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

Abstract

Purpose

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.

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Acknowledgments

We are grateful to all the participants of the GEOLynch cohort study. We thank Leontien Witjes (Wageningen University), Maria van Vugt (Radboud University Medical Center), Mary Velthuizen (Netherlands Foundation for the Detection for Hereditary Tumors), Alice Donselaar (Netherlands Foundation for the Detection of Hereditary Tumors), Carolien Lute (Wageningen University), and Ramazan Buyukcelik (Erasmus Medical Center) for their assistance with recruitment, data collection, DNA preparation, and genotyping. The work described in this paper was carried out with the support of the Dutch Cancer Society (KWF, Grant Number KUN-2007-3842).

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Correspondence to Ellen Kampman.

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Jung, A.Y., van Duijnhoven, F.J.B., Nagengast, F.M. et al. Dietary B vitamin and methionine intake and MTHFR C677T genotype on risk of colorectal tumors in Lynch syndrome: the GEOLynch cohort study. Cancer Causes Control 25, 1119–1129 (2014). https://doi.org/10.1007/s10552-014-0412-4

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Keywords

  • B vitamins
  • Colorectal cancer
  • Colorectal adenoma
  • Lynch syndrome
  • Folate
  • Diet