Polymorphism of glutathione S-transferase M1 and lung cancer risk among African-Americans and Caucasians in Los Angeles County, California

Our plain-English summary of Polymorphism of glutathione S-transferase M1 and lung cancer risk among African-Americans and Caucasians in Los Angeles County, California, by S.J. London, A.K. Daly, J. Cooper, et al (Journal of the National Cancer Institute, 1995).

The study

• Authors: S.J. London, A.K. Daly, J. Cooper, W.C. Navidi, C.L. Carpenter, J.R. Idle
• Journal: Journal of the National Cancer Institute
• Published: 1995;87(16):1246-53
• Cited by: 144 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

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.

In plain English

This case-control study in Los Angeles County, California, asked whether people missing both copies of the GSTM1 gene (the "null" genotype) have a higher lung cancer risk. The authors genotyped 342 African-American and Caucasian patients with newly diagnosed lung cancer and 716 population control subjects. Interviews covered smoking and jobs with possible or probable asbestos exposure. After adjustment for age, race, sex and smoking, the null genotype had an odds ratio of 1.29 (95% CI 0.94-1.77) for all lung cancers. The null genotype was less common in African-Americans (0.27) than in Caucasians (0.52). Among smokers of under 40 pack-years the odds ratio was 1.77 (1.11-2.82). Among heavier smokers it was 0.90 (0.56-1.44). The authors found no evidence that the association varied appreciably by asbestos exposure. Odds ratios for the null genotype were 1.03 (0.68-1.55) for people reporting none of the listed asbestos-related jobs, 1.89 (1.03-3.46) for possible exposure and 1.51 (0.55-4.15) for probable exposure. The authors concluded their data did not show a major overall association. They said the lighter-smoker finding rests on small numbers and needs much larger studies.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: case-control study of patients with newly diagnosed (incident) lung cancer and population control subjects
• Who was studied: Non-Hispanic Caucasian and African-American residents of Los Angeles County aged 40-84. The authors enrolled 356 case patients (167 African-Americans, 189 Caucasians) diagnosed September 1990 to January 1994 at 35 hospitals, and 731 controls (473 Caucasians, 258 African-Americans) drawn from motor vehicle and Medicare lists. DNA adequate for genotyping was obtained from 342 cases and 716 controls.
• Exposure: The main exposure was the GSTM1 null genotype (deletion of both copies of the gene). Occupational asbestos exposure was a secondary factor, assessed from self-reported jobs. An occupational medicine physician graded these jobs as possible or probable exposure. Probable exposure included insulation, heating/cooling repair, shipyard work, construction before 1975, boilermaking and coke-oven work. People with no history of employment in any of the listed jobs were classified as not exposed. No fiber types are named.
• Main results:
  • All lung cancers combined, adjusted for age, race, sex and smoking: the odds ratio for the GSTM1 null genotype was 1.29 (95% CI 0.94-1.77). It was 0.98 (0.75-1.29) before smoking adjustment.
  • The GSTM1 null genotype was significantly less frequent among African-Americans than Caucasians (0.27 versus 0.52, p less than .001).
  • By cell type, the association was greatest for squamous cell carcinoma: odds ratio 1.57 (95% CI 0.93-2.63).
  • Smokers with less than 40 pack-years: odds ratio 1.77 (95% CI 1.11-2.82). Heavier smokers: 0.90 (0.56-1.44). The P value for the difference between strata was .045.
  • Among smokers of less than 40 pack-years, the association was most notable for squamous cell carcinoma: odds ratio 4.06 (95% CI 1.77-9.31).
  • The authors found no evidence that the GSTM1-lung cancer association varied appreciably by occupational asbestos exposure.
  • Table 2 gives odds ratios for the GSTM1 null genotype by asbestos exposure category: 1.03 (0.68-1.55) for the 'none' category, meaning no reported employment in the listed jobs; 1.89 (1.03-3.46) for possible exposure; and 1.51 (0.55-4.15) for probable exposure.
• The authors' conclusion: The authors concluded that their data were not consistent with a major association between the GSTM1 null genotype and overall lung cancer risk in this population. They also said their data gave some support for increased risk among lighter smokers.
• Limitations the authors state:
  • The lighter-smoker finding is based on relatively small numbers and needs confirmation in much larger studies.
  • Estimates within cell-type categories were unstable.
  • The response rate was somewhat low, though the authors thought it unlikely to be related to genotype.
  • Not all newly diagnosed lung cancer patients in the county were identified, and not all eligible case patients could be enrolled.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: Glutathione (GSH), Lung Cancer, Case-Control Study, Homozygous Deletion, Odds Ratio, confidence interval, Squamous Cell Carcinoma.

Related studies

• Lung cancer risk in relation to the CYP2E1 Rsa I genetic polymorphism among African-Americans and Caucasians in Los Angeles County — S.J. London, A.K. Daly, et al. (1996)
• Glutathione S-transferases GSTM1 and GSTT1 polymorphisms and asbestosis — A. Franko, M. Dodic-Fikfak, et al. (2007)
• Polymorphisms of glutathione-S-transferase M1 and manganese superoxide dismutase are associated with the risk of malignant pleural mesothelioma — S. Landi, F. Gemignani, et al. (2007)
• Genetic polymorphism for glutathione-S-transferase mu in asbestos cement workers — K. Jakobsson, A. Rannug, et al. (1994)
• Glutathione S-transferase and N-acetyltransferase genotypes and asbestos-associated pulmonary disorders — A. Hirvonen, S.T. Saarikoski, et al. (1996)
• Radiographic changes and lung function in relation to activity of the glutathione transferases theta and mu among asbestos cement workers — K. Jakobsson, A. Rannug, et al. (1995)

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