[Role of ancestral genotypes of the genes of xenobiotics biotransformation in susceptibility to lung cancer among Mayak workers].

An association between polymorphous (allelic) variants of genes of the 1st Phase of enzymatic xenobiotic biotransformation (EXB) in the superfamily of cytochromes P450 gene CYP1A1 * 2A (ml polymorphism), CYP1A1 * 2C (m2 polymorphism), gene CYP2E1 * 6 (C polymorphism), and between polymorphous vari- ants of gene of the 2nd EXB Phase of mircosomal epoxide hydrolase mEPOX Tyr113His (EH3 polymor- phism), and mEPOXHis139Arg (EH4 polymorphism) and lung cancer in Mayak workers with occupational prolonged exposure was studied. Analysis of population genotype frequency and alleles of genes CYP1A1 * 2A, CYP1A1 * 2C, CYP2E1 * 6, mEPOX Tyr113His, and mEPOXHis139Arg was conducted in the group of Mayak workers (289 individuals). The study has shown their compliance with the Hardy-Weinberg equilibrium, and correspondence of the genotype frequency to their frequency in European population. The study was per- formed using case-control method. Case-group consisted of 49 Mayak workers with verified diagnosis of lung cancer. Control-group consisted of 172 Mayak workers without lung cancer registered at the moment of the research. There was an increasing trend in odds ratio (OR) of lung cancer among homozygous carriers of the mutation in pp gene CYP1A1 * 2A, heterozygous carriers of the mutation in wp gene mEPOX Tyr113His and homozygous carriers ofww gene CYP2E1 * 6; also, there was a decreasing trend in OR among heterozy- gous carriers of wp gene CYP2E1 * 6. Two variants of pair allelic combinations of genes (genotypes ww CYP1A1 * 2A/genotype wp mEPOX Tyr113His, and genotype ww CYP2E1 * 6/genotype wp mEPOX Tyr113His) were revealed, which carriers had a statistically significant increase in the odds ratio of lung can- cer. With regard to these variants of genotype combinations, OR of lung cancer was 2.01 (CI 95%: 1.04-3.91) and 2.09 (CI 95%: 1.08-4.03), correspondingly.