Giannakopoulos Xenofon, Charalabopoulos Konstantin, Baltogiannis Dimitrios, Chatzikiriakidou Anthi, Alamanos Yannis, Georgiou Ioannis, Evangelou Angelos, Agnantis Niki, Sofikitis Nikolaos
Department of Urology-Laboratory of Molecular Urology, Ioannina University School of Medicine, 451 10-Ioannina, Greece.
Anticancer Res. 2002 Nov-Dec;22(6B):3801-4.
N-acetyltransferase-2 (NAT-2) and Glutathione-S-transferase M1 and T1 (GSTM1 and GSTT1) polymorphism have been implicated in the detoxification of urothelial carcinogens, such as arylamines and polycyclic aromatic hydrocarbons. The results of epidemiological studies examining the role of NAT-2, GSTM1 and GSTT1 genotypes on the risk factors for bladder cancer were controversial, although suggesting that there may be an increased risk of the disease associated with these genotypes. The aim of the present study was to examine the independent effect and a possible interaction of NAT-2, GSTM1 and GSTT1 genotypes on the risk of bladder carcinogenesis, in the frame of a case-control study. We also investigated the possible association of specific genotype combinations with more aggressive disease in terms of tumor grading and local staging at the time of initial diagnosis. Between August 1996 and May 1998, 89 newly-diagnosed bladder cancer patients (transitional cell type) and 147 controls were included in the study. All patients were selected at the time of first diagnosis, done in the Department of Urology at the University Hospital of Ioannina, in north-western Greece. GSTM1 and NAT-2 deficient genotypes were found to be independently associated with the risk of bladder cancer (odds ratios 2.87 and 2.64, respectively). The GSTT1 genotype did not present any significant association with bladder cancer risk. We did not find a significant interaction between genotypes. These results could be explained by the independent activity of the two enzymes. Studies that will simultaneously examine the role of several genetic and environmental factors involved in bladder carcinogenesis are needed to give a global picture for the risk factors of bladder cancer and their potential interaction.
N-乙酰基转移酶-2（NAT-2）以及谷胱甘肽-S-转移酶M1和T1（GSTM1和GSTT1）基因多态性与尿路上皮致癌物（如芳胺和多环芳烃）的解毒作用有关。尽管有研究表明这些基因型可能会增加患膀胱癌的风险，但关于NAT-2、GSTM1和GSTT1基因型在膀胱癌危险因素中作用的流行病学研究结果存在争议。本研究的目的是在病例对照研究框架内，探讨NAT-2、GSTM1和GSTT1基因型对膀胱癌发生风险的独立影响以及可能的相互作用。我们还研究了在初次诊断时，特定基因型组合与更具侵袭性疾病（根据肿瘤分级和局部分期）之间的可能关联。1996年8月至1998年5月，89例新诊断的膀胱癌患者（移行细胞型）和147例对照被纳入研究。所有患者均在希腊西北部约阿尼纳大学医院泌尿外科首次诊断时入选。发现GSTM1和NAT-2缺陷基因型与膀胱癌风险独立相关（优势比分别为2.87和2.64）。GSTT1基因型与膀胱癌风险无显著关联。我们未发现基因型之间存在显著相互作用。这些结果可以通过两种酶的独立活性来解释。需要同时研究参与膀胱癌发生的多种遗传和环境因素作用的研究，以全面了解膀胱癌的危险因素及其潜在相互作用。
