BACKGROUND: The enzyme uridine diphospho glucuronosyltansferase 2B17 (UGT2B17) glucuronidates several endogenous and exogenous compounds, including carcinogens from tobacco smoke like 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanl (NNAL). UGT2B17 shows a remarkable copy number variation (CNV) and an association between deletion genotype and increased risk of lung adenocarcinoma in women has been previously reported. METHODS: We investigated the UGT2B17 CNV by PCR in 453 Austrian lung cancer patients and in 449 healthy donors and analyzed the impact on lung cancer susceptibility and outcome. RESULTS: Copy numbers of UGT2B17 were 44.4% (+/+), 42.2% (+/-) and 13.5% (-/-) in lung cancer patients and 43.0% (+/+), 46.3% (+/-) and 10.7% (-/-) among healthy donors. The null genotype was not significantly more frequent among women with adenocarcinoma compared to healthy women (p=0.59). There was no association with overall survival (p=0.622) and no significant sex-associated (p=0.423) or histology-related impact on development of lung cancer. CONCLUSION: UGT2B17 deletion genotype was not associated with a significant risk for lung cancer development or outcome in our Central European patient cohort. Our study indicates that UGT2B17 is not a crucial factor in lung carcinogenesis among Caucasians and shows the importance of investigating such markers in large cohorts from different populations.
BACKGROUND: The enzyme uridine diphospho glucuronosyltansferase 2B17 (UGT2B17) glucuronidates several endogenous and exogenous compounds, including carcinogens from tobacco smoke like 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanl (NNAL). UGT2B17 shows a remarkable copy number variation (CNV) and an association between deletion genotype and increased risk of lung adenocarcinoma in women has been previously reported. METHODS: We investigated the UGT2B17 CNV by PCR in 453 Austrian lung cancerpatients and in 449 healthy donors and analyzed the impact on lung cancer susceptibility and outcome. RESULTS: Copy numbers of UGT2B17 were 44.4% (+/+), 42.2% (+/-) and 13.5% (-/-) in lung cancerpatients and 43.0% (+/+), 46.3% (+/-) and 10.7% (-/-) among healthy donors. The null genotype was not significantly more frequent among women with adenocarcinoma compared to healthy women (p=0.59). There was no association with overall survival (p=0.622) and no significant sex-associated (p=0.423) or histology-related impact on development of lung cancer. CONCLUSION:UGT2B17 deletion genotype was not associated with a significant risk for lung cancer development or outcome in our Central European patient cohort. Our study indicates that UGT2B17 is not a crucial factor in lung carcinogenesis among Caucasians and shows the importance of investigating such markers in large cohorts from different populations.
Authors: Shannon Kozlovich; Gang Chen; Christy J W Watson; William J Blot; Philip Lazarus Journal: Drug Metab Dispos Date: 2019-10-02 Impact factor: 3.922
Authors: Liwen Hu; Yuanyuan Wu; Xingying Guan; Yan Liang; Xinyue Yao; Deli Tan; Yun Bai; Gang Xiong; Kang Yang Journal: Am J Cancer Res Date: 2015-09-15 Impact factor: 6.166
Authors: María Santos; Mikko Niemi; Masahiro Hiratsuka; Masaki Kumondai; Magnus Ingelman-Sundberg; Volker M Lauschke; Cristina Rodríguez-Antona Journal: Genet Med Date: 2017-10-26 Impact factor: 8.822