Association of polymorphisms in one-carbon metabolizing genes and lung cancer risk: a case-control study in Chinese population

Lung Cancer. 2008 Jul;61(1):21-9. doi: 10.1016/j.lungcan.2007.12.001. Epub 2008 Jan 24.

Abstract

One-carbon metabolism facilitates the cross-talk between genetic and epigenetic processes, making it a good candidate for studying the risk of lung cancer. To investigate the role of common variants of one-carbon metabolizing genes on lung cancer risk, total 25 single nucleotide polymorphisms (SNPs) in 7 genes were genotyped among 500 incident lung cancer patients and 517 cancer-free controls. An increased risk was suggested for the variant allele carriers of MTHFR rs17037396 [odds ratio (OR)=1.39, 95% confidence interval (CI): 1.00-1.94] and rs3753584 (OR=1.46, 95% CI: 1.03-2.08), compared with subjects with wild homozygote, respectively, and the risk was more pronounced among older individuals (>60 years). In contrast, a decreased risk was observed for TYMS rs2853742 variant allele carriers (OR=0.44, 95% CI: 0.19-0.99) and MTHFD rs2236225 variant allele carriers (OR=0.76, 95% CI: 0.59-0.99). Haplotype analysis revealed that MTHFR "ACCACC" haplotype may contribute to the risk of lung cancer (OR=1.49, 95% CI: 1.03-2.14, local test p value 0.032). A data mining method, multifactor dimensionality reduction (MDR), predicted a four-factor interaction model (rs1801133, rs4659731, rs2273029 and rs699517) with the lowest average prediction error (45.08%, p<0.001). These findings suggest that genetic variants in one-carbon metabolizing genes might modulate the risk of lung cancer. Validation of these findings in larger studies is needed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian Continental Ancestry Group
  • Case-Control Studies
  • Female
  • Genetic Predisposition to Disease*
  • Humans
  • Lung Neoplasms / genetics*
  • Male
  • Middle Aged
  • One-Carbon Group Transferases / genetics*
  • Polymorphism, Single Nucleotide*
  • Risk Factors

Substances

  • One-Carbon Group Transferases