Colorectal cancer (CRC) is a major cause of cancer deaths in the United States and many other countries. Chronic inflammation has been suggested to play a major role in the pathogenesis of CRC. We propose in this application to conduct a nested case-control study within the Shanghai Women's Health Study, a large population-based prospective cohort study, to evaluate the association of CRC risk with measures of several key products of the inflammatory process and with related genetic markers of inflammation. Specifically, we will include 580 incident cases of CRC and their individually matched controls (1 to1 match for biochemical markers and 1 to 3 match for genetic markers). Urine samples collected at baseline will be measured for a major metabolite of prostaglandin E2 (PGE2) using a liquid chromatographic/mass spectrometric assay and F2-isoprostanes using the mass spectrometric method. Baseline blood samples will be measured for soluble tumor necrosis factor-a receptors, interleukin-6, and C-reactive protein. Genomic DNA will be assayed for polymorphisms in genes involved in PGE2 production (PTGS2, PTGES), metabolism (15-PGDH), and signaling (PTGER1-PTGER4). We will perform statistical analyses to evaluate the associations between these biochemical and genetic markers of inflammation and CRC risk and potential interactions of these markers. Given the large sample size, the prospective study design, the availability of comprehensive baseline survey data and biospecimens, as well as the excellent collaborative environment, we believe that this proposed study represents a unique opportunity to evaluate, vigorously and cost-efficiently, the relationship between various markers of inflammation and CRC. Overall, this study will contribute significantly to the understanding of the role of inflammation in the etiology of CRC and to the development of new strategies for the assessment of CRC risk.
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