Epistatic interactions in DNA repair genes as biomarkers of susceptibility for DNA damage in pesticide-exposed agricultural workers of Punjab, North-West India.

Some occupational exposures to pesticides have been associated with genotoxicity which arises from DNA single-strand breaks (SSBs), repair of DNA double-strand breaks (DSBs), DNA adduct formation, or DNA-DNA and DNA-protein cross-links. Polymorphisms in genes encoding enzymes of DNA repair pathways may modulate the individual's susceptibility to pesticide-induced genotoxicity. A total of 450 subjects were included in this study, which comprises 225 agricultural workers exposed to complex mixtures of pesticides and 225 non-exposed controls from Punjab, North-West India. Susceptibility of OGG1 Ser326Cys (C1245G), XRCC1 Arg194Trp (C26304T), XRCC1 Arg399Gln (G28152A), XPC Lys939Gln (A2920C), XPC Ala499Val (C21151T), XPD Asp312Asn (G23591A), XPD Lys715Gln (A35931C), XPF Arg415Gln (G1244A), XPG Asp1104His (G3507C), ERCC1 3'-UTR (C8092A) and ERCC1 Asn118Asn (C354T) gene polymorphisms with pesticide-induced DNA damage was determined by Kruskal-Wallis test. The association of epistatic gene interactions with DNA damage was studied by ANOVA. The results indicated significant interactions of variant OGG1 326Ser/Cys genotype with XRCC1 194Arg/Trp and XRCC1 399Arg/Gln genotypes in increased susceptibility to DNA damage. XPC 939Gln/Gln genotype significantly interacts with XPC 499Ala/Val, XPD 312Asp/Asp and XPD 715Gln/Gln variant genotypes to increase DNA damage susceptibility. Among exposed XPF 415Gln/Gln individuals, DNA damage was significantly higher in those individuals who had variant XPG Asp/His and ERCC1 8092CA genotypes. We observed some statistically significant epistatic gene interactions in DNA repair pathways in modulating DNA damage, which may be used as biomarkers of susceptibility in pesticide-exposed agricultural workers of Punjab, North-West India.