Our results showed that the variant allele of mEPHX exon 4 increased the overall lung cancer risk by 56% (odds ratio [OR]=1.56, 95% confidence interval [CI]=0.99-2.46).
Among genetic polymorphisms reviewed here, myeloperoxidase gene (a G to A mutation) and microsomal epoxide hydrolase exon 4 polymorphism (substitution of Arg for His) were significantly associated with lung cancer risk.
Our results agree with these observations in vitro and suggest that a genetically determined combination of a high-activity mEH and a low-activity GSTpi may increase lung cancer risk among smokers.
These findings suggest that the presence of the exon 4 and exon 3 polymorphisms of mEPHX may be associated with an increased risk of lung cancer particularly among younger Mexican-Americans in this study.
A combination of susceptible CYP1A1 and HYL1 genotypes was found to be highly associated with lung cancer, especially with SCC (OR 6.76; 95% CI 2.29-19.10).
Although the three published results for Caucasians are somewhat variable, the association among African-Americans in these data provides some support for the hypothesis that genetically reduced microsomal epoxide hydrolase activity may be protective against lung cancer.
Activity of microsomal epoxide hydrolase (HYL1) has also been associated with lung cancer, and 2 variant alleles causing amino acid substitutions have been described.
The effect of mEH activity on lung cancer risk was not significantly modified by smoking exposure, CYP1A1 genotype, or GSTM1 genotype. mEH may thus be an important genetic determinant of smoking-induced lung cancer.