Wu C.-C.Huang Y.-K.Chung C.-J.CHAO-YUAN HUANGYEONG-SHIAU PUShiue H.-S.Lai L.-A.Lin Y.-C.Su C.-T.Hsueh Y.-M.2021-02-022021-02-0220130041-008Xhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-84882772877&doi=10.1016%2fj.taap.2013.05.019&partnerID=40&md5=9357ee374a2ab77a202cd2e32e26eea7https://scholars.lib.ntu.edu.tw/handle/123456789/544387Chronic 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%. ? 2013 Elsevier Inc.[SDGs]SDG3arsenic; interleukin 6; interleukin 8; tumor necrosis factor alpha; adult; alcohol consumption; article; controlled study; DNA polymorphism; female; gene frequency; genetic association; genotype; hospital based case control study; human; long term exposure; major clinical study; male; methylation; promoter region; risk factor; smoking; transcription initiation; transitional cell carcinoma; urine level; Arsenic; Arsenic methylation capacity; IL-8; TNF-α; Urothelial carcinoma; Aged; Arsenicals; Carcinoma, Transitional Cell; Case-Control Studies; Dose-Response Relationship, Drug; Female; Genotype; Humans; Inflammation; Interleukin-6; Interleukin-8; Male; Methylation; Middle Aged; Polymorphism, Genetic; Questionnaires; Regression Analysis; Risk; Socioeconomic Factors; Tumor Necrosis Factor-alpha; Urologic Neoplasmsjournal article10.1016/j.taap.2013.05.019237276222-s2.0-84882772877