Glutathione S-Transferase M1 (GSTM1) Polymorphisms and Lung Cancer: A Literature-based Systematic HuGE Review and Meta-Analysis

• Published in: American journal of epidemiology Vol. 167; no. 7; pp. 759 - 774
• Main Authors: Carlsten, C., Sagoo, G. S., Frodsham, A. J., Burke, W., Higgins, J. P. T.
• Format: Journal Article
• Language: English
• Published: Cary, NC Oxford University Press 01-04-2008; Oxford Publishing Limited (England)
• Subjects: Analysis. Health state; Biological and medical sciences; Enzymes; Epidemiology; General aspects; Genetic Predisposition to Disease; genetics; genome; Genomics; Genotype; glutathione S-transferase M1; glutathione transferase; Glutathione Transferase - genetics; GSTM1; human; Humans; Lung cancer; lung neoplasms; Lung Neoplasms - enzymology; Lung Neoplasms - epidemiology; Lung Neoplasms - genetics; Medical sciences; Meta-analysis; Miscellaneous; Pneumology; Polymorphism; Polymorphism, Genetic; Public health. Hygiene; Public health. Hygiene-occupational medicine; Risk Factors; Tumors of the respiratory system and mediastinum; glutathione transferase; epidemiology; genome; genetics; lung neoplasms; glutathione; transferase M1; meta-analysis; human; Human; Lung disease; Enzyme; Respiratory disease; Transferases; Lung cancer; Genomics; Evidence-based practice; Systematic review; epidemiology; genetics; genome; Malignant tumor; human; glutathione S-transferase M1; glutathione transferase; GSTM1; lung neoplasms; meta-analysis; Epidemiology; Evidence-based medicine; Metaanalysis; Scientific literature; Glutathione transferase; Bronchus disease; Genetics; Genome; Public health; Cancer; Polymorphism
• ISSN: 0002-9262; 1476-6256
• DOI: 10.1093/aje/kwm383

Multiple genes have been studied for potential associations with lung cancer. The gene most frequently associated with increased risk has been glutathione S-transferase M1 (GSTM1). The glutathione S-transferase enzyme family is known to catalyze detoxification of electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. In this review, the authors summarize the available evidence associating lung cancer with the GSTM1 gene. They describe results from an updated meta-analysis of 98 published genetic association studies investigating the relation between the GSTM1 null variant and lung cancer risk including 19,638 lung cancer cases and 25,266 controls (counting cases and controls in each study only once). All studies considered, the GSTM1 null variant was associated with an increased risk of lung cancer (odds ratio (OR) = 1.22, 95% confidence interval (CI): 1.14, 1.30), but no increase in risk was seen (OR = 1.01, 95% CI: 0.91, 1.12) when only the five largest studies (>500 cases each) were considered. Furthermore, while GSTM1 null status conferred a significantly increased risk of lung cancer to East Asians (OR = 1.38, 95% CI: 1.24, 1.55), such a genotype did not confer increased risk to Caucasians. More data regarding the predictive value of GSTM1 genetic testing are needed before population-based testing may be reasonably considered.