Original paper

Cancer Causes & Control

, Volume 25, Issue 9, pp 1119-1129

First online:

Dietary B vitamin and methionine intake and MTHFR C677T genotype on risk of colorectal tumors in Lynch syndrome: the GEOLynch cohort study

  • Audrey Y. JungAffiliated withDepartment for Health Evidence, Radboud University Medical Center
  • , Fränzel J. B. van DuijnhovenAffiliated withDivision of Human Nutrition, Wageningen UniversityNational Institute for Public Health and the Environment (RIVM)
  • , Fokko M. NagengastAffiliated withDepartment of Gastroenterology, Radboud University Medical Center
  • , Akke BotmaAffiliated withDivision of Human Nutrition, Wageningen University
  • , Renate C. Heine-BröringAffiliated withDivision of Human Nutrition, Wageningen University
  • , Jan H. KleibeukerAffiliated withDepartment of Gastroenterology and Hepatology, University Medical Center Groningen
  • , Hans F. A. VasenAffiliated withNetherlands Foundation for the Detection of Hereditary Tumors
  • , Jan L. HarryvanAffiliated withDivision of Human Nutrition, Wageningen University
  • , Renate M. WinkelsAffiliated withDivision of Human Nutrition, Wageningen University
    • , Ellen KampmanAffiliated withDepartment for Health Evidence, Radboud University Medical CenterDivision of Human Nutrition, Wageningen UniversityDepartment for Health Sciences, VU University Medical Center Email author 

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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.


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.


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.


There was no suggestion that intake of any dietary B vitamin or methionine was associated with CRT development among those with LS.


B vitamins Colorectal cancer Colorectal adenoma Lynch syndrome Folate Diet