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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