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Grant Details

Grant Number: 5R01CA085846-06 Interpret this number
Primary Investigator: Slattery, Marty
Organization: University Of Utah
Project Title: Growth Factors and Colon Cancer
Fiscal Year: 2006
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Abstract

Cell growth and proliferation are central to carcinogenesis. Scientific evidence that growth hormones, and genetic variants that influence these growth hormones, are importantly related to colorectal cancer is increasing. Furthermore, insulin and insulin-like growth factors (IGF), growth hormones that appear to be important for colorectal cancer, are influenced by previously identified risk factors for colorectal cancer such as body size and physical activity. In this study we will use existing lifestyle and metabolic exposure data; known tumor mutational status of microsatellite instability and K-ras mutations; and available germline DNA from an incident colorectal cancer case-control study of approximately 3000 cases and 3000 controls to study how genetic variants that influence growth hormones and cell growth and proliferation relate to development of colorectal cancer and subsequent survival after diagnosis. The study focuses on genetic and environmental interaction. Specific genes examined are molecular variants of genes along insulin pathway, including the IGF1 gene, insulin- like growth factor binding protein-3 (IGFBP3), the insulin receptor substrate gene 1 (IRS-1), the insulin receptor substrate gene-2 (IRS-2); the peroxisome proliferator-activated receptor gamma gene (PPARgamma), apolipoprotein E gene (ApoE), and the vitamin D receptor gene (VDR). We hypothesize that these variants are associated with altered risk of colorectal cancer in conjunction with genetic, diet, and lifestyle factors. Specially, we hypothesize that molecular variants of IGF1, IGFBP3, IRS-1, IRS-2, PPARgamma, ApoE, and VDR interact with dietary such as calcium, vitamin D, sugar, and glycemic index; sunshine exposure, physical activity, aspirin use, and body size to alter risk of colorectal cancer; that molecular variants of IGF1, IGFBP3, IRS-1, IRS-2, PPARgamma, ApoE, and VDR are associated with specific types of mutations in tumors including microsatellite instability and K-ras mutations; and that molecular variants of IGF1, IGFBP3, IRS-1, IRS-2, PPARgamma, ApoE, and VDR are associated with survival after diagnosis. To test the hypothesis that these variants interact with dietary and other factors, it is necessary to have a large sample size, such as the one available. Molecular variants of these genes that are involved in the insulin and growth factor disease pathway will be determined. Statistical analyses will use logistic regression and survival methods. This study builds on a unique existing resource to study genetic and environmental associations with colorectal cancer. It will provide insight into colon cancer etiology and therefore avenues to disease prevention.

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Publications

Genetic variation in C-reactive protein in relation to colon and rectal cancer risk and survival.
Authors: Slattery M.L. , Curtin K. , Poole E.M. , Duggan D.J. , Samowitz W.S. , Peters U. , Caan B.J. , Potter J.D. , Ulrich C.M. .
Source: International journal of cancer, 2011-06-01; 128(11), p. 2726-34.
EPub date: 2010-11-28.
PMID: 20949557
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Assessing tumor mutations to gain insight into base excision repair sequence polymorphisms and smoking in colon cancer.
Authors: Curtin K. , Samowitz W.S. , Wolff R.K. , Ulrich C.M. , Caan B.J. , Potter J.D. , Slattery M.L. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2009 Dec; 18(12), p. 3384-8.
PMID: 19959686
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Vitamin D related genes, CYP24A1 and CYP27B1, and colon cancer risk.
Authors: Dong L.M. , Ulrich C.M. , Hsu L. , Duggan D.J. , Benitez D.S. , White E. , Slattery M.L. , Farin F.M. , Makar K.W. , Carlson C.S. , et al. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2009 Sep; 18(9), p. 2540-8.
EPub date: 2009-08-25.
PMID: 19706847
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Colon tumor mutations and epigenetic changes associated with genetic polymorphism: insight into disease pathways.
Authors: Slattery M.L. , Wolff R.K. , Curtin K. , Fitzpatrick F. , Herrick J. , Potter J.D. , Caan B.J. , Samowitz W.S. .
