Association of CYP1A1, GSTM1 and GSTT1 gene polymorphisms with risk of non-small cell lung cancer in Andhra Pradesh region of South India

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.

Association of 12 polymorphic variants conferring genetic risk to lung cancer in Indian population: An extensive meta‐analysis

“…Thus, identification of smokers with high risks of developing lung cancer has substantial preventive implications, involving intensive screening and smoking cessation interventions or campaigns. Recent investigations show genetic association of several polymorphisms with lung cancer in a candidate gene based approach [Sobti et al, ; Parl, ; Sreeja et al, , Shah et al, ; Singh et al, ; Shukla et al, ; Singh and Behera, ; Phukan et al, ; Saikia et al, ; Shen et al, ; Sharma et al, ; Peddireddy et al, ]. A genome‐wide association study also revealed risk of lung cancer in never smokers, particularly women of East Asian origin and reported associations of several susceptibility loci, i.e., 10q25.2 (rs7086803, P = 3.54 × 10 ‐18 ), 6q22.2 (rs9387478, P = 4.14 × 10 ‐10 ) and 6p21.32 (rs2395185, P = 9.51 × 10 ‐9 ) [Lan et al, ] and with the malady.…”

“…a Forest plot for the odds ratios (ORs) of the SNP rs1048943 of CYP1A1 for the occurrence of lung cancer stratified by smoking status in sub-group analysis, b combined Forest plot, for the odds ratios (ORs) of the SNP rs1048943 of CYP1A1 for the occurrence of lung cancer stratified by smoking status in sub-group analysis between nonsmokers and smokers. [Sobti et al, 2003[Sobti et al, , 2004[Sobti et al, , 2008[Sobti et al, , 2009Parl, 2005;Sreeja et al, 2005, 2008a, Shah et al, 2008Singh et al, 2010Singh et al, , 2016Shukla et al, 2013;Singh and Behera, 2013;Phukan et al, 2014;Saikia et al, 2014;Shen et al, 2014;Sharma et al, 2015;Peddireddy et al, 2016]. A genome-wide association study also revealed risk of lung cancer in never smokers, particularly women of East Asian origin and reported associations of several susceptibility loci, i.e., 10q25.2 (rs7086803, P 5 3.54 3 10 -18 ), 6q22.2 (rs9387478, P 5 4.14 3 10 -10 ) and 6p21.32 (rs2395185, P 5 9.51 3 10 -9 ) [Lan et al, 2012] and with the malady.…”

“…Several genome-wide association studies (GWAS) have so far identified 16 susceptibility loci (P 5.00 3 10 -8 ) worldwide that are associated with lung cancer risk [Wang et al, 2008;Hu et al, 2011;Dong et al, 2012] and four loci out of them showed evidences of association of lung cancer risk in smokers [Dong et al, 2012]. However, most of these reports were based on Caucasian and Chinese populations, and many identified risk alleles have not been adequately evaluated in Indian population in spite of several case-control investigations on the Indian population from different geographical zones [Sobti et al, 2003[Sobti et al, , 2004[Sobti et al, , 2008[Sobti et al, , 2009Sreeja et al, 2005Sreeja et al, , 2008aSreeja et al, , 2008bSreeja et al, , 2008cJain et al, 2005;Pachouri et al, 2006Pachouri et al, , 2007Kotnis et al, 2008;Shah et al, 2008;Singh et al, 2010Singh et al, , 2016Tilak et al, 2011Tilak et al, , 2013Ihsan et al, 2011a,;Kant Shukla et al, 2013;Natukula et al, 2013;Shukla et al, 2013;Bag et al, 2014;Phukan et al, 2014;Saikia et al, 2014;Uppal et al, 2014;Sharma et al, 2015;Kumari et al, 2016;Peddireddy et al, 2016]. To date, researchers have not been able to delineate the overall effect of the genes and the genetic variations on lung cancer susceptibility in the populations of Indian origin, due to certain conflicting results.…”

Association of eNOS and ACE gene polymorphisms and plasma nitric oxide with risk of non‐small cell lung cancer in South India

“…Environmental, life style and epigenetic factors are known to contribute to the risk of NSCLC. Among the epigenetic factors, genetic polymorphisms are predicted to be one of the major contributing factors for the occurrence of NSCLC . Genetic polymorphisms in genes belonging to different classes and their association with the risk of NSCLC were described .…”

The Relation between Polymorphisms in Exon 5 and Exon 6 of GSTP1 Gene and the Risk of Lung Cancer in Iranian People

“…In the first phase, the antioxidant defense is performed by the cytochrome P450 (CYP) enzymes. Furthermore, the defense in the second phase is done by the glutathione S-transferase (GSTs) enzymes and through conjugation of PAHs with glutathione GSH, which is the first stage of the mercapturic acid synthesis reaction that can prevent the damage in macromolecules (Mota et al, 2015;Peddireddy et al, 2016). GSTs (EC 2.5.1.18) have been identified as a superfamily of dopaminergic enzymes, which combine endogenous products derived from oxidative stress and electrophilic xenobiotics such as carcinogens, pesticides, drugs and bio-contaminating materials targeted (Hayes et al, 2005).…”