title: Polymorphism of inflammatory genes and arsenic methylation capacity are associated with urothelial carcinoma.
abstract: 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%.
authors.affiliation: School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan; Department of Urology, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan.
authors.forename: Chia-Chang
authors.initials: CC
authors.lastname: Wu
authors.forename: Yung-Kai
authors.initials: YK
authors.lastname: Huang
authors.forename: Chi-Jung
authors.initials: CJ
authors.lastname: Chung
authors.forename: Chao-Yuan
authors.initials: CY
authors.lastname: Huang
authors.forename: Yeong-Shiau
authors.initials: YS
authors.lastname: Pu
authors.forename: Horng-Sheng
authors.initials: HS
authors.lastname: Shiue
authors.forename: Li-An
authors.initials: LA
authors.lastname: Lai
authors.forename: Ying-Chin
authors.initials: YC
authors.lastname: Lin
authors.forename: Chien-Tien
authors.initials: CT
authors.lastname: Su
authors.forename: Yu-Mei
authors.initials: YM
authors.lastname: Hsueh
mesh_terms: D000368:Aged; D001152:Arsenicals / Q000378:metabolism* / Q000652:urine; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000378:metabolism*; D016022:Case-Control Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics; D016209:Interleukin-8 / Q000235:genetics; D008297:Male; D008745:Methylation; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D012044:Regression Analysis; D012306:Risk; D012959:Socioeconomic Factors; D011795:Surveys and Questionnaires; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D014571:Urologic Neoplasms / Q000235:genetics* / Q000378:metabolism*
chemical_list: D001152:Arsenicals; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha
keywords: Arsenic; Arsenic methylation capacity; IL-8; TNF-α; Urothelial carcinoma