Grant Number:	5R01CA085846-02 Interpret this number
Primary Investigator:	Slattery, Martha
Organization:	University Of Utah
Project Title:	Growth Factors and Colon Cancer
Fiscal Year:	2002

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.




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 00:00:00.0; 128(11), p. 2726-34.
PMID: 20949557
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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.
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 00:00:00.0; 660(1-2), p. 12-21.
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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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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 00:00:00.0; 122(7), p. 1611-7.
PMID: 18059035
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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.
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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.
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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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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 00:00:00.0; 118(12), p. 3140-6.
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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.
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Haplotype Analysis Of Common Vitamin D Receptor Variants And Colon And Rectal Cancers
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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.
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Polymorphisms In Insulin-related Genes Predispose To Specific Kras2 And Tp53 Mutations In Colon Cancer
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Source: Mutation Research, 2006-03-20 00:00:00.0; 595(1-2), p. 117-24.
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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.
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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.
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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.
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Insulin-like growth factor pathway polymorphisms associated with body size in Hispanic and non-Hispanic white women.
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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.
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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 00:00:00.0; 115(1), p. 148-54.
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