Polymorphisms in the methylenetetrahydrofolate reductase gene (MTHFR) are associated with susceptibility to adult acute myeloid leukemia in a Chinese population

Cancer Epidemiol. 2015 Jun;39(3):328-33. doi: 10.1016/j.canep.2015.02.012. Epub 2015 Apr 14.


Background: Methylenetetrahydrofolate reductase (MTHFR) is an essential enzyme in the metabolism of folate. Since acute myeloid leukemia (AML) is characterized by rapidly proliferating tissues that have a high requirement for DNA synthesis, it is possible that the presence of MTHFR polymorphisms could be linked to the multifactorial process of AML development.

Methods: We evaluated the role of MTHFR C677T and A1298C polymorphisms in a case-control study comprising 98 AML patients and 2016 healthy controls in a Southern Chinese population. We further conducted a sub-study restricted to individuals who neither smoked nor drank alcohol (70 AML patients and 160 healthy controls). MTHFR polymorphisms in the patient and control groups were evaluated by SNaP shot genotype techniques and Illumina BeadChip, respectively. Logistic regression was used to assess the adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs).

Results: The MTHFR 1298AC genotype and the 677CC/1298AC haplotype were significantly associated with a decreased risk of AML compared with the AA genotype and 677CC/1298AA haplotype (OR=0.60, 95% CI: 0.38-0.95, P=0.03; OR=0.49, 95% CI: 0.27-0.90, P=0.02, respectively). In addition, the 677TT genotype was significantly associated with an increased risk of AML compared with the AA genotype only in non-smokers and non-drinkers (OR=4.78; 95% CI=1.38-16.61, P=0.01).

Conclusions: The results might suggest that MTHFR polymorphisms are significantly associated with AML risk. In addition, the role of MTHFR genetic susceptibility could be greater among non-smokers and non-drinkers.

Keywords: AML; MTHFR; Polymorphism; Risk.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Asian Continental Ancestry Group / genetics*
  • Case-Control Studies
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Humans
  • Leukemia, Myeloid, Acute / genetics*
  • Logistic Models
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Odds Ratio
  • Oligonucleotide Array Sequence Analysis
  • Polymorphism, Single Nucleotide


  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)