Association between lung cancer risk and single nucleotide polymorphisms in the first intron and codon 178 of the DNA repair gene, O6-alkylguanine-DNA alkyltransferase

Int J Cancer. 2008 Feb 15;122(4):791-5. doi: 10.1002/ijc.23059.


The association between lung cancer risk and 2 polymorphisms, rs12268840 and rs2308327 (codon K178R), in the DNA repair protein, O(6)-alkylguanine-DNA alkyltransferase, which are associated with interindividual differences in activity, have been investigated in 3 hospital-based case-control studies. Genotyping was carried out on 617 subjects of whom 255 had lung cancer. In 2 of the 3 series, there was a significant inverse association between the 178R allele and case status (p < 0.05). In a meta-analysis, the odds ratio (95% CI) associated with the 178R allele relative to the 178K allele was 0.64 (0.45-0.92, p = 0.01) and 0.51 (0.24-1.11, p = 0.09) in fixed effects and random effects models, respectively. In a pooled analysis, after adjustment for sex, age, pack years and series, the OR (95% CI) for a heterozygote was 0.67 (0.45-1.01) and for a 178R homozygote was 0.10 (0.01-0.94); the trend for a decreased risk with the number of R alleles was significant (p = 0.008). This trend was particularly pronounced in heavy smokers (trend test p = 0.003), but not significant in light smokers (p = 0.73). There was no evidence of an association between rs12268840 and lung cancer risk. These results suggest that the R allele may protect against lung cancer, specifically in heavy smokers, an effect that may result from this polymorphism affecting the function of the MGMT protein and/or levels in MGMT activity.

Publication types

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

MeSH terms

  • Adenocarcinoma / enzymology
  • Adenocarcinoma / etiology
  • Aged
  • Carcinoma, Small Cell / enzymology
  • Carcinoma, Small Cell / etiology*
  • Carcinoma, Squamous Cell / enzymology
  • Carcinoma, Squamous Cell / etiology
  • Case-Control Studies
  • Codon / genetics*
  • DNA Repair / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Introns / genetics*
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / etiology*
  • Male
  • Middle Aged
  • O(6)-Methylguanine-DNA Methyltransferase / genetics*
  • Polymorphism, Single Nucleotide / genetics*
  • Risk Factors
  • Smoking / adverse effects


  • Codon
  • O(6)-Methylguanine-DNA Methyltransferase