Polymorphism of inflammatory genes and arsenic methylation capacity are associated with urothelial carcinoma
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- 作者：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
- 关键词：Arsenic ; Arsenic methylation capacity ; TNF-¦Á ; IL-8 ; Urothelial carcinoma
- 刊名：Toxicology and Applied Pharmacology
- 出版年：2013
- 出版时间：1 October, 2013
- 年：2013
- 卷：272
- 期：1
- 页码：30-36
- 全文大小：413 K
文摘
Chronic exposure to arsenic can generate reactive oxidative species, which can induce certain proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-¦Á), interleukin-6 (IL-6) and interleukin-8 (IL-8). TNF-¦Á, 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-¦Á ? 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-¦Á ? 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-¦Á ? 308 A/A and IL-8 ? 251 T/T polymorphisms were significantly associated with UC. Moreover, significant dose-response joint effect of TNF-¦Á ? 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 % .