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Appl Clin Genet. 2011 Sep 13;4:137-44. doi: 10.2147/TACG.S21517. Print 2011.

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

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1
Schools of Biological Science and Health Sciences, University of Auckland ; Department of Medicine, Auckland City Hospital, Auckland, New Zealand.

Abstract

BACKGROUND:

Studies 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 METHODS:

This 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.

RESULTS:

The 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.

CONCLUSION:

Findings suggest that COPD is an important subphenotype of lung cancer and may underlie previously reported associations with the GSTM1 null genotype.

KEYWORDS:

GSTM1; association study; chronic obstructive pulmonary disease; copy number variant; lung cancer; polymorphism

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