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Grant Details

Grant Number: 5R01CA122364-04 Interpret this number
Primary Investigator: Yang, Gong
Organization: Vanderbilt University
Project Title: Inflammatory Biomarkers and Colorectal Cancer Risk
Fiscal Year: 2010
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Abstract

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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Publications

Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels.
Authors: Spracklen C.N. , Chen P. , Kim Y.J. , Wang X. , Cai H. , Li S. , Long J. , Wu Y. , Wang Y.X. , Takeuchi F. , et al. .
Source: Human molecular genetics, 2017-05-01; 26(9), p. 1770-1784.
PMID: 28334899
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Are dietary antioxidant intake indices correlated to oxidative stress and inflammatory marker levels?
Authors: Luu H.N. , Wen W. , Li H. , Dai Q. , Yang G. , Cai Q. , Xiang Y.B. , Gao Y.T. , Zheng W. , Shu X.O. .
Source: Antioxidants & redox signaling, 2015-04-10; 22(11), p. 951-9.
EPub date: 2015-02-27.
PMID: 25602689
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Meta-analysis of genome-wide association studies of adult height in East Asians identifies 17 novel loci.
Authors: He M. , Xu M. , Zhang B. , Liang J. , Chen P. , Lee J.Y. , Johnson T.A. , Li H. , Yang X. , Dai J. , et al. .
Source: Human molecular genetics, 2015-03-15; 24(6), p. 1791-800.
EPub date: 2014-11-26.
PMID: 25429064
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Uric acid correlates to oxidation and inflammation in opposite directions in women.
Authors: Wu S.H. , Shu X.O. , Milne G. , Xiang Y.B. , Zhang X. , Cai Q. , Fazio S. , Linton M.F. , Chen H. , Purdue M. , et al. .
Source: Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals, 2015; 20(4), p. 225-31.
PMID: 26301880
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Genome-wide association meta-analysis identifies novel variants associated with fasting plasma glucose in East Asians.
Authors: Hwang J.Y. , Sim X. , Wu Y. , Liang J. , Tabara Y. , Hu C. , Hara K. , Tam C.H. , Cai Q. , Zhao Q. , et al. .
Source: Diabetes, 2015 Jan; 64(1), p. 291-8.
EPub date: 2014-09-03.
PMID: 25187374
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FTO genetic variants, dietary intake and body mass index: insights from 177,330 individuals.
Authors: Qi Q. , Kilpeläinen T.O. , Downer M.K. , Tanaka T. , Smith C.E. , Sluijs I. , Sonestedt E. , Chu A.Y. , Renström F. , Lin X. , et al. .
Source: Human molecular genetics, 2014-12-20; 23(25), p. 6961-72.
EPub date: 2014-08-07.
PMID: 25104851
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Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index.
Authors: Wen W. , Zheng W. , Okada Y. , Takeuchi F. , Tabara Y. , Hwang J.Y. , Dorajoo R. , Li H. , Tsai F.J. , Yang X. , et al. .
Source: Human molecular genetics, 2014-10-15; 23(20), p. 5492-504.
EPub date: 2014-05-26.
PMID: 24861553
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Genome-wide association study identifies a new SMAD7 risk variant associated with colorectal cancer risk in East Asians.
Authors: Zhang B. , Jia W.H. , Matsuo K. , Shin A. , Xiang Y.B. , Matsuda K. , Jee S.H. , Kim D.H. , Cheah P.Y. , Ren Z. , et al. .
Source: International journal of cancer, 2014-08-15; 135(4), p. 948-55.
EPub date: 2014-01-29.
PMID: 24448986
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Large-scale genetic study in East Asians identifies six new loci associated with colorectal cancer risk.
Authors: Zhang B. , Jia W.H. , Matsuda K. , Kweon S.S. , Matsuo K. , Xiang Y.B. , Shin A. , Jee S.H. , Kim D.H. , Cai Q. , et al. .
Source: Nature genetics, 2014 Jun; 46(6), p. 533-42.
EPub date: 2014-05-18.
PMID: 24836286
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Cruciferous vegetable intake is inversely correlated with circulating levels of proinflammatory markers in women.
Authors: Jiang Y. , Wu S.H. , Shu X.O. , Xiang Y.B. , Ji B.T. , Milne G.L. , Cai Q. , Zhang X. , Gao Y.T. , Zheng W. , et al. .
