Methylenetetrahydrofolate reductase polymorphisms/haplotypes and risk of gastric cancer: A case-control analysis in China

Hongbing Shen, Ana S. Newmann, Zhibin Hu, Zhengdong Zhang, Yaochu Xu, Liwei Wang, Xu Hu, Jiangtao Guo, Xinru Wang, Qingyi Wei

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

Studies have suggested that low dietary folate intake is associated with an increased risk of gastric cancer. Methylenetetrahydrofolate reductase (MTHFR) is involved in folate metabolism and influences DNA methylation and nucleotide synthesis. MTHFR is highly polymorphic and the variant genotypes result in decreased MTHFR enzyme activity and lower plasma folate level. We hypothesized that three MTHFR common variants (i.e. C677T, A1298C and G1793A) and their haplotypes are associated with the risk of gastric cancer. To test this hypothesis, we genotyped these polymorphisms in a population-based case-control study of 320 incident gastric adenocarcinoma cases and 313 cancer-free controls in a Chinese population. Consistent with our previous observations, the 677TT genotype was associated with a significantly increased risk for gastric cancer (adjusted OR =1.79, 95% CI =1.02-3.15) compared with the 677CC genotype; the association was more evident for gastric cardia adenocarcinoma (adjusted OR =2.60, 95% CI =1.30-5.21). When we used the haplotype analyses and assumed MTHFR 677T, 1298C and 1793A as risk alleles, individuals with 6 variant alleles had a significantly (4.64-fold) increased risk for gastric cardia adenocarcinoma (OR =4.64, 95% CI =1.34-16.01) compared with those having 0-2 variants. These findings suggest that the MTHFR common variants and their haplotypes may play a role in the etiology of gastric cancer, particularly gastric cardia adenocarcinoma. Future studies using large sample sizes and incorporating detailed data on dietary folate intake and related serological measurements are warranted to confirm our findings.

Original languageEnglish (US)
Pages (from-to)355-360
Number of pages6
JournalOncology reports
Volume13
Issue number2
StatePublished - Feb 2005

Keywords

  • Gastric cancer
  • Genetic polymorphism
  • Methylenetetrahydrofolate reductase
  • Molecular epidemiology

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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