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

Grant Number: 5R01CA112237-05 Interpret this number
Primary Investigator: Haile, Robert
Organization: University Of Southern California
Project Title: Folate, Vitamin D and Calcium in Colorectal Cancer
Fiscal Year: 2009
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Abstract

DESCRIPTION (provided by applicant): The Cooperative Family Registry for Colorectal Cancer Studies (Colon CFR) is an NCI-supported consortium dedicated to the establishment of a comprehensive collaborative infrastructure for interdisciplinary studies in the genetics and genetic epidemiology of colorectal cancer. The cooperating institutions are collecting epidemiological information and laboratory specimens from families who represent the continuum of risk for colorectal cancer. A major area of etiological research to which the Colon CFR is committed is candidate gene association studies, where we plan to target selected "pathways", rather than focusing on isolated genes. This application, along with a parallel application submitted by Dr. John Potter, is meant to initiate the Colon CFR research on candidate genes. The Colon CFR has identified three pathways with which to start: folate metabolism and vitamin D/calcium, which are addressed in this application, and the NSAID pathway, which is addressed in Dr. Potter's application. For this application, we have the following specific aims: Folate. Conduct a family-based case-control association study of selected genes that are involved in the metabolism of folate. Our current list of genes of interest includes: serine hydroxymethyltransferase (SHMT1), mehylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), methionine synthase reductase (MTRR), thymidylate synthase (TYMS or TS), S-adenosylhomocysteine hydrolase (AHCY or SAHH), ADA (adenosine deaminase), methionine adenosyl transferase 2A (MAT2A), folate receptor (FOLR1), reduced folate carrier (RFC1 or SLC19A1), S-adenosylmethionine decarboxylase (AMD1), gastric instrinsic factor (GIF), transcobalamin II (TCII), intrinsic factor cobalamin receptor (IFCR), and alcohol dehydrogenase 3 (ADH3). Vitamin D and Calcium. Conduct a family-based case-control association study of selected genes that are involved in the metabolism of vitamin D and calcium. Our current list of genes includes: vitamin D receptor (VDR), retinoid X receptor (RXR), vitamin D binding protein (DBF), calcium sensing receptor (CaSR), and the ileal sodium-dependent bile acid transporter (SLC10A2). Genotyping will primarily involve SNP-based haplotypes. For both pathways, analyses of gene-gene and gene-environment interactions will be included as appropriate.

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Publications

The Influence of Screening for Precancerous Lesions on Family-Based Genetic Association Tests: An Example of Colorectal Polyps and Cancer.
Authors: Schmit S.L. , Figueiredo J.C. , Cortessis V.K. , Thomas D.C. .
Source: American journal of epidemiology, 2015-10-15; 182(8), p. 714-22.
EPub date: 2015-08-24.
PMID: 26306664
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Cancer risks for the relatives of colorectal cancer cases with a methylated MLH1 promoter region: data from the Colorectal Cancer Family Registry.
Authors: Levine A.J. , Win A.K. , Buchanan D.D. , Jenkins M.A. , Baron J.A. , Young J.P. , Long T.I. , Weisenberger D.J. , Laird P.W. , McCall R.L. , et al. .
Source: Cancer prevention research (Philadelphia, Pa.), 2012 Feb; 5(2), p. 328-35.
EPub date: 2011-12-05.
PMID: 22144422
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Use of pathway information in molecular epidemiology.
Authors: Thomas D.C. , Conti D.V. , Baurley J. , Nijhout F. , Reed M. , Ulrich C.M. .
Source: Human genomics, 2009 Oct; 4(1), p. 21-42.
PMID: 21072972
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A candidate gene study of folate-associated one carbon metabolism genes and colorectal cancer risk.
Authors: Levine A.J. , Figueiredo J.C. , Lee W. , Conti D.V. , Kennedy K. , Duggan D.J. , Poynter J.N. , Campbell P.T. , Newcomb P. , Martinez M.E. , et al. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2010 Jul; 19(7), p. 1812-21.
PMID: 20615890
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Genetic variation in the vitamin D receptor (VDR) and the vitamin D-binding protein (GC) and risk for colorectal cancer: results from the Colon Cancer Family Registry.
Authors: Poynter J.N. , Jacobs E.T. , Figueiredo J.C. , Lee W.H. , Conti D.V. , Campbell P.T. , Levine A.J. , Limburg P. , Le Marchand L. , Cotterchio M. , et al. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2010 Feb; 19(2), p. 525-36.
EPub date: 2010-01-19.
PMID: 20086113
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Genetic variability in the MTHFR gene and colorectal cancer risk using the colorectal cancer family registry.
Authors: Levine A.J. , Figueiredo J.C. , Lee W. , Poynter J.N. , Conti D. , Duggan D.J. , Campbell P.T. , Newcomb P. , Martinez M.E. , Hopper J.L. , et al. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2010 Jan; 19(1), p. 89-100.
PMID: 20056627
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Genes involved with folate uptake and distribution and their association with colorectal cancer risk.
Authors: Figueiredo J.C. , Levine A.J. , Lee W.H. , Conti D.V. , Poynter J.N. , Campbell P.T. , Duggan D. , Lewinger J.P. , Martinez M.E. , Ulrich C.M. , et al. .
Source: Cancer causes & control : CCC, 2010 Apr; 21(4), p. 597-608.
EPub date: 2009-12-27.
PMID: 20037791
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Variants on 9p24 and 8q24 are associated with risk of colorectal cancer: results from the Colon Cancer Family Registry.
Authors: Poynter J.N. , Figueiredo J.C. , Conti D.V. , Kennedy K. , Gallinger S. , Siegmund K.D. , Casey G. , Thibodeau S.N. , Jenkins M.A. , Hopper J.L. , et al. .
Source: Cancer research, 2007-12-01; 67(23), p. 11128-32.
PMID: 18056436
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