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Grant Details

Grant Number: 5R01CA070817-09 Interpret this number
Primary Investigator: Hunter, David
Organization: Brigham And Women'S Hosp., Inc.
Project Title: Cohort Study of Genetic Markers in Colon Cancer
Fiscal Year: 2005
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Abstract

It is proposed to use the resources of three well-characterized cohort studies with prospectively collected blood specimen banks, the Nurses Health Study, the Health Professionals Follow-up Study, and the Physician's Health Study, to prospectively assess gene-nutrient and other gene-environment interactions in the etiology of colorectal cancer and adenomas. The carcinogen- metabolizing genes the investigators will assay are N-acetyltransferase 2, N-acetyltransferase 1, glutathione S-transferase M1 (GSTM1) and CYP1A1. They hypothesize that "fast acetylator" NAT2 genotype, a recently described defect in NAT1, homozygous deletions in the GSTM1 gene, and the "extensive metabolizer" CYP1A1 genotypes are associated with increased risk of colorectal cancer and adenomas. In addition, they will assess interactions of known and suspected colon cancer risk factors with these genotypes, including red meat intake, antioxidant vitamin and carotenoid intake, folate consumption, smoking and alcohol. They expect to identify 604 cases of colorectal cancer and 558 cases of first-adenomatous polyps; each case will be matched by age and race to a control in a nested case-control study. They state they will have greater than 80% power across the three studies to prospectively assess the main effects of these genotypes with colorectal cancer and polyps. They further state that they have substantial power to test for interactions. The investigators state that these studies will be among the first to prospectively test these hypotheses, and provide population-based estimates of attributable risks. They comment that associations with these genotypes would implicate their substrates in cancer etiology, clarifying the specific colon carcinogens in diet. They further comment that identifying gene-diet interactions would suggest dietary interventions that persons with the risk genotypes could make to reduce their risk. They conclude that confirmation of risk genotypes would also be useful in identifying persons at high risk of colon cancer and assist in focusing screening efforts.

