4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) metabolism-related enzymes gene polymorphisms, NNK metabolites levels and urothelial carcinoma

Chi Jung Chung, Yeong Shiau Pu, Horng Sheng Shiue, Hui Ling Lee, Pinpin Lin, Hsiu Yuan Yang, Chien-Tien Su, Yu-Mei Hsueh

研究成果: 雜誌貢獻文章

6 引文 (Scopus)

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.
原文英語
頁(從 - 到)16-22
頁數7
期刊Toxicology Letters
216
發行號1
DOIs
出版狀態已發佈 - 一月 2013

指紋

Metabolites
Polymorphism
Metabolism
Genes
Carcinoma
Mixed Function Oxygenases
Enzymes
Association reactions
Glucuronosyltransferase
Genotype
Urine
Polymerase chain reaction
Liquid chromatography
Risk Adjustment
Cytochrome P-450 Enzyme System
Mass spectrometry
Logistics
Tandem Mass Spectrometry
Taiwan
Liquid Chromatography

Keywords

  • CYP2A13
  • NNAL
  • NNK
  • Polymorphism
  • UGT2B7
  • Urothelial carcinoma

ASJC Scopus subject areas

  • Toxicology

引用此文

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) metabolism-related enzymes gene polymorphisms, NNK metabolites levels and urothelial carcinoma. / Chung, Chi Jung; Pu, Yeong Shiau; Shiue, Horng Sheng; Lee, Hui Ling; Lin, Pinpin; Yang, Hsiu Yuan; Su, Chien-Tien; Hsueh, Yu-Mei.

於: Toxicology Letters, 卷 216, 編號 1, 01.2013, p. 16-22.

研究成果: 雜誌貢獻文章

Chung, Chi Jung ; Pu, Yeong Shiau ; Shiue, Horng Sheng ; Lee, Hui Ling ; Lin, Pinpin ; Yang, Hsiu Yuan ; Su, Chien-Tien ; Hsueh, Yu-Mei. / 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) metabolism-related enzymes gene polymorphisms, NNK metabolites levels and urothelial carcinoma. 於: Toxicology Letters. 2013 ; 卷 216, 編號 1. 頁 16-22.
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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.",
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AU - Shiue, Horng Sheng

AU - Lee, Hui Ling

AU - Lin, Pinpin

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