The association of GSTM1 and GSTT1 deletion ...

Meta Gene 11 (2017) 111–116

Contents lists available at ScienceDirect

Meta Gene journal homepage: www.elsevier.com/locate/mgene

The association of GSTM1 and GSTT1 deletion polymorphisms with lung cancer risk: Evidence from an updated meta-analysis Saima Shakil Malik a,⁎, Nosheen Masood a, Mehreen Baig b, Azra Yasmin a a b

Microbiology and Biotechnology Research Lab, Fatima Jinnah Women University, The Mall, 46000 Rawalpindi, Pakistan Surgical Unit, Fauji Foundation Hospital, 46000 Rawalpindi, Pakistan

a r t i c l e

i n f o

Article history: Received 19 September 2016 Accepted 16 December 2016 Available online 19 December 2016 Keywords: GSTM1 GSTT1 Lung cancer Polymorphism Null deletion Lung carcinoma

a b s t r a c t Lung cancer is considered as most frequent malignancy all over the world. Glutathione S transferases are the active candidates for the susceptibility of lung cancer. Different studies have reported the association of GSTM1 and GSTT1 null deletion polymorphism with risk of lung cancer. But inconsistent results were reported. Therefore aim of the current study was to elucidate the role of GSTM1 and GSTT1 polymorphism in lung cancer development. PubMed, NCBI, EMBASE and Web of Science were comprehensively searched to explore the relationship of GSTM1 and GSTT1 with lung carcinoma in various populations in the era of last ten years. ORs with 95% CI were used to find the association between risk of lung carcinoma and GSTM1 and GSTT1 polymorphism. MedClac and STATA were used to analyze and interpret the results. The study comprise of 6491 lung carcinoma cases and 7807 normal healthy controls. The data showed that GSTM1 was strongly associated (OR = 1.31) with risk of lung cancer whereas no association was observed for GSTT1 (OR = 0.27) null deletion. The current study evinced that GSTM1 may contribute towards the development of lung cancer. Furthermore, properly designed studies with greater sample size are required to confirm validity the results. © 2016 Elsevier B.V. All rights reserved.

Contents 1. 2.

Introduction . . . . . . . . . . . . . . . Methodology . . . . . . . . . . . . . . . 2.1. Identification and eligibility of studies 2.2. Data extraction . . . . . . . . . . 2.3. Statistical analysis . . . . . . . . . 3. Results . . . . . . . . . . . . . . . . . 3.1. Test of heterogeneity . . . . . . . . 3.2. Quantitative data synthesis . . . . . 4. Discussion . . . . . . . . . . . . . . . . 5. Conclusion . . . . . . . . . . . . . . . . Ethical approval/informed consent . . . . . . . Conflict of interest . . . . . . . . . . . . . . . Financial assistance . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

111 112 112 112 113 113 113 113 113 114 114 114 114 115

1. Introduction

⁎ Corresponding author: Microbiology and Biotechnology Research Lab, Fatima Jinnah Women University, The Mall, Rawalpindi, Pakistan. E-mail address: [email protected] (S.S. Malik).

http://dx.doi.org/10.1016/j.mgene.2016.12.006 2214-5400/© 2016 Elsevier B.V. All rights reserved.

Worldwide lung cancer is most common and it is primary cause of death in males and secondary in females. Worldwide 1.6 million cases are registered for lung cancer and death figure has reached to 1.4 million each year. Most (90%) of the lung cancers are of non-small cell type of lung cancer. It was confirmed from the epidemiological studies that

112

S.S. Malik et al. / Meta Gene 11 (2017) 111–116

smoking and environmental exposure to asbestos plays fundamental role in the development of lung carcinoma. However, only a small number of individuals will becomes the victim of lung cancer, who are exposed to these potential risk factors. It shows that an individual's susceptibility play a definite role in the onset and development of lung carcinogenesis. Some other factors are also involved in the etiology of lung carcinoma including ultra-violent radiations, viruses and occupation (Rebecca et al., 2013). Lung carcinoma is a multistage and multicellular process. It involves various genetic changes in the oncogenes suggesting an important role of genetic factors in the development of lung cancer. Glutathione Stransferases (GSTs) is a superfamily comprising of phase II metabolic enzymes involve in the catalysis of glutathione, carcinogens, chemotherapeutic drugs, environmental pollutants, and many other xenobiotics (Conaway et al., 2002). These enzymes helps in the activation of a conjugation between carcinogens to glutathione (water soluble), and promotes its removal from the cell (Hayes and Pulford, 1995; Abdollahi et al., 2004). Glutathione S transferases mu 1 (GSTM1) and glutathione S transferases theta 1 (GSTT1) null deletion polymorphisms lead to complete loss of enzymatic activity. Hence, people having GSTs null deletion may have reduced ITCs (isothiocyanates) metabolism (Coles et al., 2002). The detailed literature review represents that GSTM1 and GSTT1 null deletion varies ethnically and geographically (Senthilkumar and Thirumurugan, 2012). Although deletion polymorphisms of GSTM1 and GSTT1 genes in lung carcinoma have been reported since many years but contrasting results were illustrated. No conclusion can be reached either these genetic deletions are a risk factor for lung cancer development or not. The current study has been designed with an aim to reveal the exact pattern of these genetic deletions according to different geographical locations in lung cancer.

