Genes involved with folate uptake and distribution and their association with colorectal cancer risk

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

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Folate status is an important predictor of colorectal cancer risk. Common genetic variants in genes involved in regulating cellular folate levels might also predict risk, but there are limited data on this issue. We conducted a family-based case-control association study of variants in four genes involved in folate uptake and distribution: FOLR1, FPGS, GGH and SLC19A1, using 1, 750 population-based and 245 clinic-based cases of pathologically confirmed colorectal cancer and their unaffected relatives participating in the Colon Cancer Family Registries. Standardized questionnaires, administered to all participants, collected information on risk factors and diet. Standard molecular techniques were used to determine microsatellite instability (MSI) status on cases. tagSNPs (n = 29) were selected based on coverage as assessed by pairwise r2. We found no evidence that tagSNPs in these genes were associated with risk of colorectal cancer. For the SLC19A1-rs1051266 (G80A, Arg27His) missense polymorphism, the A/A genotype was not associated with risk of colorectal cancer using population-based (OR = 1.00; 95% CI = 0.81-1.23) or clinic-based (OR = 0.75; 95% CI = 0.44-1.29) families compared to the G/A and G/G genotypes. We found no evidence that the association between any tagSNP and CRC risk was modified by multivitamin use, folic acid use and dietary folate intake and total folate intake. The odds ratios were similar, irrespective of MSI status, tumor subsite and family history of colorectal cancer. In conclusion, we found no significant evidence that genetic variants in FOLR1, GGH, FPGS and SLC19A1 are associated with the risk of colorectal cancer.

Original languageEnglish (US)
Pages (from-to)597-608
Number of pages12
JournalCancer Causes and Control
Volume21
Issue number4
DOIs
StatePublished - Apr 2010

Keywords

  • Case-control
  • Clinic-based
  • Colorectal cancer
  • Folate
  • Folate receptor 1 (FOLR1)
  • Folylpolyglutamate synthase (FPGS)
  • Gamma-glutamyl hydrolase (GGH) family-based
  • Polymorphisms
  • Population-based
  • Reduced folate carrier (RFC)
  • Solute carrier family 19 (SLC19A1)

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    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., Newcomb, P., Potter, J., Limburg, P. J., Hopper, J., Jenkins, M. A., Le Marchand, L., Baron, J. A., & Haile, R. W. (2010). Genes involved with folate uptake and distribution and their association with colorectal cancer risk. Cancer Causes and Control, 21(4), 597-608. https://doi.org/10.1007/s10552-009-9489-6