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Publications

Dietary folate, alcohol and B vitamins in relation to LINE-1 hypomethylation in colon cancer.
Authors: Schernhammer ES, Giovannucci E, Kawasaki T, Rosner B, Fuchs CS, Ogino S
Source: Gut, 2010 Jun;59(6), p. 794-9.
EPub date: 2009 Oct 14.
PMID: 19828464
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A prospective study of dietary folate and vitamin B and colon cancer according to microsatellite instability and KRAS mutational status.
Authors: Schernhammer ES, Giovannuccci E, Fuchs CS, Ogino S
Source: Cancer Epidemiol Biomarkers Prev, 2008 Oct;17(10), p. 2895-8.
PMID: 18843035
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Folate and vitamin B6 intake and risk of colon cancer in relation to p53 expression.
Authors: Schernhammer ES, Ogino S, Fuchs CS
Source: Gastroenterology, 2008 Sep;135(3), p. 770-80.
EPub date: 2008 Jun 12.
PMID: 18619459
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Association of the TCF7L2 polymorphism with colorectal cancer and adenoma risk.
Authors: Hazra A, Fuchs CS, Chan AT, Giovannucci EL, Hunter DJ
Source: Cancer Causes Control, 2008 Nov;19(9), p. 975-80.
EPub date: 2008 May 14.
PMID: 18478343
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Postmenopausal hormone therapy and stroke: role of time since menopause and age at initiation of hormone therapy.
Authors: Grodstein F, Manson JE, Stampfer MJ, Rexrode K
Source: Arch Intern Med, 2008 Apr 28;168(8), p. 861-6.
PMID: 18443262
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Large-scale evaluation of genetic variants in candidate genes for colorectal cancer risk in the Nurses' Health Study and the Health Professionals' Follow-up Study.
Authors: Hazra A, Chanock S, Giovannucci E, Cox DG, Niu T, Fuchs C, Willett WC, Hunter DJ
Source: Cancer Epidemiol Biomarkers Prev, 2008 Feb;17(2), p. 311-9.
PMID: 18268114
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Plasma folate, vitamin B6, vitamin B12, and homocysteine and pancreatic cancer risk in four large cohorts.
Authors: Schernhammer E, Wolpin B, Rifai N, Cochrane B, Manson JA, Ma J, Giovannucci E, Thomson C, Stampfer MJ, Fuchs C
Source: Cancer Res, 2007 Jun 1;67(11), p. 5553-60.
PMID: 17545639
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p53 Arg72Pro polymorphism and risk of colorectal adenoma and cancer.
Authors: Koushik A, Tranah GJ, Ma J, Stampfer MJ, Sesso HD, Fuchs CS, Giovannucci EL, Hunter DJ
Source: Int J Cancer, 2006 Oct 15;119(8), p. 1863-8.
PMID: 16721787
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O6-methylguanine-DNA methyltransferase Leu84Phe and Ile143Val polymorphisms and risk of colorectal cancer in the Nurses' Health Study and Physicians' Health Study (United States).
Authors: Tranah GJ, Bugni J, Giovannucci E, Ma J, Fuchs C, Hines L, Samson L, Hunter DJ
Source: Cancer Causes Control, 2006 Jun;17(5), p. 721-31.
PMID: 16633920
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Cyclin D1 A870G polymorphism and the risk of colorectal cancer and adenoma.
Authors: Schernhammer ES, Tranah GJ, Giovannucci E, Chan AT, Ma J, Colditz GA, Hunter DJ, Willett WC, Fuchs CS
Source: Br J Cancer, 2006 Mar 27;94(6), p. 928-34.
PMID: 16495921
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Epoxide hydrolase and CYP2C9 polymorphisms, cigarette smoking, and risk of colorectal carcinoma in the Nurses' Health Study and the Physicians' Health Study.
Authors: Tranah GJ, Chan AT, Giovannucci E, Ma J, Fuchs C, Hunter DJ
Source: Mol Carcinog, 2005 Sep;44(1), p. 21-30.
PMID: 15924351
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APC Asp1822Val and Gly2502Ser polymorphisms and risk of colorectal cancer and adenoma.
Authors: Tranah GJ, Giovannucci E, Ma J, Fuchs C, Hunter DJ
Source: Cancer Epidemiol Biomarkers Prev, 2005 Apr;14(4), p. 863-70.
PMID: 15824157
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A prospective study of folate intake and the risk of pancreatic cancer in men and women.
Authors: Skinner HG, Michaud DS, Giovannucci EL, Rimm EB, Stampfer MJ, Willett WC, Colditz GA, Fuchs CS
Source: Am J Epidemiol, 2004 Aug 1;160(3), p. 248-58.
PMID: 15257998
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XRCC2 and XRCC3 polymorphisms are not associated with risk of colorectal adenoma.
Authors: Tranah GJ, Giovannucci E, Ma J, Fuchs C, Hankinson SE, Hunter DJ
Source: Cancer Epidemiol Biomarkers Prev, 2004 Jun;13(6), p. 1090-1.
PMID: 15184273
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A prospective study of plasma C-peptide and colorectal cancer risk in men.
Authors: Ma J, Giovannucci E, Pollak M, Leavitt A, Tao Y, Gaziano JM, Stampfer MJ
Source: J Natl Cancer Inst, 2004 Apr 7;96(7), p. 546-53.
PMID: 15069117
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Epoxide hydrolase polymorphisms, cigarette smoking and risk of colorectal adenoma in the Nurses' Health Study and the Health Professionals Follow-up Study.
Authors: Tranah GJ, Giovannucci E, Ma J, Fuchs C, Hankinson SE, Hunter DJ
Source: Carcinogenesis, 2004 Jul;25(7), p. 1211-8.
EPub date: 2004 Feb 26.
PMID: 14988221
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Employment status, social ties, and caregivers' mental health.
Authors: Cannuscio CC, Colditz GA, Rimm EB, Berkman LF, Jones CP, Kawachi I
Source: Soc Sci Med, 2004 Apr;58(7), p. 1247-56.
PMID: 14759673
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The relationship between a polymorphism in CYP17 with plasma hormone levels and prostate cancer.
Authors: Haiman CA, Stampfer MJ, Giovannucci E, Ma J, Decalo NE, Kantoff PW, Hunter DJ
Source: Cancer Epidemiol Biomarkers Prev, 2001 Jul;10(7), p. 743-8.
PMID: 11440959
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A prospective study of cytochrome P450 1A1 polymorphisms and colorectal cancer risk in men.
Authors: Ishibe N, Stampfer M, Hunter DJ, Hennekens C, Kelsey KT
Source: Cancer Epidemiol Biomarkers Prev, 2000 Aug;9(8), p. 855-6.
PMID: 10952105
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Novel germline mutations in the PTEN tumour suppressor gene found in women with multiple cancers.
Authors: De Vivo I, Gertig DM, Nagase S, Hankinson SE, O'Brien R, Speizer FE, Parsons R, Hunter DJ
Source: J Med Genet, 2000 May;37(5), p. 336-41.
PMID: 10807691
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A prospective study of methylenetetrahydrofolate reductase and methionine synthase gene polymorphisms, and risk of colorectal adenoma.
Authors: Chen J, Giovannucci E, Hankinson SE, Ma J, Willett WC, Spiegelman D, Kelsey KT, Hunter DJ
Source: Carcinogenesis, 1998 Dec;19(12), p. 2129-32.
PMID: 9886567
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A methylenetetrahydrofolate reductase polymorphism and the risk of colorectal cancer.
Authors: Chen J, Giovannucci E, Kelsey K, Rimm EB, Stampfer MJ, Colditz GA, Spiegelman D, Willett WC, Hunter DJ
Source: Cancer Res, 1996 Nov 1;56(21), p. 4862-4.
PMID: 8895734
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