Polymorphism of inflammatory genes and arsenic methylation capacity are associated with urothelial carcinoma

• Published in: Toxicology and applied pharmacology Vol. 272; no. 1; pp. 30 - 36
• Main Authors: Wu, Chia-Chang, Huang, Yung-Kai, Chung, Chi-Jung, Huang, Chao-Yuan, Pu, Yeong-Shiau, Shiue, Horng-Sheng, Lai, Li-An, Lin, Ying-Chin, Su, Chien-Tien, Hsueh, Yu-Mei
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.10.2013; Elsevier
• Subjects: 60 APPLIED LIFE SCIENCES; Aged; ARSENIC; Arsenic methylation capacity; Arsenicals - metabolism; Arsenicals - urine; atomic absorption spectrometry; Biological and medical sciences; BLADDER; Carcinogenesis, carcinogens and anticarcinogens; carcinoma; Carcinoma, Transitional Cell - genetics; Carcinoma, Transitional Cell - metabolism; CARCINOMAS; Case-Control Studies; Chemical agents; Chemical and industrial products toxicology. Toxic occupational diseases; chronic exposure; confidence interval; dose response; Dose-Response Relationship, Drug; Female; GENES; GENOTYPE; HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY; Humans; hydrides; IL-8; INFLAMMATION; Inflammation - genetics; interleukin-6; Interleukin-6 - genetics; interleukin-8; Interleukin-8 - genetics; Male; Medical sciences; Metals and various inorganic compounds; METHYLATION; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); odds ratio; polymerase chain reaction; Polymorphism, Genetic - genetics; Regression Analysis; Risk; Socioeconomic Factors; Surveys and Questionnaires; TNF-α; Toxicology; tumor necrosis factor-alpha; Tumor Necrosis Factor-alpha - genetics; Tumors; urinary bladder neoplasms; Urologic Neoplasms - genetics; Urologic Neoplasms - metabolism; Urothelial carcinoma; Arsenic methylation capacity; Arsenic; TNF-α; IL-8; Urothelial carcinoma; Genetic variability; Toxicity; Cytokine; Genotype; Inflammation; Malignant tumor; Transitional cell carcinoma; Carcinogen; Gene; Genetics; Methylation; Tumor necrosis factor α; Interleukin 8; Cancer; Polymorphism
• ISSN: 0041-008X; 1096-0333; 1096-0333
• DOI: 10.1016/j.taap.2013.05.019

Chronic exposure to arsenic can generate reactive oxidative species, which can induce certain proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-8 (IL-8). TNF-α, IL-6 and IL-8 have been shown to be involved in the development and progression of various cancers, including bladder cancer. This study aimed to investigate the joint effect of the polymorphism of TNF-α −308 G/A, IL-6 −174 G/C, IL-8 −251 T/A and urinary arsenic profiles on urothelial carcinoma (UC) risk. 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 polymorphism of TNF-α −308 G/A, IL-6 −174 G/C and IL-8 −251 T/A was 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. We found that the TNF-α −308 A/A and IL-8 −251 T/T polymorphisms were significantly associated with UC. Moreover, significant dose–response joint effect of TNF-α −308 A/A or IL-8 −251 T/T genotypes and arsenic methylation indices were seen to affect UC risk. The present results also showed a significant increase in UC risk in subjects with the IL-8 −251 T/T genotype for each SD increase in urinary total arsenic and MMA%. In contrast, a significant decrease in UC risk was found in subjects who carried the IL-8 −251 T/T genotype for each SD increase in DMA%. •Joint effect of the TNF-α -308 A/A genotype and urinary total arsenic affected UC.•Joint effect of the IL-8 -251 T/T genotype and urinary total arsenic affected UC.•Urinary total arsenic level, TNF-α -308 A/A and IL-8 -251 T/T genotype affected UC.