Abstract
BackgroundLung cancer is one of the most preventable causes of death globally both in developed and developing countries. Although it is well established that smokers develop lung cancer, there are some smokers who are free from the disease risk. The predisposition to lung cancer is attributed to genetic polymorphisms in xenobiotic metabolizing genes. Reports on assessment of xenobiotic metabolizing genes like Cytochrome P 450 1A1 (CYP1A1), Glutathione -S -transferase M1 (GSTM1) and T1 (GSTT1) polymorphisms from India are meagre, and reports from Andhra Pradesh are lacking.Methods and resultsAssessment of polymorphisms in CYP1A1, GSTM1 and GSTT1 in NSCLC patients and healthy individuals specific to population of Andhra Pradesh, a South Indian state was attempted by multiplex PCR and RFLP, and this is the first study which tried to correlate oxidative stress with the polymorphisms in xenobiotic metabolizing genes. Results showed that CYP1A1 m1 ‘CC’ genotype was significantly associated with lung cancer susceptibility with a 2.3-fold risk, CYP1A1 m2 ‘AG’ gene polymorphisms with 8.8-fold risk and GSTT1 (−/−) genotype demonstrated a twofold risk of disease susceptibility.ConclusionsA combined role of genetic polymorphisms and smoking status can be attributed for the cause of lung cancer. Further, the association between oxidative stress and genetic polymorphisms showed a correlation between GSTT1 and super oxide dismutase activity; CYP1A1 m1, m2 and GSTT1 with glutathione peroxidase activity; CYP1A1 m1 and GSTM1 with melondialdehyde levels; and CYP1A1 m1 and GSTT1 with 8-oxo-7,8-dihydro-2′-deoxyguanosine. A higher risk of lung cancer seems to be associated with combined gene polymorphisms of phase I and phase II enzymes than that ascribed to single gene polymorphism.Electronic supplementary materialThe online version of this article (doi:10.1186/s40001-016-0209-x) contains supplementary material, which is available to authorized users.
Highlights
Lung cancer is one of the most preventable causes of death globally both in developed and developing countries
The association between oxidative stress and genetic polymorphisms showed a correlation between GSTT1 and super oxide dismutase activity; Cytochrome P 1A1 (CYP1A1) m1, m2 and GSTT1 with glutathione peroxidase activity; CYP1A1 m1 and Glutathione -S -transferase M1 (GSTM1) with melondialdehyde levels; and CYP1A1 m1 and GSTT1 with 8-oxo-7,8-dihydro-2′-deoxyguanosine
A higher risk of lung cancer seems to be associated with combined gene polymorphisms of phase I and phase II enzymes than that ascribed to single gene polymorphism
Summary
Lung cancer is one of the most preventable causes of death globally both in developed and developing countries. Genetic polymorphisms in the enzymes involved in metabolic activation and detoxification were found to immensely contribute to the risk of developing lung cancer [7] These polymorphisms cause inter-individual differences in the bio-activation and detoxification of pro-carcinogens, which are in turn responsible for the varied susceptibilities to lung cancer [8, 9]. Among the xenobiotic metabolizing enzymes, CYP1A1, GSTM1 and GSTT1 have been projected as the potential modulators of cancer susceptibility [10] These enzymes play a crucial role in bio-activation and detoxification of chemical carcinogens present in tobacco smoke, the role of Glutathione– S transferase genes in modulating the risk of cancer has been debated owing to inter-individual, geographical, ethnic and demographical differences throughout the world. A combination of GSTM1 null genotype with CYP1A1 polymorphisms augmented lung cancer risk [25, 26]
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