MTHFR (C677T and A1298C) polymorphisms and risk of sporadic distal colorectal adenoma in the UK Flexible Sigmoidoscopy Screening Trial (United Kingdom)

Cancer Causes Control. 2006 Aug;17(6):793-801. doi: 10.1007/s10552-006-0016-8.


Objective: The purpose of this study was to further evaluate the role of low activity MTHFR variants as well as to explore interactive effects between alcoholic drink consumption and MTHFR variants and risk of distal colorectal adenomatous polyps.

Methods: We examined the relationship between MTHFR C677T and A1298C gene polymorphisms and risk of distal adenomas in one of the largest case control studies of 946 polyp-free controls and 894 cases, all participants of the UK Flexible Sigmoidoscopy Screening Trial (UKFSS).

Results: Investigation of the effect of the MTHFR C677T polymorphism in this large UKFSS study revealed no overall association on adenoma risk (P>0.05). However the MTHFR 1298C allele was linked, for the first time, to high risk adenomas, although in males only (odds ratio (OR) for A/C+C/C compared with A/A 1.55; 95% confidence interval (CI), 1.08-2.22; P=0.018).

Conclusions: In this, the largest study of these polymorphisms in relation to colorectal adenoma, there was no evidence for an interaction with alcohol in combination with the variant forms of MTHFR (P>0.05).

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • 5,10-Methylenetetrahydrofolate Reductase (FADH2) / genetics*
  • Adenoma / enzymology
  • Adenoma / genetics*
  • Adenomatous Polyps / genetics*
  • Aged
  • Alcohol Drinking
  • Case-Control Studies
  • Colorectal Neoplasms / enzymology
  • Colorectal Neoplasms / genetics*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Mass Screening
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*
  • Risk Factors
  • Sigmoidoscopy / methods


  • 5,10-Methylenetetrahydrofolate Reductase (FADH2)