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National Institutes of Health: National Cancer Institute: Division of Cancer Control and Population Sciences
Grant Details

Grant Number: 5R01CA066794-05 Interpret this number
Primary Investigator: Haile, Robert
Organization: University Of Southern California
Project Title: Gene Environment Interactions in Colorectal Polyps
Fiscal Year: 1998
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Abstract

Our objective is to investigate gene-environment interactions in the etiology of colorectal polyps. We are currently conducting a sigmoidoscopy-based case-control study of polyps. Cases are asymptomatic subjects with a first-time diagnosis of adenomatous polyps. Controls have no history of any polyps and screen negative at sigmoidoscopy. Subjects complete a food frequency questionnaire, an interview regarding physical activity, medicines, including NSAID's, and hormones, and provide a fasting blood sample for analyses of serum nutrient levels. The buffy coat has been saved and we have access to all tumor tissue taken at sigmoidoscopy and colonoscopy. There will be 600 cases and 600 controls by the start of this proposed study. We propose to study the effect of selected metabolic genes on risk of polyps and see whether these genes modify the effects of other exposures. We will focus first on acetylator genotypes (NAT2 polymorphism) and NAT1 and cytochrome P-450 (CYP1A2) phenotypes and their possible modification of the red meat effect, and ApoE and its possible modification of lipid-related exposures. We also plan to study the effect of other genes related to lipoproteins (ApoAII, ApoB, ApoI/CIII, AIV cluster, and LDL receptor), guided somewhat by results with ApoE, and to study glutathione S- transferase and its effect on risk of polyps. Also, as part of Project 3, tumor tissue from polyps cases will be studied for somatic events related to K-ras, APC, DCC, MCC and p53, as well as evidence of genomic instability related to the familial colon cancer (FCC) gene on chromosome 2. The same polyps cases will be studied for involvement (germline or somatic) of the FCC gene after it is cloned and characterized. We propose here to investigate gene-environment interactions involving the oncogenes and tumor suppressor genes listed above. Given that our outcome is polyps, we expect to have greater power to study K-ras and FCC since these are likely to be more common events. This is Project 2. Project 1 is a genetic-epidemiologic study of familial colorectal cancer and Project 3 focusses on the molecular genetics of both colorectal cancer and polyps.

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Publications

A Sigmoidoscopy-based Case-control Study Of Polyps: Macronutrients, Fiber And Meat Consumption
Authors: Haile R.W. , Witte J.S. , Longnecker M.P. , Probst-Hensch N. , Chen M.J. , Harper J. , Frankl H.D. , Lee E.R. .
Source: International Journal Of Cancer, 1997-11-14 00:00:00.0; 73(4), p. 497-502.
PMID: 9389562
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Empiric Assessment Of Parameters That Affect The Design Of Multireader Receiver Operating Characteristic Studies
Authors: Rockette H.E. , Campbell W.L. , Britton C.A. , Holbert J.M. , King J.L. , Gur D. .
Source: Academic Radiology, 1999 Dec; 6(12), p. 723-9.
PMID: 10887893
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A Case-control Study Of Microsomal Epoxide Hydrolase, Smoking, Meat Consumption, Glutathione S-transferase M3, And Risk Of Colorectal Adenomas
Authors: Cortessis V. , Siegmund K. , Chen Q. , Zhou N. , Diep A. , Frankl H. , Lee E. , Zhu Q.S. , Haile R. , Levy D. .
Source: Cancer Research, 2001-03-15 00:00:00.0; 61(6), p. 2381-5.
PMID: 11289100
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An Association Between Genetic Polymorphisms In The Ileal Sodium-dependent Bile Acid Transporter Gene And The Risk Of Colorectal Adenomas
Authors: Wang W. , Xue S. , Ingles S.A. , Chen Q. , Diep A.T. , Frankl H.D. , Stolz A. , Haile R.W. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2001 Sep; 10(9), p. 931-6.
PMID: 11535543
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Glutathione Transferase Gstt1, Broccoli, And Prevalence Of Colorectal Adenomas
Authors: Lin H.J. , Zhou H. , Dai A. , Huang H.F. , Lin J.H. , Frankl H.D. , Lee E.R. , Haile R.W. .
Source: Pharmacogenetics, 2002 Mar; 12(2), p. 175-9.
PMID: 11875371
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Prostaglandin H Synthase 2 Variant (val511ala) In African Americans May Reduce The Risk For Colorectal Neoplasia
Authors: Lin H.J. , Lakkides K.M. , Keku T.O. , Reddy S.T. , Louie A.D. , Kau I.H. , Zhou H. , Gim J.S. , Ma H.L. , Matthies C.F. , et al. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2002 Nov; 11(11), p. 1305-15.
PMID: 12433707
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Hematopoietic Prostaglandin D Synthase (hpgds): A High Stability, Val187ile Isoenzyme Common Among African Americans And Its Relationship To Risk For Colorectal Cancer
Authors: Tippin B.L. , Levine A.J. , Materi A.M. , Song W.L. , Keku T.O. , Goodman J.E. , Sansbury L.B. , Das S. , Dai A. , Kwong A.M. , et al. .
Source: Prostaglandins & Other Lipid Mediators, 2012 Jan; 97(1-2), p. 22-8.
PMID: 21821144
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