GSTM1 null genotype in COPD and lung cancer: evidence of a modifier or confounding effect?

Abstract

BackgroundStudies over the past two decades have reported associations between GSTM1 (glutathione S-transferase mu 1) null genotype and chronic obstructive pulmonary disease (COPD) or lung cancer. However, a modifier or confounding effect from COPD mediating the GSTM1 association with lung cancer has not been previously explored.Aim and methodsThis variant was examined in a case-control study of current or former smokers with COPD (n = 669), lung cancer (n = 454), or normal lung function (n = 488). Sex, age, and smoking history were comparable between groups.ResultsThe GSTM1 null genotype was found to be more frequent in smokers with COPD alone (odds ratio [OR] 1.30, 95% confidence interval [CI] 1.02–1.66, P = 0.031) and lung cancer (OR 1.26, 95% CI 0.96–1.65, P = 0.083) than in matched smokers with normal lung function (62%, 61%, and 56%, respectively). However, when smokers with lung cancer were subgrouped according to the presence of COPD, then the association with all COPD subjects (OR 1.34, 95% CI 1.07–1.70, P = 0.010) and with COPD and lung cancer (OR 1.50, 95% CI 1.06–2.12, P = 0.018) continued to be significant while that with lung cancer only was reduced (OR 1.11, 95% CI 0.78–1.56, P = 0.55). These associations were independent of age, sex, height, lung function, and smoking history.ConclusionFindings suggest that COPD is an important subphenotype of lung cancer and may underlie previously reported associations with the GSTM1 null genotype.