Source: Journal of the Academy of Nutrition and Dietetics, 2014 May; 114(5), p. 700-8.e2.
EPub date: 2014-03-13.
PMID: 24630682
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Nonexercise physical activity and inflammatory and oxidative stress markers in women.
Authors: Wu S.H. , Shu X.O. , Chow W.H. , Xiang Y.B. , Zhang X. , Li H.L. , Cai Q. , Milne G. , Ji B.T. , Cai H. , et al. .
Source: Journal of women's health (2002), 2014 Feb; 23(2), p. 159-67.
EPub date: 2013-10-29.
PMID: 24168102
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Body weight, fat distribution and colorectal cancer risk: a report from cohort studies of 134255 Chinese men and women.
Authors: Li H. , Yang G. , Xiang Y.B. , Zhang X. , Zheng W. , Gao Y.T. , Shu X.O. .
Source: International journal of obesity (2005), 2013 Jun; 37(6), p. 783-9.
PMID: 22986684
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Identification of Genetic Susceptibility Loci for Colorectal Tumors in a Genome-Wide Meta-analysis.
Authors: Peters U. , Jiao S. , Schumacher F.R. , Hutter C.M. , Aragaki A.K. , Baron J.A. , Berndt S.I. , Bézieau S. , Brenner H. , Butterbach K. , et al. .
Source: Gastroenterology, 2013 Apr; 144(4), p. 799-807.e24.
EPub date: 2012-12-22.
PMID: 23266556
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Genome-wide association analyses in East Asians identify new susceptibility loci for colorectal cancer.
Authors: Jia W.H. , Zhang B. , Matsuo K. , Shin A. , Xiang Y.B. , Jee S.H. , Kim D.H. , Ren Z. , Cai Q. , Long J. , et al. .
Source: Nature genetics, 2013 Feb; 45(2), p. 191-6.
EPub date: 2012-12-23.
PMID: 23263487
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Soy food consumption and lung cancer risk: a meta-analysis using a common measure across studies.
Authors: Wu S.H. , Liu Z. .
Source: Nutrition and cancer, 2013; 65(5), p. 625-32.
PMID: 23859029
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Adiposity and fat distribution in relation to inflammation and oxidative stress in a relatively lean population of Chinese women.
Authors: Wu S.H. , Shu X.O. , Chow W.H. , Xiang Y.B. , Zhang X. , Cai Q. , Li H.L. , Milne G. , Wen W. , Ji B.T. , et al. .
Source: Disease markers, 2013; 34(4), p. 279-93.
PMID: 23396296
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Soy food intake and circulating levels of inflammatory markers in Chinese women.
Authors: Wu S.H. , Shu X.O. , Chow W.H. , Xiang Y.B. , Zhang X. , Li H.L. , Cai Q. , Ji B.T. , Cai H. , Rothman N. , et al. .
Source: Journal of the Academy of Nutrition and Dietetics, 2012 Jul; 112(7), p. 996-1004, 1004.e1-4.
PMID: 22889631
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Green tea consumption and colorectal cancer risk: a report from the Shanghai Men's Health Study.
Authors: Yang G. , Zheng W. , Xiang Y.B. , Gao J. , Li H.L. , Zhang X. , Gao Y.T. , Shu X.O. .
Source: Carcinogenesis, 2011 Nov; 32(11), p. 1684-8.
EPub date: 2011-08-19.
PMID: 21856996
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Dietary glycemic load and risk of colorectal cancer in Chinese women.
Authors: Li H.L. , Yang G. , Shu X.O. , Xiang Y.B. , Chow W.H. , Ji B.T. , Zhang X. , Cai H. , Gao J. , Gao Y.T. , et al. .
Source: The American journal of clinical nutrition, 2011 Jan; 93(1), p. 101-7.
EPub date: 2010-10-20.
PMID: 20962156
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Isothiocyanate exposure, glutathione S-transferase polymorphisms, and colorectal cancer risk.
Authors: Yang G. , Gao Y.T. , Shu X.O. , Cai Q. , Li G.L. , Li H.L. , Ji B.T. , Rothman N. , Dyba M. , Xiang Y.B. , et al. .
Source: The American journal of clinical nutrition, 2010 Mar; 91(3), p. 704-11.
EPub date: 2009-12-30.
PMID: 20042523
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Prospective cohort study of soy food intake and colorectal cancer risk in women.
Authors: Yang G. , Shu X.O. , Li H. , Chow W.H. , Cai H. , Zhang X. , Gao Y.T. , Zheng W. .
Source: The American journal of clinical nutrition, 2009 Feb; 89(2), p. 577-83.
EPub date: 2008-12-10.
PMID: 19073792
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