Association of Methylenetetrahydrafolate Reductase Gene Polymorphism (MTHFR) in Patients with Gallbladder Cancer

J Gastrointest Cancer. 2016 Mar;47(1):55-60. doi: 10.1007/s12029-015-9794-0.


Purpose: 5,10-Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in folate metabolism and plays a major role in DNA methylation. There are two popular MTHFR polymorphisms known as C677T and A1298C which are found to be involved in folate metabolism and lowering the enzyme activity, thus may be linked with cancer development. This study aims to look at the association of these polymorphisms in gallbladder cancer.

Methods: Thirty patients each with gallbladder cancer, cholelithiasis, and normal gallbladder were genotyped for the above-given polymorphisms by PCR-restriction fragment length polymorphism (RFLP) method.

Results: C677T MTHFR polymorphism was not associated (χ(2) = 2.44, p = 0.85) with an increased likelihood of having gallbladder cancer. A1298C was significantly associated (χ(2) = 28.87, p < 0.001) with risk of developing gallbladder cancer. A1298C was significantly correlated with grade (r = 0.337, p < 0.001) and histopathology (r = 0.446, p < 0.001).

Conclusion: This study proposed that MTHFR A1298C polymorphism may be associated with risk of developing gallbladder cancer, and there is no association between C677T polymorphism and gallbladder cancer.

Keywords: 5,10-Methylenetetrahydrofolate reductase (MTHFR); A1298C; C677T; Gallbladder cancer; Restriction fragment length polymorphism (RFLP).

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Adult
  • Biomarkers, Tumor / genetics*
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Case-Control Studies
  • Female
  • Follow-Up Studies
  • Gallbladder Neoplasms / genetics*
  • Gallbladder Neoplasms / pathology
  • Humans
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Middle Aged
  • Neoplasm Staging
  • Prognosis


  • Biomarkers, Tumor
  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)