title: Gene-diet-interactions in folate-mediated one-carbon metabolism modify colon cancer risk.
abstract: METHODS
  The importance of folate-mediated one-carbon metabolism (FOCM) in colorectal carcinogenesis is emphasized by observations that high dietary folate intake is associated with decreased risk of colon cancer (CC) and its precursors. Additionally, polymorphisms in FOCM-related genes have been repeatedly associated with risk, supporting a causal relationship between folate and colorectal carcinogenesis.
  
  
  RESULTS
  We investigated ten candidate polymorphisms with defined or probable functional impact in eight FOCM-related genes (SHMT1, DHFR, DNMT1, MTHFD1, MTHFR, MTRR, TCN2, and TDG) in 1609 CC cases and 1974 controls for association with CC risk and for interaction with dietary factors. No polymorphism was statistically significantly associated with overall risk of CC. However, statistically significant interactions modifying CC risk were observed for DNMT1 I311V with dietary folate, methionine, vitamin B2 , and vitamin B12 intake and for MTRR I22M with dietary folate, a predefined one-carbon dietary pattern, and vitamin B6 intake. We observed statistically significant gene-diet interactions with five additional polymorphisms.
  
  
  CONCLUSIONS
  Our results provide evidence that FOCM-related dietary intakes modify the association between CC risk and FOCM allelic variants. These findings add to observations showing that folate-related gene-nutrient interactions play an important role in modifying the risk of CC.
authors.affiliation: Department of Epidemiology, University of Washington, Seattle, WA, USA.
authors.forename: Amy Y
authors.initials: AY
authors.lastname: Liu
authors.forename: Dominique
authors.initials: D
authors.lastname: Scherer
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Poole
authors.forename: John D
authors.initials: JD
authors.lastname: Potter
authors.forename: Karen
authors.initials: K
authors.lastname: Curtin
authors.forename: Karen
authors.initials: K
authors.lastname: Makar
authors.forename: Martha L
authors.initials: ML
authors.lastname: Slattery
authors.forename: Bette J
authors.initials: BJ
authors.lastname: Caan
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: Ulrich
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D004032:Diet; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage* / Q000097:blood; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D012696:Glycine Hydroxymethyltransferase / Q000235:genetics; D006801:Humans; D008297:Male; D008715:Methionine / Q000008:administration & dosage; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP) / Q000235:genetics; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens; D011110:Polymorphism, Genetic; D012256:Riboflavin / Q000008:administration & dosage; D012307:Risk Factors; D014805:Vitamin B 12 / Q000008:administration & dosage; D025101:Vitamin B 6 / Q000008:administration & dosage
chemical_list: D015778:Minor Histocompatibility Antigens; D025101:Vitamin B 6; D005492:Folic Acid; D008715:Methionine; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); C539735:MTHFD1 protein, human; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP); D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human; D012696:Glycine Hydroxymethyltransferase; C520541:SHMT protein, human; D014805:Vitamin B 12; D012256:Riboflavin