• Media type: E-Article
  • Title: Association of dietary and supplemental folate intake and polymorphisms in three FOCM pathway genes with colorectal cancer in a population‐based case‐control study
  • Contributor: Ashmore, Joseph H.; Lesko, Samuel M.; Muscat, Joshua E.; Gallagher, Carla J.; Berg, Arthur S.; Miller, Paige E.; Hartman, Terryl J.; Lazarus, Philip
  • imprint: Wiley, 2013
  • Published in: Genes, Chromosomes and Cancer
  • Language: English
  • DOI: 10.1002/gcc.22089
  • ISSN: 1045-2257; 1098-2264
  • Origination:
  • Footnote:
  • Description: <jats:p>Previous research has shown that greater intakes of dietary folate are associated with reduced risk for colorectal cancer (CRC) and that single nucleotide polymorphisms (SNPs) in genes involved in folate‐mediated one‐carbon metabolism (FOCM) also may be involved in altering CRC risk. The objective of this study was to evaluate the role of folate intake (and intakes of related dietary components such as methionine), 35 SNPs in three FOCM pathway genes (<jats:italic>MTHFD1</jats:italic>, <jats:italic>MTHFR</jats:italic>, and <jats:italic>TYMS</jats:italic>), and their interactions on CRC risk in a population‐based case‐control study in Pennsylvania (686 cases, 740 controls). Diet and supplement use was assessed for the year before diagnosis or interview for cases and controls, respectively, with a modified Diet History Questionnaire from the National Cancer Institute. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using unconditional logistic regression. Using a dominant model for the variant allele, several SNPs were significantly associated with CRC including <jats:italic>MTHFD1</jats:italic> rs8003379 (OR = 1.65; 95% CI = 1.00−2.73) and rs17824591 (OR = 1.98; 95% CI = 1.14−3.41) and the <jats:italic>TYMS</jats:italic> rs2853533 SNP (OR = 1.38; 95% CI = 1.05−1.80). Using a nondominant model, the AA genotype for <jats:italic>MTHFR</jats:italic> rs1476413 exhibited a marginally significant (OR = 1.56; 95% CI = 1.00−2.44) association with CRC. Two <jats:italic>TYMS</jats:italic> SNPs (rs16948305 and rs495139) exhibited significant (<jats:italic>P</jats:italic> = 0.024 and <jats:italic>P</jats:italic> = 0.040, respectively) gene‐diet interactions with folate intake. One <jats:italic>MTHFD1</jats:italic> (<jats:italic>P</jats:italic> = 0.019) and one <jats:italic>MTHFR</jats:italic> (<jats:italic>P</jats:italic> = 0.042) SNP exhibited gene‐diet interactions with methionine intake. These findings suggest that allelic variants in genes involved in FOCM interact with dietary factors including folate and methionine to modify risk for CRC. © 2013 Wiley Periodicals, Inc.</jats:p>