4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) metabolism-related enzymes gene polymorphisms, NNK metabolites levels and urothelial carcinoma
作者： Chi-Jung Chung , Yeong-Shiau Pu , Horng-Sheng Shiue , Hui-Ling Lee , Pinpin Lin
DOI: 10.1016/J.TOXLET.2012.11.002
关键词:
摘要: Gene polymorphisms of the 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) metabolism-related enzymes-cytochrome P450 (CYP) monooxygenase 2A13 (CYP2A13) and UDP-glucuronosyltransferases (UGT)-2B7 could contribute to levels NNK-related metabolites in urine, thereby increasing susceptibility urothelial carcinoma (UC). Therefore, our study aimed evaluate roles two gene (CYP2A13 UGT2B7) NNK enzymes carcinogenesis UC Taiwan. A hospital-based pilot case-control was conducted. There were 121 cases age- sex-matched healthy participants recruited from March 2007 April 2009. Urine samples analyzed for using liquid chromatography-tandem mass spectrometry method. Genotyping conducted a polymerase chain reaction-restriction fragment length polymorphism technique. ANCOVA multivariate logistic regression applied data analyses. In controls, former smokers had significantly higher total NNAL NNAL-Gluc than never or current smokers. Subjects carrying UGT2B7 268 His/Tyr Tyr/Tyr genotype lower those His/His genotype. However, no association seen between CYP2A13 risk after adjustment age sex. Significant dose -response associations NNAL, free ratios NNAL/total NNAL-Gluc/total observed. future, large-scale studies will be required verify single nucleotide risk.
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