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

Chia Chang Wu, Yung Kai Huang, Chi Jung Chung, Chao Yuan Huang, Yeong Shiau Pu, Horng Sheng Shiue, Li An Lai, Ying-Chin Lin, Chien-Tien Su, Yu Mei Hsueh

研究成果: 雜誌貢獻文章同行評審

29 引文 斯高帕斯(Scopus)

摘要

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%.
原文英語
頁(從 - 到)30-36
頁數7
期刊Toxicology and Applied Pharmacology
272
發行號1
DOIs
出版狀態已發佈 - 10月 1 2013

Keywords

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

ASJC Scopus subject areas

  • 藥理
  • 毒理學

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