Genetic polymorphism of drug metabolizing enzymes in oral cancer patients and its relationship to susceptibility to carcinogenesis of oral cavity.

本研究检测了在苯并（a）芘等多环芳烃代谢活化或解毒过程中起重要作用的CYPIA 1和GST 1基因多态性在口腔鳞状细胞癌（SCC）患者中的分布情况，结果表明：（1）Ile/Ile、Ile/瓦尔和瓦尔/瓦尔基因型频率分别为0.60、0.33和0.07，与非口腔癌患者或日本健康人群相比，2.比较两组患者中至少有一个GST 1基因（GST（+））的发生率，发现两组患者中罕见的纯合子（瓦尔/瓦尔）基因型的发生率明显高于对照组。GST（-）基因在口腔癌患者和正常对照组之间的表达无显著性差异（43.3%vs46.6%）。3.在估计不同CYPIA 1基因型患者的吸烟总剂量时，瓦尔/瓦尔基因型的平均值小于其他基因型。在13.7%的下牙龈鳞癌患者中发现了吸烟诱发肺癌的高危人群，且吸烟量明显低于其他基因型。瓦尔/瓦尔纯合子也可能是吸烟诱发下牙龈癌的易感基因，提示口腔各部位的癌变机制不尽相同。

Genetic polymorphisms of CYPIA1 and GST1, which may play important roles in metabolic activation or detoxification of polycyclic aromatic hydrocarbons such as benzo (a) pyrene, were examined in the patients with oral squamous cell carcinomas (SCC).1.The frequency of genotypes, Ile/Ile, Ile/Val and Val/Val, were 0.60,0.33 and 0.07, respectively in the patients with oral SCC.Comparing with non oral cancer patients or healthy Japanese population, the number of rare homozygote (Val/Val) genotype was relatively higher than those of controls.2.Comparing the incidence of the presence of at least one GST1 gene (GST(+)) or its complete deletion (GST(-)) between oral cancer patients and controls, there was no significant difference observed (43.3% versus 46.6%).3.When the total amounts of cigarette consumption dose were estimated among patients with different CYPIA1 genotypes, the mean value of Val/Val genotype was less than those of another genotypes.4.Val/Val homozygotes, which is considered to be a high risk group against lung cancer induced by cigarette smoking, was found in 13.7% of the patients with SCC of lower gingiva and the dose of cigarette consumption in those patients were much less than those of another genotypes.In conclusion, Val/Val homozygote may be also susceptible for smoking conducted lower gingival carcinoma and it is suggested that the mechanisms of carcinogenesis are not same in the each site of the oral cavity.