4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) metabolism-related enzymes gene polymorphisms, NNK metabolites levels and urothelial carcinoma
Journal
Toxicology Letters
Journal Volume
216
Journal Issue
1
Pages
16-22
Date Issued
2013
Author(s)
Abstract
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.
Subjects
CYP2A13; NNAL; NNK; Polymorphism; UGT2B7; Urothelial carcinoma
SDGs
Other Subjects
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
Type
journal article