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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

Cancer risks for the relatives of colorectal cancer cases with a methylated MLH1 promoter region: data from the Colorectal Cancer Family Registry.
Authors: Levine AJ, Win AK, Buchanan DD, Jenkins MA, Baron JA, Young JP, Long TI, Weisenberger DJ, Laird PW, McCall RL, Duggan DJ, Haile RW
Source: Cancer Prev Res (Phila), 2012 Feb;5(2), p. 328-35.
EPub date: 2011 Dec 5.
PMID: 22144422
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Use of pathway information in molecular epidemiology.
Authors: Thomas DC, Conti DV, Baurley J, Nijhout F, Reed M, Ulrich CM
Source: Hum 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 AJ, Figueiredo JC, Lee W, Conti DV, Kennedy K, Duggan DJ, Poynter JN, Campbell PT, Newcomb P, Martinez ME, Hopper JL, Le Marchand L, Baron JA, Limburg PJ, Ulrich CM, Haile RW
Source: Cancer Epidemiol Biomarkers Prev, 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 JN, Jacobs ET, Figueiredo JC, Lee WH, Conti DV, Campbell PT, Levine AJ, Limburg P, Le Marchand L, Cotterchio M, Newcomb PA, Potter JD, Jenkins MA, Hopper JL, Duggan DJ, Baron JA, Haile RW
Source: Cancer Epidemiol Biomarkers Prev, 2010 Feb;19(2), p. 525-36.
EPub date: 2010 Jan 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 AJ, Figueiredo JC, Lee W, Poynter JN, Conti D, Duggan DJ, Campbell PT, Newcomb P, Martinez ME, Hopper JL, Le Marchand L, Baron JA, Limburg PJ, Ulrich CM, Haile RW
Source: Cancer Epidemiol Biomarkers Prev, 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 JC, Levine AJ, Lee WH, Conti DV, Poynter JN, Campbell PT, Duggan D, Lewinger JP, Martinez ME, Ulrich CM, Newcomb P, Potter J, Limburg PJ, Hopper J, Jenkins MA, Le Marchand L, Baron JA, Haile RW
Source: Cancer Causes Control, 2010 Apr;21(4), p. 597-608.
EPub date: 2009 Dec 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 JN, Figueiredo JC, Conti DV, Kennedy K, Gallinger S, Siegmund KD, Casey G, Thibodeau SN, Jenkins MA, Hopper JL, Byrnes GB, Baron JA, Goode EL, Tiirikainen M, Lindor N, Grove J, Newcomb P, Jass J, Young J, Potter JD, Haile RW, Duggan DJ, Le Marchand L, Colon CFR
Source: Cancer Res, 2007 Dec 1;67(23), p. 11128-32.
PMID: 18056436
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