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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA122364-03
Application #
7683832
Study Section
Special Emphasis Panel (ZRG1-HOP-N (03))
Program Officer
Nelson, Stefanie A
Project Start
2007-09-20
Project End
2011-07-31
Budget Start
2009-08-01
Budget End
2010-07-31
Support Year
3
Fiscal Year
2009
Total Cost
$291,650
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
Spracklen, Cassandra N; Chen, Peng; Kim, Young Jin et al. (2017) Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels. Hum Mol Genet 26:1770-1784
Luu, Hung N; Wen, Wanqing; Li, Honglan et al. (2015) Are dietary antioxidant intake indices correlated to oxidative stress and inflammatory marker levels? Antioxid Redox Signal 22:951-9
Hwang, Joo-Yeon; Sim, Xueling; Wu, Ying et al. (2015) Genome-wide association meta-analysis identifies novel variants associated with fasting plasma glucose in East Asians. Diabetes 64:291-8
Wu, Sheng Hui; Shu, Xiao Ou; Milne, Ginger et al. (2015) Uric acid correlates to oxidation and inflammation in opposite directions in women. Biomarkers 20:225-31
He, Meian; Xu, Min; Zhang, Ben et al. (2015) Meta-analysis of genome-wide association studies of adult height in East Asians identifies 17 novel loci. Hum Mol Genet 24:1791-800
Wen, Wanqing; Zheng, Wei; Okada, Yukinori et al. (2014) Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index. Hum Mol Genet 23:5492-504
Zhang, Ben; Jia, Wei-Hua; Matsuo, Keitaro et al. (2014) Genome-wide association study identifies a new SMAD7 risk variant associated with colorectal cancer risk in East Asians. Int J Cancer 135:948-55
Zhang, Ben; Jia, Wei-Hua; Matsuda, Koichi et al. (2014) Large-scale genetic study in East Asians identifies six new loci associated with colorectal cancer risk. Nat Genet 46:533-42
Qi, Qibin; Kilpeläinen, Tuomas O; Downer, Mary K et al. (2014) FTO genetic variants, dietary intake and body mass index: insights from 177,330 individuals. Hum Mol Genet 23:6961-72
Jiang, Yu; Wu, Sheng-Hui; Shu, Xiao-Ou et al. (2014) Cruciferous vegetable intake is inversely correlated with circulating levels of proinflammatory markers in women. J Acad Nutr Diet 114:700-8.e2

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