Background: 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.
Purpose: 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.
Methods: 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.
Results: 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).
Conclusions: 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.
Implications: Because the power of our analyses within strata of lifetime smoking history was limited, larger studies will be needed to confirm these findings.