Polymorphisms in DNA Repair and Xenobiotic Biotransformation Enzyme Genes and Lung Cancer Risk in Coal Mine Workers.

Abstract

Background: Currently coal mining employs over 7 million miners globally. This occupational setting is associated with exposure to dust particles, heavy metals, polycyclic aromatic hydrocarbons and radioactive radon, significantly increasing the risk of lung cancer (LC). The susceptibility for LC is modified by genetic variations in xenobiotic detoxification and DNA repair capacity. The aim of this study was to investigate the association between GSTM1 (deletion), APEX1 (rs1130409), XPD (rs13181) and NBS1 (rs1805794) gene polymorphisms and LC risk in patients who worked in coal mines. Methods: The study included 639 residents of the coal region of Western Siberia (Kemerovo region, Russia): 395 underground miners and 244 healthy men who do not work in industrial enterprises. Genotyping was performed using real-time and allele-specific PCR. Results: The results show that polymorphisms of APEX1 (recessive model: ORadj = 1.87; CI 95%: 1.01–3.48) and XPD (log additive model: ORadj = 2.25; CI 95%: 1.59–3.19) genes were associated with increased LC risk. GSTM1 large deletion l was linked with decreased risk of LC formation (ORadj = 0.59, CI 95%: 0.36–0.98). The multifactor dimensionality reduction method for 3-loci model of gene–gene interactions showed that the GSTM1 (large deletion)—APEX1 (rs1130409)—XPD (rs13181) model was related with a risk of LC development. Conclusions: The results of this study highlight an association between gene polymorphism combinations and LC risks in coal mine workers.