title: Folate and MTHFR: risk of adenoma recurrence in the Polyp Prevention Trial.
abstract: BACKGROUND
  Low dietary folate intake has been associated with colorectal cancer risk and adenoma recurrence. A C/T transition at position 677 in the gene encoding methlylenetetrahydrofolate reductase (MTHFR C677T) has been reported to interact with folate intake to modulate colorectal adenoma recurrence or cancer risk.
  
  
  METHODS
  We investigated the association between MTHFR, total folate, and the risk of colorectal adenoma recurrence in the Polyp Prevention Trial. We compared 625 individuals with any adenoma recurrence after 4 years (266 individuals with multiple (> or =2) recurrent adenomas and 101 individuals with advanced adenoma recurrence) to 978 individuals with no adenoma recurrence. Odds ratios (OR) and 95% confidence intervals (CI) for risk of adenoma recurrence were calculated using unconditional logistic regression. We also investigated effect modification of the MTHFR genotype associations by total folate intake.
  
  
  RESULTS
  In general, no statistically significant associations were found between quartile of folate intake (dietary or total) and adenoma recurrence. The MTHFR CT genotype was associated with a significantly increased risk of multiple adenoma recurrence (OR: 1.34, 95% CI: 1.00, 1.81). No significant interaction was noted for total folate and MTHFR genotype, though an increased risk of recurrence noted for the MTHFR CT genotype was statistically significant only for those individuals with below median intake of total folate.
  
  
  CONCLUSIONS
  We report that the MTHFR 677 CT genotype was associated with increased risk of adenoma recurrence (specifically multiple adenoma recurrence) 4 years after polypectomy.
authors.affiliation: Cancer Prevention Fellowship Program, Office of Preventive Oncology, Bethesda, MD, USA. murphygw@mail.nih.gov
authors.forename: Gwen
authors.initials: G
authors.lastname: Murphy
authors.forename: Leah B
authors.initials: LB
authors.lastname: Sansbury
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Cross
authors.forename: Rachael
authors.initials: R
authors.lastname: Stolzenberg-Solomon
authors.forename: Adeyinka
authors.initials: A
authors.lastname: Laiyemo
authors.forename: Paul S
authors.initials: PS
authors.lastname: Albert
authors.forename: Zhuoqiao
authors.initials: Z
authors.lastname: Wang
authors.forename: Arthur
authors.initials: A
authors.lastname: Schatzkin
authors.forename: Teresa
authors.initials: T
authors.lastname: Lehman
authors.forename: Aravind
authors.initials: A
authors.lastname: Kalidindi
authors.forename: Rama
authors.initials: R
authors.lastname: Modali
authors.forename: Elaine
authors.initials: E
authors.lastname: Lanza
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D000368:Aged; D000483:Alleles; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D005492:Folic Acid / Q000235:genetics; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D016017:Odds Ratio; D011795:Surveys and Questionnaires; D014803:Vitamin B Complex / Q000235:genetics
chemical_list: D014803:Vitamin B Complex; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2)