Journal article
The UDP-glucuronosyltransferase 2B17 gene deletion polymorphism : Sex-specific association with urinary 4-(methylnitrosamino)-1 -(3-pyridyl)-1 -butanol glucuronidation phenotype and risk for lung cancer
Cancer epidemiology, biomarkers & prevention, Vol.16(4), pp.823-828
2007
Handle:
https://hdl.handle.net/2376/112542
PMID: 17416778
Abstract
4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone is a potent and abundant procarcinogen found in tobacco smoke, and glucuronidation of its major metabolite, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), by UDP-glucuronosyltransferases (UGT) including UGT2B17 is an important mechanism for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone detoxification. Both copies of the UGT2B17 gene are deleted in ∼10% of Whites and the deletion is associated with a reduction in NNAL glucuronidation activity in vitro. In this study, we examined the effects of the UGT2B17 deletion (0/0) on NNAL glucuronidation rates in a sample of 82 healthy cigarette smokers and further examined its effects on lung cancer risk in a separate case-control study. In the healthy smokers study, a lower urinary ratio of NNAL-glucuronide to NNAL was observed in women with the UGT2B17 deletion (0/0) as compared with women with either the wild-type or heterozygous genotypes (P = 0.058). There were no significant differences in this ratio by genotype in men (P = 0.597). In the case-control study of 398 lung cancer patients and 697 community controls, the UGT2B17 deletion (0/0) was associated with a significant increase in risk of lung cancer in women (odds ratio, 2.0; 95% confidence interval, 1.01-4.0). The risk for the subset of women with lung adenocarcinoma was 2.8 (95% confidence interval, 1.2-6.3). The deletion was not associated with other lung histologic types in women and was not associated with the risk for any lung histologic types in men. The association of the UGT2B17 deletion with increased lung adenocarcinoma in women is consistent with its association with decreased NNAL glucuronidation rates in women and with studies showing that NNAL is a selective inducer of lung adenocarcinoma in experimental animals.
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Details
- Title
- The UDP-glucuronosyltransferase 2B17 gene deletion polymorphism : Sex-specific association with urinary 4-(methylnitrosamino)-1 -(3-pyridyl)-1 -butanol glucuronidation phenotype and risk for lung cancer
- Creators
- Carla J GALLAGHER - Department of Health Evaluation Sciences, Penn State Cancer Institute, Penn State College of Medicine, Hershey, Pennsylvania, United StatesJoshua E MUSCAT - Department of Health Evaluation Sciences, Penn State Cancer Institute, Penn State College of Medicine, Hershey, Pennsylvania, United StatesAmy N HICKS - Department of Health Evaluation Sciences, Penn State Cancer Institute, Penn State College of Medicine, Hershey, Pennsylvania, United StatesYAN ZHENG - Department of Pharmacology, Cancer Prevention and Control Program, Penn State Cancer Institute, Penn State College of Medicine, Hershey, Pennsylvania, United StatesAnne-Marie DYER - Department of Health Evaluation Sciences, Penn State Cancer Institute, Penn State College of Medicine, Hershey, Pennsylvania, United StatesGary A CHASE - Department of Health Evaluation Sciences, Penn State Cancer Institute, Penn State College of Medicine, Hershey, Pennsylvania, United StatesJohn RICHIE - Department of Health Evaluation Sciences, Penn State Cancer Institute, Penn State College of Medicine, Hershey, Pennsylvania, United StatesPhilip LAZARUS - Department of Health Evaluation Sciences, Penn State Cancer Institute, Penn State College of Medicine, Hershey, Pennsylvania, United States
- Publication Details
- Cancer epidemiology, biomarkers & prevention, Vol.16(4), pp.823-828
- Academic Unit
- Department of Pharmaceutical Sciences
- Publisher
- American Association for Cancer Research; Philadelphia, PA
- Identifiers
- 99900547826801842
- Language
- English
- Resource Type
- Journal article