Source: Mutation research, 2009-01-15; 660(1-2), p. 12-21.
EPub date: 2008-10-15.
PMID: 18992263
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Oncogenetic tree model of somatic mutations and DNA methylation in colon tumors.
Authors: Sweeney C. , Boucher K.M. , Samowitz W.S. , Wolff R.K. , Albertsen H. , Curtin K. , Caan B.J. , Slattery M.L. .
Source: Genes, chromosomes & cancer, 2009 Jan; 48(1), p. 1-9.
PMID: 18767147
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Transcription factor 7-like 2 polymorphism and colon cancer.
Authors: Slattery M.L. , Folsom A.R. , Wolff R. , Herrick J. , Caan B.J. , Potter J.D. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2008 Apr; 17(4), p. 978-82.
PMID: 18398040
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Leptin and leptin receptor genotypes and colon cancer: gene-gene and gene-lifestyle interactions.
Authors: Slattery M.L. , Wolff R.K. , Herrick J. , Caan B.J. , Potter J.D. .
Source: International journal of cancer, 2008-04-01; 122(7), p. 1611-7.
PMID: 18059035
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CDX2 VDR polymorphism and colorectal cancer.
Authors: Slattery M.L. , Herrick J. , Wolff R.K. , Caan B.J. , Potter J.D. , Sweeney C. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2007 Dec; 16(12), p. 2752-5.
PMID: 18086783
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IL6 genotypes and colon and rectal cancer.
Authors: Slattery M.L. , Wolff R.K. , Herrick J.S. , Caan B.J. , Potter J.D. .
Source: Cancer causes & control : CCC, 2007 Dec; 18(10), p. 1095-105.
EPub date: 2007-08-13.
PMID: 17694420
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Vitamin D receptor gene (VDR) associations with cancer.
Authors: Slattery M.L. .
Source: Nutrition reviews, 2007 Aug; 65(8 Pt 2), p. S102-4.
PMID: 17867381
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Associations between vitamin D, vitamin D receptor gene and the androgen receptor gene with colon and rectal cancer.
Authors: Slattery M.L. , Sweeney C. , Murtaugh M. , Ma K.N. , Caan B.J. , Potter J.D. , Wolff R. .
Source: International journal of cancer, 2006-06-15; 118(12), p. 3140-6.
PMID: 16425262
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Haplotype analysis of common vitamin D receptor variants and colon and rectal cancers.
Authors: Sweeney C. , Curtin K. , Murtaugh M.A. , Caan B.J. , Potter J.D. , Slattery M.L. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2006 Apr; 15(4), p. 744-9.
PMID: 16614118
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PPARgamma and colon and rectal cancer: associations with specific tumor mutations, aspirin, ibuprofen and insulin-related genes (United States).
Authors: Slattery M.L. , Curtin K. , Wolff R. , Ma K.N. , Sweeney C. , Murtaugh M. , Potter J.D. , Levin T.R. , Samowitz W. .
Source: Cancer causes & control : CCC, 2006 Apr; 17(3), p. 239-49.
PMID: 16489531
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Polymorphisms in insulin-related genes predispose to specific KRAS2 and TP53 mutations in colon cancer.
Authors: Samowitz W.S. , Wolff R.K. , Ma K.N. , Andersen K. , Caan B. , Slattery M.L. .
Source: Mutation research, 2006-03-20; 595(1-2), p. 117-24.
PMID: 16448675
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Vitamin D receptor gene polymorphisms, dietary promotion of insulin resistance, and colon and rectal cancer.
Authors: Murtaugh M.A. , Sweeney C. , Ma K.N. , Potter J.D. , Caan B.J. , Wolff R.K. , Slattery M.L. .
Source: Nutrition and cancer, 2006; 55(1), p. 35-43.
PMID: 16965239
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Associations between ERalpha, ERbeta, and AR genotypes and colon and rectal cancer.
