JC virus (JCV), a common polyomavirus infection in humans, has been proposed as a potential risk factor for colorectal cancer. Several lines of laboratory evidence support a role for JCV in the early development of colorectal cancer. Unfortunately, there have been no epidemiologic studies of the association between past infection with JCV and colorectal cancer. We propose to conduct a matched case-control study of circulating prediagnostic antibodies to JCV and incident colorectal cancer nested within two community- based cohorts in Washington County, MD. The goal of this research is to characterize the relationship between infection with JC virus and colorectal cancer, so that future prevention strategies may be developed. Specifically, our aims are to measure prediagnostic serum antibody levels to JCV capsid and oncoproteins in 582 cases of colorectal cancer, 135 cases of pre-cancerous adenomatous polyps, and 1,299 matched controls, to determine the association between JCV antibody serostatus and subsequent colorectal cancer risk overall and across intervals of induction period, and to investigate longitudinal changes in JCV antibody levels as a predictor of subsequent colorectal cancer development. We hypothesize that JCV is involved in the early stages of colorectal carcinogenesis, and that prediagnostic antibodies to JCV will be associated with increased risk of subsequent colorectal cancer and adenomatous polyps, particularly among cases diagnosed several years after blood draw. Finally, we hypothesize that serologic markers of chronic active JCV infection, namely, a rise in JCV antibody levels over a 15-year period, IgA seropositivity, a Th2 antibody profile (lgG4>lgG1 and 3), and antibodies to JCVT-antigen will be associated with increased risk of subsequent CRC/polyps. Our proposed study is innovative in that it will incorporate immunologic markers of JCV infection measured years prior to colorectal cancer/polyp diagnosis, including six different antibodies to JCV proteins. The Washington Co. cohorts are a unique setting in which to investigate the role of JCV infection in early stages of colorectal cancer development, given that blood samples were obtained and stored up to 30 years prior to cancer diagnosis, and for a subset individuals, blood was obtained at two time points, 15 years apart. This study is highly cost-efficient, since archived samples will be used. Furthermore, study findings will be of great potential public health significance, as JCV could be a novel target for the prevention of colorectal cancer, the third most common cancer among humans. ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ?
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