London S J, Daly A K, Cooper J, Navidi W C, Carpenter C L, Idle J R
Division of Occupational and Environmental Medicine, University of Southern California School of Medicine, Los Angeles 90033, USA.
J Natl Cancer Inst. 1995 Aug 16;87(16):1246-53. doi: 10.1093/jnci/87.16.1246.
Glutathione S-transferase M1 (GSTM1) is active in the detoxication of a number of carcinogens, including polyaromatic hydrocarbons, such as those present in cigarette smoke. In about 30%-55% of individuals, depending on the ethnic group, there is a virtual absence of GSTM1 enzyme activity due to deletion of both copies of the GSTM1 gene (GSTM1 null genotype). This genetic polymorphism of the GSTM1 gene locus has been proposed as a risk factor for lung cancer. However, results across studies are inconsistent.
We conducted a case-control study of patients with incident lung cancer and population control subjects to examine the association between homozygous deletion of the GSTM1 gene and lung cancer risk among African-Americans and Caucasians.
At 35 hospitals in Los Angeles County, California, we identified patients with a first diagnosis of lung cancer between September 1, 1990, and January 6, 1994. Of the 859 potentially eligible case patients, 207 had died by the time their physicians had received our request for permission to contact them. We enrolled 356 eligible case patients (167 African-Americans and 189 Caucasians) and 731 eligible control subjects (258 African-Americans and 473 Caucasians, all residents of Los Angeles County). Samples of white blood cell DNA sufficient for determination of the GSTM1 genotype by a polymerase chain reaction-based assay were obtained from 342 case patients and 716 control subjects. The odds ratios (ORs) and 95% confidence intervals (CIs) for lung cancer associated with homozygous deletion of the GSTM1 gene, in total and after stratification by a number of relevant characteristics, were estimated by logistic regression analysis.
For patients with all lung cancers combined, the GSTM1 null genotype was associated with an OR of 1.29 (95% CI = 0.94-1.77). The OR was similar among African-Americans (OR = 1.20; 95% CI = 0.72-2.00) and Caucasians (OR = 1.37; 95% CI = 0.91-2.06). The association was strongest for squamous cell carcinoma (OR = 1.57; 95% CI = 0.93-2.63). We observed an OR of 1.77 (95% CI = 1.11-2.82) for the GSTM1 null genotype in relation to lung cancer risk among smokers of less than 40 pack-years, but no association among heavier smokers (OR = 0.90; 95% CI = 0.56-1.44).
Our data do not support a substantial association between homozygous deletion of the GSTM1 gene and the risk of lung cancer overall in this population. However, our data do suggest an elevated risk for lighter smokers with this genotype.
Because the power of our analyses within strata of lifetime smoking history was limited, larger studies will be needed to confirm these findings.
谷胱甘肽S-转移酶M1（GSTM1）在多种致癌物的解毒过程中发挥作用，这些致癌物包括多环芳烃，如香烟烟雾中存在的那些物质。在大约30%-55%的个体中，取决于种族群体，由于GSTM1基因的两个拷贝均缺失（GSTM1无效基因型），实际上不存在GSTM1酶活性。GSTM1基因位点的这种基因多态性已被认为是肺癌的一个危险因素。然而，各项研究的结果并不一致。
我们对新发肺癌患者和人群对照进行了一项病例对照研究，以检验GSTM1基因纯合缺失与非裔美国人和白种人肺癌风险之间的关联。
在加利福尼亚州洛杉矶县的35家医院，我们确定了1990年9月1日至1994年1月6日期间首次诊断为肺癌的患者。在859名潜在符合条件的病例患者中，有207人在其医生收到我们请求联系他们的许可时已经死亡。我们纳入了356名符合条件的病例患者（167名非裔美国人、189名白种人）和731名符合条件的对照对象（258名非裔美国人、473名白种人，均为洛杉矶县居民）。通过基于聚合酶链反应的检测方法，从342名病例患者和716名对照对象中获取了足以确定GSTM1基因型的白细胞DNA样本。通过逻辑回归分析，估计了GSTM1基因纯合缺失与肺癌相关的比值比（OR）及95%置信区间（CI），包括总体情况以及按一些相关特征分层后的情况。
对于所有合并的肺癌患者，GSTM1无效基因型的OR为1.29（95%CI=0.94-1.77）。在非裔美国人（OR=1.20；95%CI=0.72-2.00）和白种人（OR=1.37；95%CI=0.91-2.06）中，该OR相似。这种关联在鳞状细胞癌中最强（OR=1.57；95%CI=0.93-2.63）。对于吸烟量小于40包年的吸烟者，GSTM1无效基因型与肺癌风险相关的OR为1.77（95%CI=1.11-2.82），但在吸烟量更大的吸烟者中无关联（OR=0.90；95%CI=0.56-1.44）。
我们的数据不支持GSTM1基因纯合缺失与该人群总体肺癌风险之间存在实质性关联。然而，我们的数据确实表明，具有这种基因型的轻度吸烟者风险升高。
由于我们在终身吸烟史分层内的分析效能有限，需要更大规模的研究来证实这些发现。
