Kihara M, Kihara M, Noda K
Department of Epidemiology, Kanagawa Cancer Center Research Institute, Yokohama, Japan.
Carcinogenesis. 1994 Feb;15(2):415-8. doi: 10.1093/carcin/15.2.415.
Recently, homozygous gene deletion of GSTM1, one of the Mu class glutathione S-transferase isozymes, was found to occur in approximately half of the population of various ethnic origins and has been implicated in tobacco-related carcinogenesis. In the present study we evaluated the risk of GSTM1 null genotype for lung cancer in relation to the extent of tobacco smoke exposure in 178 lung cancer patients (157 males, 21 females) and 201 healthy controls (140 males, 61 females), who were all Japanese and current smokers aged < or = 69 at the time of diagnosis. GSTM1 genotype was determined by polymerase chain reaction. We found GSTM1 gene to be lacking in 45.3% of the control population and demonstrated that the null genotype was aggregated a lot more in the squamous and small cell carcinoma groups (63-64%) than the control group but slightly more in the adenocarcinoma group (54.3%). Furthermore, when male patients and controls were analysed in relation to the degrees (< 800, 800-1200 and > or = 1200) of smoking index (sigma (cigarettes smoked per day) x (years of smoking)], the proportion of GSTM1 null genotype was found to increase progressively in the squamous and small cell carcinoma groups from 42-50% (odds ratio 0.8-1.3) in the patients with smoking index < 800 to 72-75% (odds ratio 3.1-3.7) in the patients with smoking index > or = 1200, while it was unrelated in the adenocarcinoma (50-55%, odds ratio 1.2-1.5) and in the control groups (42-48%). These results support the hypothesis that the GSTM1 null genotype is one of the genetic traits for smoking-related lung cancers, the risk of which, however, appears to be dependent on the extent of tobacco smoke exposure.
近期研究发现，微粒体谷胱甘肽S-转移酶同工酶之一的GSTM1基因纯合缺失在不同种族约半数人群中存在，并与烟草相关致癌作用有关。在本研究中，我们评估了178例肺癌患者（157例男性，21例女性）和201例健康对照者（140例男性，61例女性）中GSTM1基因缺失型对肺癌发生风险的影响，所有研究对象均为日本人且为现吸烟者，诊断时年龄≤69岁。采用聚合酶链反应检测GSTM1基因型。我们发现对照组中45.3%的个体GSTM1基因缺失，且显示基因缺失型在鳞状细胞癌和小细胞癌组（63%-64%）中的聚集程度远高于对照组，但在腺癌组中略高（54.3%）。此外，当按照吸烟指数（每日吸烟支数×吸烟年数）的不同程度（<800、800-1200和≥1200）对男性患者和对照者进行分析时，发现鳞状细胞癌和小细胞癌组中GSTM1基因缺失型的比例从吸烟指数<800的患者中的42%-50%（比值比0.8-1.3）逐渐增加至吸烟指数≥1200的患者中的72%-75%（比值比3.1-3.7），而在腺癌组（50%-55%，比值比1.2-1.5）和对照组（42%-48%）中则无相关性。这些结果支持了GSTM1基因缺失型是吸烟相关肺癌的遗传特征之一这一假说，但其风险似乎取决于烟草烟雾暴露程度。
