https://scholars.lib.ntu.edu.tw/handle/123456789/544400
標題: | 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) metabolism-related enzymes gene polymorphisms, NNK metabolites levels and urothelial carcinoma | 作者: | Chung C.-J. YEONG-SHIAU PU Shiue H.-S. Lee H.-L. Lin P. Yang H.-Y. Su C.-T. Hsueh Y.-M. |
關鍵字: | CYP2A13; NNAL; NNK; Polymorphism; UGT2B7; Urothelial carcinoma | 公開日期: | 2013 | 卷: | 216 | 期: | 1 | 起(迄)頁: | 16-22 | 來源出版物: | Toxicology Letters | 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 the levels of NNK-related metabolites in urine, thereby increasing the susceptibility to urothelial carcinoma (UC). Therefore, our study aimed to evaluate the roles of two gene polymorphisms (CYP2A13 and UGT2B7) of NNK metabolism-related enzymes in the carcinogenesis of UC in Taiwan. A hospital-based pilot case-control study was conducted. There were 121 UC cases and 121 age- and sex-matched healthy participants recruited from March 2007 to April 2009. Urine samples were analyzed for NNK-related metabolites using the liquid chromatography-tandem mass spectrometry method. Genotyping was conducted using a polymerase chain reaction-restriction fragment length polymorphism technique. ANCOVA and multivariate logistic regression were applied for data analyses. In healthy controls, former smokers had significantly higher total NNAL and higher NNAL-Gluc than never smokers or current smokers. Subjects carrying the UGT2B7 268 His/Tyr or Tyr/Tyr genotype had significantly lower total NNAL than those carrying His/His genotype. However, no association was seen between gene polymorphisms of CYP2A13 and UGT2B7 and UC risk after adjustment for age and sex. Significant dose -response associations between total NNAL, free NNAL, the ratios of free NNAL/total NNAL and NNAL-Gluc/total NNAL and UC risk were observed. In the future, large-scale studies will be required to verify the association between the single nucleotide polymorphisms of NNK metabolism-related enzymes and UC risk. ? 2012 Elsevier Ireland Ltd. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84870539785&doi=10.1016%2fj.toxlet.2012.11.002&partnerID=40&md5=91b866bf04aa52265eca8a64fc67fdde https://scholars.lib.ntu.edu.tw/handle/123456789/544400 |
ISSN: | 0378-4274 | DOI: | 10.1016/j.toxlet.2012.11.002 | SDG/關鍵字: | 4 (methylnitrosamino) 1 (3 pyridyl) 1 butanone; cytochrome P450; cytochrome p450 2a13; glucuronosyltransferase 2B7; unclassified drug; adult; analysis of covariance; article; cancer risk; carcinogenesis; case control study; controlled study; female; genetic association; genetic polymorphism; genotype; human; liquid chromatography; major clinical study; male; metabolite; multivariate logistic regression analysis; pilot study; polymerase chain reaction; priority journal; restriction fragment length polymorphism; smoking; Taiwan; tandem mass spectrometry; transitional cell carcinoma; urine level; Aryl Hydrocarbon Hydroxylases; Carcinoma; Case-Control Studies; Female; Gene Expression Regulation, Enzymologic; Genotype; Glucuronosyltransferase; Humans; Male; Middle Aged; Nitrosamines; Pilot Projects; Polymorphism, Genetic; Risk Factors; Smoking; Urologic Neoplasms; Urothelium |
顯示於: | 醫學系 |
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