Glutathione S-transferase M1 polymorphism and lung cancer risk in African-Americans

• Published in: Carcinogenesis (New York) 2000-11, Vol.21 (11), p.1971-1975
• Main Authors: Ford, Jean G., Li, Yongliang, O'Sullivan, Mary Margaret, Demopoulos, Rita, Garte, Seymour, Taioli, Emanuela, Brandt-Rauf, Paul W.
• Format: Article
• Language: English
• Subjects: African Americans; African Continental Ancestry Group - genetics; Biological and medical sciences; Case-Control Studies; confidence interval; Female; Gene Deletion; glutathione S-transferase M1; Glutathione Transferase - genetics; GSTM1; Humans; Lung Neoplasms - enzymology; Lung Neoplasms - genetics; Male; Medical sciences; Middle Aged; odds ratio; PAH; PCR; Pneumology; polycyclic aromatic hydrocarbon; polymerase chain reaction; Polymorphism, Genetic; Risk Factors; Smoking - adverse effects; squamous cell carcinoma; Tumors of the respiratory system and mediastinum
• ISSN: 0143-3334; 1460-2180; 1460-2180
• DOI: 10.1093/carcin/21.11.1971

Glutathione S-transferase M1 (GSTM1) can detoxify many carcinogens, including polycyclic aromatic hydrocarbons such as those from cigarette smoke. Though a number of studies have been published about the association between GSTM1 polymorphism and lung cancer, this association has received limited attention in the African-American population. We conducted a case–control study to investigate the role of GSTM1 polymorphism in the development of lung cancer in African-Americans. Specimens of DNA from 117 lung cancer cases and 120 controls were assayed for detection of GSTM1 genotype by polymerase chain reaction (PCR). The odds ratios (ORs) and 95% confidence intervals (CIs) for lung cancer associated with homozygous deletion of the GSTM1 gene and other risk factors were estimated by logistic regression. Thirty-seven of the 117 cases (31.6%) and 24 of the 120 controls (20.0%) had the GSTM1 null genotype; the OR was 2.10 (95% CI 1.07–4.11) after adjustment for age, gender and smoking. The association was higher for squamous cell carcinoma (OR 2.98, 95% CI 1.09–8.19) than for adenocarcinoma (OR 1.95, 95% CI 0.81–4.66). We observed a stronger association between GSTM1 null genotype and lung cancer among heavy smokers with ≥30 pack-years (OR 4.35, 95% CI 1.16–16.23). This association was also found in squamous cell carcinoma (OR 6.26, 95% CI 1.31–29.91). In the analysis combining GSTM1 polymorphism and smoking, smokers with the null genotype had high risk (OR 8.19, 95% CI 2.35–28.62) compared with non-smokers with the wild-type genotype, and the risk increased with smoking cigarette pack-years (P = 0.0001 for trend). Our results suggest that GSTM1 polymorphism plays a role in the development of lung cancer and modifies the risk for smoking-related lung cancer in African-Americans.