Gene-environment interactions between ERCC2, ERCC3, XRCC1 and cadmium exposure in nasal polyposis disease.

Abstract

Gene-environment interactions have long been known to play an important role in complex disease aetiology, such as nasal polyposis (NP). The present study supports the concept that DNA repair gene polymorphisms play critical roles in modifying individual susceptibility to environmental diseases. In fact, we investigated the role of polymorphisms in DNA repair genes and cadmium as risk factors for Tunisian patients with NP. To the best of our knowledge, this is the first report on the impact of combined effects of cadmium and ERCC3 7122 A>G (rs4150407), ERCC2 Lys751Gln (rs13181) and XRCC1 Arg399Gln (rs25487) genes in the susceptibility to NP disease. Significant associations between the risk of developing NP disease and ERCC2 [odds ratio (OR) = 2.0, 95% confidence interval (CI) = 1.1-3.7, p = 0.023] and ERCC3 (OR = 2.2, 95% CI = 1.2-4.1, p = 0.013) genotypes polymorphisms were observed. Blood concentrations of Cd in NP patients (2.2μg/L) were significantly higher than those of controls (0.5μg/L). A significant interaction between ERCC3 (7122 A>G) polymorphism and blood-Cd levels (for the median of blood-Cd levels: OR = 3.8, 95% CI = 1.3-10.8, p = 0.014 and for the 75th percentiles of blood-Cd levels: OR = 2.7, 95% CI = 1.1-7.2, p = 0.041) was found in association with the risk of NP disease. In addition, when we stratified ERCC2, ERCC3 and XRCC1 polymorphism genotypes by the median and 75th percentiles of blood-Cd levels, we found also significant interactions between ERCC2 (Lys751Gln) and ERCC3 (7122 A>G) genotypes polymorphism and this metal in association with NP disease. However, no interaction was found between XRCC1 (Arg399Gln) polymorphism genotypes and Cd in association with NP disease.