Authors: Slattery M.L. , Sweeney C. , Murtaugh M. , Ma K.N. , Wolff R.K. , Potter J.D. , Caan B.J. , Samowitz W. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2005 Dec; 14(12), p. 2936-42.
PMID: 16365013
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Associations between apoE genotype and colon and rectal cancer.
Authors: Slattery M.L. , Sweeney C. , Murtaugh M. , Ma K.N. , Potter J.D. , Levin T.R. , Samowitz W. , Wolff R. .
Source: Carcinogenesis, 2005 Aug; 26(8), p. 1422-9.
EPub date: 2005-04-07.
PMID: 15817610
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Insulin-like growth factor pathway polymorphisms associated with body size in Hispanic and non-Hispanic white women.
Authors: Sweeney C. , Murtaugh M.A. , Baumgartner K.B. , Byers T. , Giuliano A.R. , Herrick J.S. , Wolff R. , Caan B.J. , Slattery M.L. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2005 Jul; 14(7), p. 1802-9.
PMID: 16030120
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Energy balance, insulin-related genes and risk of colon and rectal cancer.
Authors: Slattery M.L. , Murtaugh M. , Caan B. , Ma K.N. , Neuhausen S. , Samowitz W. .
Source: International journal of cancer, 2005-05-20; 115(1), p. 148-54.
PMID: 15688407
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Interactions of peroxisome proliferator-activated receptor {gamma} and diet in etiology of colorectal cancer.
Authors: Murtaugh M.A. , Ma K.N. , Caan B.J. , Sweeney C. , Wolff R. , Samowitz W.S. , Potter J.D. , Slattery M.L. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2005 May; 14(5), p. 1224-9.
PMID: 15894676
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The CYP1A1 genotype may alter the association of meat consumption patterns and preparation with the risk of colorectal cancer in men and women.
Authors: Murtaugh M.A. , Sweeney C. , Ma K.N. , Caan B.J. , Slattery M.L. .
Source: The Journal of nutrition, 2005 Feb; 135(2), p. 179-86.
PMID: 15671210
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PPARgamma, energy balance, and associations with colon and rectal cancer.
Authors: Slattery M.L. , Murtaugh M.A. , Sweeney C. , Ma K.N. , Potter J.D. , Caan B.J. , Samowitz W. .
Source: Nutrition and cancer, 2005; 51(2), p. 155-61.
PMID: 15860437
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Associations between BMI, energy intake, energy expenditure, VDR genotype and colon and rectal cancers (United States).
Authors: Slattery M.L. , Murtaugh M. , Caan B. , Ma K.N. , Wolff R. , Samowitz W. .
Source: Cancer causes & control : CCC, 2004 Nov; 15(9), p. 863-72.
PMID: 15577288
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CYP1A1, cigarette smoking, and colon and rectal cancer.
Authors: Slattery M.L. , Samowtiz W. , Ma K. , Murtaugh M. , Sweeney C. , Levin T.R. , Neuhausen S. .
Source: American journal of epidemiology, 2004-11-01; 160(9), p. 842-52.
PMID: 15496536
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Dietary calcium, vitamin D, VDR genotypes and colorectal cancer.
Authors: Slattery M.L. , Neuhausen S.L. , Hoffman M. , Caan B. , Curtin K. , Ma K.N. , Samowitz W. .
Source: International journal of cancer, 2004-09-20; 111(5), p. 750-6.
PMID: 15252846
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Associations among IRS1, IRS2, IGF1, and IGFBP3 genetic polymorphisms and colorectal cancer.
Authors: Slattery M.L. , Samowitz W. , Curtin K. , Ma K.N. , Hoffman M. , Caan B. , Neuhausen S. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2004 Jul; 13(7), p. 1206-14.
PMID: 15247132
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Aspirin, NSAIDs, and colorectal cancer: possible involvement in an insulin-related pathway.
Authors: Slattery M.L. , Samowitz W. , Hoffman M. , Ma K.N. , Levin T.R. , Neuhausen S. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2004 Apr; 13(4), p. 538-45.
PMID: 15066917
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