Genetic Polymorphism in the Phase II (GSTM1 & GSTT1 & GSTP1) Detoxification Genes with Risk for Occurrence Lung Cancer and Its Association With Clinico-pathological Features In North Indian Population

Abstract

Glutathione transferases (GSTs), a multiple gene family of phase II enzymes, catalyses detoxification of endogenous compounds with glutathione and thus protects macromolecules from damage caused by carcinogenic agents. We carried out the study to investigate the potential role of GSTT1, GSTM1 and GSTP1 polymorphisms in likelihood of development of lung cancer, either separately or in combination. This case-control study consisted of 270 cases with lung cancer and 270 age and gender matched cancer free controls from Department of Pulmonary Medicine, Post Graduate Institute of Medical Education and Research (PGIMER) Chandigarh, India. The frequencies for the GSTM1 null genotypes were 49.6 and 38.14 % among cases and controls, and for the GSTT1 null genotype 18.52 and 13.70 % respectively. The distribution of the GSTP1 Ile/Ile, Ile/Val and Val/Val genotypes was 83.33, 14.82 and 1.85 % in cases and 86.30, 11.85 and 1.85% in controls respectively.. In our studies GSTM1 null genotype showed an elevated risk for lung cancer (OR= 1.65, 95%CI=1.16-2.3, p=0.005) but neither GSTT1 null genotype nor the genotypes of GSTP1 showed increased risk for overall lung cancer but when analysis was done for histological subtypes, GSTT1 and GSTM1 null genotype showed a significant risk for developing ADCC (OR=2.32, 95%CI =1.27-4.25, p=0.006; OR=2, 95%CI =1.21-3.3, p=0.006). When analyzed in combinations, GSTM1, GSTT1 and GSTP1 genotypes did show an association with overall lung cancer and further these combinations had an elevated risk for ADCC and SCLC. Smoking is considered to be associated with lung cancer but in our case none of the genotypes of GSTM1, GSTT1 and GSTP1 suggested any relationship between smoking and lung cancer. Whereas, GSTM1 null genotype showed an elevated risk for lung cancer in case of non smokers (OR=3.03, 95% CI- 1.48-6.39, p=0.002). The genotypes of three GSTs in triplet combinations did not show any significant relationship with overall lung cancer.