Polymorphism of Inflammatory genes and Arsenic Methylation Capacity are Associated with Urothelial Carcinoma

摘要

Background: Chronic exposure to arsenic can generate reactive oxidative species, which can induce certain proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-a), interleukin-6 (IL-6) and interleukin-8 (IL-8). TNF-a, IL-6 and IL-8 have been shown to be involved in the development and progression of various cancers, including bladder cancer. Aims: This study aimed to investigate the joint effect of the polymorphismof TNF-a-308 G/A,IL-6-174G/C, IL-8-251T/A and urinary arsenic profiles on urothelial carcinoma (UC) risk. Methods: This study evaluated 300 pathologically-confirmed cases of UC and 594 cancer-free controls.Urinary arsenic species were detected using high-performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. The polymorphismof TNF-a-308 G/A, IL-6-174G/C and IL-8-251 T/Awere determined using polymerase chain reaction-restriction fragment length polymorphism. The joint effects on UC risk were estimated by odds ratios and 95% confidence intervals using unconditional logistic regression. Results: We found that theTNF-a-308 A/A and IL-8-251 T/T polymorphisms were significantly associated with UC. Moreover, the significant dose-response of the joint effect of TNF-a-308 A/A or IL-8-251 T/T genotypes and arsenic methylation indices were seen to affect UC risk. Conclusions:Our data provided evidence that subjects with high urinary total arsenic levels may experience an increased risk of UC if either IL-8-251 T/T or TNF-α A/A genotypes are present.