ArticleCancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology2016
Association between Glucuronidation Genotypes and Urinary NNAL Metabolic Phenotypes in Smokers.
Article in Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 22 citations in OpenAlex.
- Siglec-15 Expression in Gastric Carcinoma and Its Association With Clinicopathological Variables.World journal of oncology · 2026Article
- Article
- Suppressing the activation of protein kinase A as a DNA damage-independent mechanistic lead for dihydromethysticin prophylaxis of NNK-induced lung carcinogenesis.Carcinogenesis · 2022Article
- Characterization of adductomic totality of NNK, (R)-NNAL and (S)-NNAL in A/J mice, and their correlations with distinct lung carcinogenicity.Carcinogenesis · 2022Article
- Alkylating and oxidative stresses in smoking and non-smoking patients with COPD: Implications for lung carcinogenesis.Free radical biology & medicine · 2021Article
- Oral Dosing of Dihydromethysticin Ahead of Tobacco Carcinogen NNK Effectively Prevents Lung Tumorigenesis in A/J Mice.Chemical research in toxicology · 2020Article
- Role of l- and d-Menthol in the Glucuronidation and Detoxification of the Major Lung Carcinogen, NNAL.Drug metabolism and disposition: the biological fate of chemicals · 2019Article
- Prominent Stereoselectivity of NNAL Glucuronidation in Upper Aerodigestive Tract Tissues.Chemical research in toxicology · 2019Article
- Quantitative characterization of UDP-glucuronosyltransferase 2B17 in human liver and intestine and its role in testosterone first-pass metabolism.Biochemical pharmacology · 2018Article
- A Comparison of Direct and Indirect Analytical Approaches to Measuring Total Nicotine Equivalents in Urine.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2018Article
- Hepatic Abundance and Activity of Androgen- and Drug-Metabolizing Enzyme UGT2B17 Are Associated with Genotype, Age, and Sex.Drug metabolism and disposition: the biological fate of chemicals · 2018Article
- Influence of UGT2B10 Genotype on Urinary Excretion of 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol- N-glucuronide by African American Smokers.Chemical research in toxicology · 2018Article
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4 authors at 1 institution in 2 countries.
Funding
Abstract
backgroundThe most abundant and potent carcinogenic tobacco-specific nitrosamine in tobacco and tobacco smoke is 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). In vivo, NNK is rapidly metabolized to both the (R)- and (S)-enantiomers of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), which possesses similar carcinogenic properties as NNK. The major detoxification pathway for both NNAL enantiomers is glucuronidation by UDP-glucuronosyltransferase (UGT) enzymes including UGT2B10 and UGT2B17. The goal of the present study was to directly examine the role of UGT genotypes on urinary levels of NNAL glucuronides in smokers.
methodsNNAL-N-Gluc, (R)-NNAL-O-Gluc, (S)-NNAL-O-Gluc, and free NNAL were simultaneously and directly quantified in the urine of smokers by LC/MS analysis. Genotypes were determined by TaqMan assay using genomic DNA.
resultsThe functional knockout polymorphism in the UGT2B10 gene at codon 67 (Asp>Tyr) was significantly (P < 0.0001) associated with a 93% decrease in creatinine-adjusted NNAL-N-Gluc. The polymorphic whole-gene deletion of the UGT2B17 gene was associated with significant (P = 0.0048) decreases in the levels of creatinine-adjusted (R)-NNAL-O-Gluc, with a 32% decrease in the levels of urinary (R)-NNAL-O-Gluc/(S)-NNAL-O-Gluc among subjects with the UGT2B17 (*2/*2) genotype as compared to subjects with the UGT2B17 (*1/*1) genotype.
conclusionsThese results suggest that functional polymorphisms in UGT2B10 and UGT2B17 are associated with a reduced detoxification capacity against NNAL and may therefore affect individual cancer risk upon exposure to tobacco. IMPACT: This is the first report to clearly demonstrate strong genotype-phenotype associations between both the UGT2B10 codon 67 Asp<Tyr genotype and urinary NNAL-N-Gluc levels and between the UGT2B17 copy number variant and urinary (R)-NNAL-O-Gluc levels in smokers. Cancer Epidemiol Biomarkers Prev; 25(7); 1175-84. ©2016 AACR.
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