Association Between ERCC8 And ERCC6 Gene Polymorphisms And DNA Damage In Peripheral Blood Lymphocytes Among Coke Oven Workers

Polycyclic aromatic hydrocarbons (PAHs) are a well-established group of chemical carcinogens. PAHs were formed and released during the coke process, resulting in direct exposure of coke-oven workers to PAHs by inhalation and dermal contact in the working hours. In humans, carcinogenic PAHs in coke emission were metabolized to form ultimate carcinogens that could damage DNA to exert their mutagenic and carcinogenic effects. Transcription-coupled repair (TCR) is a sub-pathway of nucleotide excision repair (NER) able to remove DNA lesions so that genes can be transcribed correctly. We focus on the roles of ERCC6 and ERCC8 gene, which, when mutated, impair TCR. However, many researchers also found that the DNA repair capacities were greatly different among distinct individuals. The genetic background, which was well known to determine the individual specificity, affected DNA repair capacity, but the detail mechanisms how different genotypes determining various DNA repair capacity were still unclear. Now, the human genome project has been finished and the following functional genomics is more and more developing, especially the International HapMap Project, which describes the common patterns of human DNA sequence variation in Chinese population and provides a key resource for researchers to find genes that predispose to health, disease, and responses to drugs and environmental factors. So it was essential that we investigated the influences of ERCC8 and ERCC6 gene polymorphisms on DNA damages in coke oven workers to explore the genetic susceptibility of occupational populations. In this study, we recruited 379 workers exposed to COEs, 398 workers Recovered about 16 hours and 398 controls not exposed to COEs in the same steel plant in southern China. After adjustment for age, smoking index, drink, our results showed that the lymphocytes olive tail moment (OTM) of coke oven workers was significantly higher than that of controls and recovered. In the exposed group, The stratified analysis results implied that the OTM of those with CC genotype at Rs3793784 site was-0.71±0.69, which was significantly higher than that of those with CG+GG genotype(-0.95±0.70, P <0.05) in older people (≥37 years old). We also found that the OTM of those with AG+GG genotype at Rs2228527 site was -0.56±1.07, which was significantly higher than that of those with AA genotype(-0.86±0.71, P <0.05) in high expose people (1-OHP≥4.36μmol/mol.Cr).In conclusion, based on the determined ERCC6 and ERCC8 gene variations in Chinese population, we investigated the associations of the ERCC6 and ERCC8 polymorphisms with DNA damage in peripheral lymphocytes of coke oven workers. However, we also found that the sample size of association study was small, which may lead to the insufficient power, so our positive results should be identified by further studies of larger sample. Moreover, the functions of promoter SNPs such as Rs158920 underlie the further cell functional investigations including Electrophoretic Mobility Shift Assays, Chromatin Immunoprecipitation Assay.