthermore, when the data were stratified by MSI-status, IGFBP1 was associated with MSI-low/stable tumors (p=0.017) in the clinic-based families. Conclusion In this family-based case-control study, genetic variation in IGF1, GHR, and IGFBP1 was associated with colorectal cancer differentially by anatomic location, population source, and tumor type. The clinic-based data represent families with high genetic risk in contrast to the population-based data which represent families of moderate to average genetic risk. These results replicate prior case-only analyses that suggest IGF1 is a modifier of colorectal cancer risk in high-risk families. Single SNP analyses and exploration of SNP x SNP interactions may further elucidate the significance of IGF pathway genes on colorectal cancer risk. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2853.