Tsukino H, Nakao H, Kuroda Y, Imai H, Inatomi H, Osada Y, Katoh T
Department of Public Health, Miyazaki Medical College, University of Miyazaki, 5200 Kihara, Miyazaki 889-1692, Japan.
Eur J Cancer Prev. 2004 Dec;13(6):509-14. doi: 10.1097/00008469-200412000-00008.
The objective of this study was to examine the association between the genetic polymorphism of glutathione S-transferase (GST) M1, T1 and N-acetyltransferase 2 (NAT2) genes and urothelial cancer risk in relation to smoking status. In this study, 325 Japanese patients with urothelial transitional cell carcinoma and 325 healthy controls were compared for frequencies of GSTM1, T1 and NAT2 genotypes. The frequencies of GSTM1 null genotype and NAT2 slow genotype were significantly higher in the cases than in the controls (adjusted odds ratio (OR) 1.37, 95% confidence interval (CI) 1.01-1.87, adjusted OR 3.09, 95% CI 1.69-5.63, individually). Furthermore, the risk of GSTM1 null genotype and NAT2 slow genotype was higher among smokers (adjusted OR 1.48, 95% CI 1.01-2.15, adjusted OR 4.28, 95% CI 1.96-9.36, individually). The regression analysis of cancer risk as a function of the amount of smoking showed that the susceptibility of people who had GSTM1 null genotype increased from 45 pack-years, while the susceptibility of people with NAT2 intermediate or slow genotype increased rapidly from 25 pack-years, compared with non-smokers. A multiplicative interaction between NAT2 intermediate or slow genotype and pack-years of smoking was found (P<0.001), but GSTM1 null genotype was not (P=0.06). Our results indicate that the GSTM1 null genotype and NAT2 intermediate or slow genotype are associated with an increased risk of urothelial cancer in relation to smoking amounts. Furthermore, the interaction between NAT2 intermediate or slow genotype and pack-years of smoking has a strong impact on urothelial cancer.
本研究的目的是探讨谷胱甘肽S-转移酶（GST）M1、T1基因及N-乙酰转移酶2（NAT2）基因的遗传多态性与吸烟状况相关的尿路上皮癌风险之间的关联。在本研究中，对325例日本尿路上皮移行细胞癌患者和325例健康对照者的GSTM1、T1和NAT2基因型频率进行了比较。病例组中GSTM1无效基因型和NAT2慢代谢基因型的频率显著高于对照组（调整优势比（OR）分别为1.37，95%置信区间（CI）为1.01 - 1.87；调整OR为3.09，95% CI为1.69 - 5.63）。此外，吸烟者中GSTM1无效基因型和NAT2慢代谢基因型的风险更高（调整OR分别为1.48，95% CI为1.01 - 2.15；调整OR为4.28，95% CI为1.96 - 9.36）。将癌症风险作为吸烟量的函数进行回归分析表明，与不吸烟者相比，具有GSTM1无效基因型的人群从45包年开始易感性增加，而具有NAT2中间代谢或慢代谢基因型的人群从25包年开始易感性迅速增加。发现NAT2中间代谢或慢代谢基因型与吸烟包年数之间存在相乘交互作用（P<0.001），但GSTM1无效基因型不存在此交互作用（P = 0.06）。我们的结果表明，GSTM1无效基因型和NAT2中间代谢或慢代谢基因型与吸烟量相关的尿路上皮癌风险增加有关。此外，NAT2中间代谢或慢代谢基因型与吸烟包年数之间的交互作用对尿路上皮癌有强烈影响。
