The presence of the UGT2B17 gene is associated with lung cancer in male Chinese Han smokers

The genetic impact of UGT2B17 gene copy number variation (CNV) on tobacco-smoking related cancers is of interest since this enzyme plays an important role in glucuronidation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a major metabolite from the nicotine-derived tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). This is an important mechanism for NNK detoxification. The UGT2B17 gene varies in copy number from zero to two per individual in humans and this CNV was genotyped in 148 lung cancer and 92 control Chinese Han samples by a PCR-based method. The frequency of the UGT2B17 undeleted allele was higher in lung cancer patients than in controls but not significantly so (p = 0.042, OR 1.6; 95% CI: 0.97–2.57); however, in smokers with lung cancer its frequency is significantly higher than in controls, (p = 0.016, OR 1.8; 95% CI: 1.08–3.18). The undeleted allele was also significantly higher in the male lung cancer group (p = 0.015, OR 1.86; 95% CI: 1.09–3.16), and even higher in the male smoker lung cancer group (p = 0.004, OR 2.23; 95% CI: 1.27–3.89). In subsets of the male smoker lung cancer group defined by their histopathology, the undeleted allele was significantly higher in squamous cell carcinoma (p = 0.026, OR 2.09; 95% CI: 1.06–4.10). These results show that UGT2B17 copy number is associated with male smoker lung cancer in China, especially squamous cell carcinoma.