25 Citations (Scopus)


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%.

Original languageEnglish
Pages (from-to)30-36
Number of pages7
JournalToxicology and Applied Pharmacology
Issue number1
Publication statusPublished - Oct 1 2013


  • Arsenic
  • Arsenic methylation capacity
  • IL-8
  • TNF-α
  • Urothelial carcinoma

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology


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