Total CAs and chromosome-type aberrations (CSAs) were significantly increased by higher age alone, whereas chromatid-type aberrations (CTAs) were elevated by the GSTT1-null genotype and MTHFR codon 222 variant allele and chromatid gaps (CTGs) by EPHX1 high activity genotype and occupational exposure.
Five years later, 51 tank car workers and 40 age-matched referents (all nonsmoking men) were studied for CAs and genetic polymorphisms of xenobiotic metabolism (EPHX1, GSTM1, GSTP1, GSTT1, NAT1, NAT2), DNA repair (ERCC2, ERCC5, XPA, XPC, XRCC1, XRCC3), and folate metabolism (MTHFR, MTR).
Individuals with low activity EPHX1 genotype exhibited significantly higher chromosomal aberrations (2.3+/-1.6%) in comparison with those bearing medium (1.7+/-1.2%) and high activity genotype (1.5+/-1.2%; F=4.7, P=0.010).
The aim of the study was to elucidate whether the frequency of BLM-induced CAs is correlated with polymorphisms of selected genes involved in different mechanisms of DNA repair such as: XRCC1 [base excision repair]; XPA, XPC, XPG, XPD, XPF, ERCC1 [nucleotide excision repair], NBS1, RAD51, XRCC2, XRCC3, RAD51, and BRCA1 [homologous recombination], as well as in genes encoding xenobiotic metabolizing enzymes, such as CYP1A, CYP2E1, NAT2, GSTT1, and EPHX (mEH).
The GSTT1 null genotype was associated with increased MNBN frequencies in the exposed workers (P<0.05) and the fast activity EPHX genotype with a moderate decrease in both MNBN and CAs in the controls.
In evaluations conducted with the markers of individual susceptibility, workers with low-EPHX1-activity genotypes exhibited a significantly higher CA frequency as compared to those with medium and high-EPHX1-activity genotypes (P = 0.050).
In conclusion, the CA data provides evidence to support that susceptibility mEH alleles are significantly involved with the development of lung cancer from cigarette smoking.