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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA112237-03
Application #
7226265
Study Section
Epidemiology of Cancer Study Section (EPIC)
Program Officer
Reid, Britt C
Project Start
2005-07-15
Project End
2010-04-30
Budget Start
2007-05-01
Budget End
2008-04-30
Support Year
3
Fiscal Year
2007
Total Cost
$443,702
Indirect Cost
Name
University of Southern California
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
Schmit, Stephanie L; Figueiredo, Jane C; Cortessis, Victoria K et al. (2015) The Influence of Screening for Precancerous Lesions on Family-Based Genetic Association Tests: An Example of Colorectal Polyps and Cancer. Am J Epidemiol 182:714-22
Levine, A Joan; Win, Aung Ko; Buchanan, Daniel D et al. (2012) Cancer risks for the relatives of colorectal cancer cases with a methylated MLH1 promoter region: data from the Colorectal Cancer Family Registry. Cancer Prev Res (Phila) 5:328-35
Levine, A Joan; Figueiredo, Jane C; Lee, Won et al. (2010) A candidate gene study of folate-associated one carbon metabolism genes and colorectal cancer risk. Cancer Epidemiol Biomarkers Prev 19:1812-21
Figueiredo, Jane C; Levine, A Joan; Lee, Won H et al. (2010) Genes involved with folate uptake and distribution and their association with colorectal cancer risk. Cancer Causes Control 21:597-608
Poynter, Jenny N; Jacobs, Elizabeth T; Figueiredo, Jane C et al. (2010) 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. Cancer Epidemiol Biomarkers Prev 19:525-36
Levine, A Joan; Figueiredo, Jane C; Lee, Won et al. (2010) Genetic variability in the MTHFR gene and colorectal cancer risk using the colorectal cancer family registry. Cancer Epidemiol Biomarkers Prev 19:89-100
Thomas, Duncan C; Conti, David V; Baurley, James et al. (2009) Use of pathway information in molecular epidemiology. Hum Genomics 4:21-42
Poynter, Jenny N; Figueiredo, Jane C; Conti, David V et al. (2007) Variants on 9p24 and 8q24 are associated with risk of colorectal cancer: results from the Colon Cancer Family Registry. Cancer Res 67:11128-32