Associations of polycyclic aromatic hydrocarbons exposure and its interaction with XRCC1 genetic polymorphism with lung cancer: A case-control study

Humans are extensively exposed to polycyclic aromatic hydrocarbons (PAHs) daily via multiple pathways. Epidemiological studies have demonstrated that occupational exposure to PAHs increases the risk of lung cancer, but related studies in the general population are limited. Hence, we conducted a case-control study among the Chinese general population to investigate the associations between PAHs exposure and lung cancer risk and analyze the modifications of genetic polymorphisms in DNA repair genes. In this study, we enrolled 122 lung cancer cases and 244 healthy controls in Wuhan, China. Urinary PAHs metabolites were determined by gas chromatography-mass spectrometry, and rs25487 in X-ray repair cross-complementation 1 (XRCC1) gene was genotyped by the Agena Bioscience MassARRAY System. Then, multivariable logistic regression models were performed to estimate the potential associations. We found that urinary hydroxynaphthalene (OH-Nap), hydmxyphenanthrene (OH-Phe) and the sum of hydroxy PAHs (Sigma OH-PAHs) levels were significantly higher in lung cancer cases than those in controls. After adjusting for gender, age, BMI, smoking status, smoking packyears, drinking status and family history, urinary Sigma OH-Nap and Sigma OH-Phe levels were positively associated with lung cancer risk, with dose-response relationships. Compared with those in the lowest tertiles, individuals in the highest tertiles of Sigma OH-Nap and Sigma OH-Phe had a 2.13-fold (95% CI: 1.10, 4.09) and 2.45-fold (95% CI: 1.23, 4.87) increased risk of lung cancer, respectively. Effects of gender, age, smoking status and smoking pack-years on the associations of PAHs exposure with lung cancer risk were shown in the subgroup analysis. Furthermore, associations of urinary Sigma OH-Nap and Sigma OH-PAHs levels with lung cancer risk were modified by XRCC1 rs25487 (P-interaction <= 25), and were more pronounced in wild-types of rs25487. These findings suggest that environmental exposure to naphthalene and phenanthrene is associated with increased lung cancer risk, and polymorphism of XRCC1 rs25487 might modify the naphthalene exposure-related lung cancer effect.

Automated summary

This study found that urinary metabolites of naphthalene and phenanthrene were positively associated with lung cancer risk, and the genetic polymorphism of X-ray repair cross-complementation 1 gene may modify this association.