[Role of gene polymorphisms of phase II of xenobiotic biotransformation from glutathione-S-transferase and N-acetyltransferase families in susceptibility to lung cancer among Mayak workers].

ABSTRACT

An association between polymorphous (allelic) gene variants of phase II of enzymatic xenobiotic biotransformation (EXB) of multigene families of glutathione-S-transferase (GSTs) GSTM1*0, GSTT1*0, GSTP1*B Ile105Val, and N-acetyltransferase (NAT) NAT2*6 590G>A, NAT2*5 481C>T, as well as lung cancer in Mayak workers exposed occupationally to prolonged external γ-rays and internal α-radiation from incorporated 239Pu was studied. Analysis of the population frequency of genotypes and alleles of the studied genes in the cohort of Mayak workers revealed their compliance with the Hardy-Weinberg principle and with the corresponding frequency in the European population. The study was based on the case-control method. A case-group consisted of 49 Mayal workers with a verified diagnosis of lung cancer. The mean total absorbed dose from external γ-rays at the moment of diagnostics was 1.03 Gy; the mean total absorbed dose from internal α-radiation from incorporated 239Pu to lung was 0.35 Gy. Control consisted of 172 Mayak workers matched by the year of birth, gender, and age at the moment of employment at one of the main facilities with no lung cancer registered within the study period. No increase in the relative risk of lung cancer (odds ratio, OR) was revealed among the individuals with deletion variants of genes GSTM1*0 and GSTT1*0 (pp genotype, complete absence of gene products) as compared to the individuals with ww or wp genotype, which was determined in total for these genes (normal or partly decreased gene activity). An increase in OR of lung cancer in 1.849 times (p = 0.239) and in 2.439 times (p = 0.075) was found in the carriers with a complete absence of the product of genes GSTP1*B and NAT2*6 590G>A, correspondingly (pp genotype). A statistically significant decrease in OR of lung cancer was found in the wp genotype carriers of gene GSTP1*B (OR = 0.50, p = 0.041). Three variants of paired combinations of gene alleles were established in the carriers with a statistically significant increase in OR of lung cancer (ww GSTP1*B + pp GSTM1*0; ww GSTP1*B + pp NAT2*6 590G>A; pp GSTP1*B + pp NAT2*5 481C>T), and one combination in the carriers with a statistically significant decrease in OR of lung cancer (wp GSTP1*B and ww +wp GSTT1*0).