Folate, Vitamin D and Calcium in Colorectal Cancer

Summary

Principal Investigator: Robert Haile
Abstract: 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.
Funding Period: 2005-07-15 - 2010-04-30
more information: NIH RePORT

Top Publications

  1. pmc Genes involved with folate uptake and distribution and their association with colorectal cancer risk
    Jane C Figueiredo
    Department of Preventive Medicine, Keck School of Medicine, University of Southern California, 1450 Biggy Street Room 1509J, Los Angeles, CA 90033, USA
    Cancer Causes Control 21:597-608. 2010
  2. pmc 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
    Jenny N Poynter
    Department of Preventive Medicine, University of Southern California, Los Angeles, California, USA
    Cancer Epidemiol Biomarkers Prev 19:525-36. 2010
  3. pmc A candidate gene study of folate-associated one carbon metabolism genes and colorectal cancer risk
    A Joan Levine
    USC Keck School of Medicine, Department of Preventive Medicine, Genetic Epidemiology, NRT 1450 Biggy Street Room 1509A, Los Angeles, CA 90033, USA
    Cancer Epidemiol Biomarkers Prev 19:1812-21. 2010
  4. pmc Use of pathway information in molecular epidemiology
    Duncan C Thomas
    Department of Preventive Medicine, University of Southern California, 1540 Alcazar St, CHP 220, Los Angeles, CA 90089 9011, USA
    Hum Genomics 4:21-42. 2009
  5. pmc Cancer risks for the relatives of colorectal cancer cases with a methylated MLH1 promoter region: data from the Colorectal Cancer Family Registry
    A Joan Levine
    Department of Preventive Medicine, Genetic Epidemiology, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA
    Cancer Prev Res (Phila) 5:328-35. 2012
  6. ncbi Variants on 9p24 and 8q24 are associated with risk of colorectal cancer: results from the Colon Cancer Family Registry
    Jenny N Poynter
    Department of Preventive Medicine, University of Southern California, 1441 Eastlake Avenue, NOR4411A, Los Angeles, CA 90089 9175, USA
    Cancer Res 67:11128-32. 2007
  7. pmc Genetic variability in the MTHFR gene and colorectal cancer risk using the colorectal cancer family registry
    A Joan Levine
    USC Keck School of Medicine, Department of Preventive Medicine, Genetic Epidemiology, NRT 1450 Biggy Street, Room 1509A, Los Angeles, CA 90033, USA
    Cancer Epidemiol Biomarkers Prev 19:89-100. 2010

Scientific Experts

  • A Joan Levine
  • D C Thomas
  • Jenny N Poynter
  • Jane C Figueiredo
  • David V Conti
  • Loic Le Marchand
  • John Hopper
  • David Duggan
  • Polly Newcomb
  • Peter T Campbell
  • Maria Elena Martinez
  • Won H Lee
  • Juan Pablo Lewinger
  • Robert W Haile
  • Paul J Limburg
  • Cornelia M Ulrich
  • John Potter
  • John A Baron
  • Mark A Jenkins

Detail Information

Publications7

  1. pmc Genes involved with folate uptake and distribution and their association with colorectal cancer risk
    Jane C Figueiredo
    Department of Preventive Medicine, Keck School of Medicine, University of Southern California, 1450 Biggy Street Room 1509J, Los Angeles, CA 90033, USA
    Cancer Causes Control 21:597-608. 2010
    ..In conclusion, we found no significant evidence that genetic variants in FOLR1, GGH, FPGS and SLC19A1 are associated with the risk of colorectal cancer...
  2. pmc 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
    Jenny N Poynter
    Department of Preventive Medicine, University of Southern California, Los Angeles, California, USA
    Cancer Epidemiol Biomarkers Prev 19:525-36. 2010
    ..Overall, our results do not provide evidence for a role of common genetic variants in VDR or GC in susceptibility to CRC...
  3. pmc A candidate gene study of folate-associated one carbon metabolism genes and colorectal cancer risk
    A Joan Levine
    USC Keck School of Medicine, Department of Preventive Medicine, Genetic Epidemiology, NRT 1450 Biggy Street Room 1509A, Los Angeles, CA 90033, USA
    Cancer Epidemiol Biomarkers Prev 19:1812-21. 2010
    ..Folate-associated one-carbon metabolism (FOCM) may play an important role in colorectal carcinogenesis. Variation in FOCM genes may explain some of the underlying risk of colorectal cancer...
  4. pmc Use of pathway information in molecular epidemiology
    Duncan C Thomas
    Department of Preventive Medicine, University of Southern California, 1540 Alcazar St, CHP 220, Los Angeles, CA 90089 9011, USA
    Hum Genomics 4:21-42. 2009
    ..The review concludes with some thoughts about potential uses of pathways in genome-wide association studies...
  5. pmc Cancer risks for the relatives of colorectal cancer cases with a methylated MLH1 promoter region: data from the Colorectal Cancer Family Registry
    A Joan Levine
    Department of Preventive Medicine, Genetic Epidemiology, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA
    Cancer Prev Res (Phila) 5:328-35. 2012
    ....
  6. ncbi Variants on 9p24 and 8q24 are associated with risk of colorectal cancer: results from the Colon Cancer Family Registry
    Jenny N Poynter
    Department of Preventive Medicine, University of Southern California, 1441 Eastlake Avenue, NOR4411A, Los Angeles, CA 90089 9175, USA
    Cancer Res 67:11128-32. 2007
    ..These data suggest that common variants may play important roles in the risk of CRC...
  7. pmc Genetic variability in the MTHFR gene and colorectal cancer risk using the colorectal cancer family registry
    A Joan Levine
    USC Keck School of Medicine, Department of Preventive Medicine, Genetic Epidemiology, NRT 1450 Biggy Street, Room 1509A, Los Angeles, CA 90033, USA
    Cancer Epidemiol Biomarkers Prev 19:89-100. 2010
    ..The MTHFR C677T TT genotype is associated with a 15% to 18% reduction in colorectal cancer risk, but it is not clear if other variants of the gene are associated with colorectal cancer risk...