title: Dietary B vitamin and methionine intake and MTHFR C677T genotype on risk of colorectal tumors in Lynch syndrome: the GEOLynch cohort study.
abstract: OBJECTIVE
  Dietary intake of B vitamins and methionine, essential components of DNA synthesis and methylation pathways, may influence colorectal tumor (CRT) development. The impact of B vitamins on colorectal carcinogenesis in individuals with Lynch syndrome (LS) is unknown but is important given their high lifetime risk of developing neoplasms. The role of MTHFR C677T genotype in modifying these relationships in LS individuals is also unclear. We investigated associations between dietary intakes of folate, vitamins B2, B6, B12, and methionine and CRT development in a prospective cohort study of 470 mismatch repair gene mutation carriers.
  
  
  METHODS
  Dietary intakes were assessed by food frequency questionnaire. Cox regression models with robust sandwich covariance estimation, adjusted for age, sex, physical activity, number of colonoscopies during person-time, NSAID use, and mutual vitamins were used to calculate hazard ratios (HRs) and 95 % confidence intervals (95 % CIs). Analyses were also stratified by MTHFR C677T genotype.
  
  
  RESULTS
  During a median person-time of 28.0 months, 131 persons developed a CRT. Fifty-one of these persons developed an incident colorectal adenoma, while there were four persons who developed an incident colorectal carcinoma. Compared to the lowest tertile of intake, adjusted HRs (95 % CIs) for CRT development in the highest tertile were 1.06 (0.59-1.91) for folate, 0.77 (0.39-1.51) for vitamin B2, 0.98 (0.59-1.62) for vitamin B6, 1.24 (0.77-2.00) for vitamin B12, and 1.36 (0.83-2.20) for methionine. Low vitamin B2 and low methionine intake were statistically significantly associated with an increased risk of CRT in MTHFR 677TT individuals compared to a combined reference of persons with low intake and CC genotype.
  
  
  CONCLUSIONS
  There was no suggestion that intake of any dietary B vitamin or methionine was associated with CRT development among those with LS.
authors.affiliation: Department for Health Evidence, Radboud University Medical Center, Nijmegen, Netherlands.
authors.forename: Audrey Y
authors.initials: AY
authors.lastname: Jung
authors.forename: Fränzel J B
authors.initials: FJ
authors.lastname: van Duijnhoven
authors.forename: Fokko M
authors.initials: FM
authors.lastname: Nagengast
authors.forename: Akke
authors.initials: A
authors.lastname: Botma
authors.forename: Renate C
authors.initials: RC
authors.lastname: Heine-Bröring
authors.forename: Jan H
authors.initials: JH
authors.lastname: Kleibeuker
authors.forename: Hans F A
authors.initials: HF
authors.lastname: Vasen
authors.forename: Jan L
authors.initials: JL
authors.lastname: Harryvan
authors.forename: Renate M
authors.initials: RM
authors.lastname: Winkels
authors.forename: Ellen
authors.initials: E
authors.lastname: Kampman
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D015331:Cohort Studies; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000097:blood / Q000235:genetics*; D004032:Diet; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008715:Methionine / Q000008:administration & dosage*; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D009426:Netherlands; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012256:Riboflavin / Q000008:administration & dosage; D012307:Risk Factors; D011795:Surveys and Questionnaires; D014803:Vitamin B Complex / Q000008:administration & dosage*; D044465:White People / Q000235:genetics
chemical_list: D014803:Vitamin B Complex; D008715:Methionine; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D012256:Riboflavin