2. Methodology 2.1. Identification and eligibility of studies We searched the NCBI, EMBASE, PUBMED and Web of science databases in order to investigate the association of GSTM1 and GSTT1 gene polymorphisms with the risk of lung cancer. Different keywords like GSTM1, GSTT1, lung cancer or non-small cell lung cancer or lung tumor, glutathione S transferases, polymorphisms and genetic variations were used. The reference list of a number of review articles and other relevant researches were scanned to find out maximum eligible studies. Eligibility criteria includes: (a) Only full text published research articles with case-control studies were included (b) All the articles included in this review were in English language (c) Studies focusing only on polymorphisms of GSTM1 and GSTT1 with lung cancer were considered (d) Odds ratio (OR) and confidence interval (95% CI) of the selected studies were used to statistically evaluate the associations. Exclusion criteria includes: (a) editorials and review articles (b) Studies that used GSTM1 and GSTT1 gene polymorphisms to observe survival, severity, progression and response to treatment with lung cancer (c) Family based studies were also excluded in this review. Study scheme is illustrated in the form of a flow diagram shown in Fig. 1. 2.2. Data extraction Two researchers independently extracted data and resolved the disagreements through consensus. Author, publication year, design of study, geographical location (country), number of cases and controls together with deletion of GSTM1 and GSTT1 were extracted from selected studies. Different ethnic decants were categorized as Asians, Europeans, Americans and Africans. All the information was extracted from already

Fig. 1. Flow diagram of literature search.


113

Table 1 Characteristics of studies included in review. Country

Cases

Controls

GSTM1 = OR (CI) P value

GSTT1 = OR (CI) P value

Reference

Mexico Belarus Bangladesh India Inner Mongolia (China) Han population (China) China China India Austrias China China Tunisia Turkey China Brazil China Turkey New York Thailand California Turkey Korea Thailand USA India China China Germany Hong Kong

190 115 106 154 142 180 523 110 218 789 360 217 101 213 200 64 150 75 143 91 311 154 318 211 166 146 217 152 446 229

382 328 116 154 190 260 523 100 238 789 360 198 101 231 200 87 150 55 447 82 622 102 353 201 181 146 200 152 662 197

0.98 (0.62–1.53) 0.93 1.17 (0.76–1.80) 1.06 (0.63–1.81) 0.93 0.60 (0.32–1.14), 0.12 2.29 (1.46–3.57) 0.00 1.88 (1.28–2.76) 0.001 1.87 (1.46–2.39) b 0.01 2.07 (1.19–3.59) 0.009 1.03 (0.71–1.51) 0.875 0.95 (0.76–1.19) 1.59 (1.17, 2.17) 0.003 1.56 (1.06–2.30) 0.02 0.78 (0.37–1.62) 0.51 1.15 (0.77–1.72) 0.49 2.75 (1.47–5.16) 1.23 (0.63–2.38) 0.64 1.13 (0.57–2.24) N0.05 1.57 (0.32–7.54) 0.57 1.80 (0.81–4.02) 0.13 1.87 (0.89–3.9) 0.09 0.52(0.31–0.86) 0.16 1.39 (0.70–1.90) 0.57 0.63 0.8 (0.5–1.2) 1.11 (0.70–1.78) 0.89 1.2 (0.76–2.09) 0.36 0.02

1.51 (0.87–2.62) 0.13 2.40 (1.45–4.00) 0.81 (0.44–1.47) 0.57 0.35 (0.17–0.73), 0.005 0.95 (0.61–1.48) 0.84 1.12 (0.76–1.64) 0.55 1.57 (1.23–2.0) b 0.01 1.900 (1.084–3.331) 0.024 1.87(1.25–2.80) 0.002 0.85 (0.64–1.12)

Perez-Morales et al., 2014 Mikhalenko et al., 2014 Nasir Uddin et al., 2014 Ihsan et al., 2014 Jiang et al., 2014 Jiang et al., 2014 Pan et al., 2014 Zhang et al., 2014 Shukla et al., 2013 Lopez-Cima et al., 2012 Liu et al., 2012 Li et al., 2012 Fatma et al., 2012 Ada et al., 2012 Chen et al., 2012 Cabral et al., 2010 Jin et al., 2010 Altinisik et al., 2010 Lam et al., 2009 Klinchid et al., 2009 Carpenter et al., 2009 Demir et al., 2007 Yang et al., 2007 Pisani et al., 2006 Wenzlaff et al., 2005 Sreeja et al., 2005 Li et al., 2004 Liang et al., 2004 Schneider et al., 2004 Chan-Yeung et al., 2004

2.3. Statistical analysis The strength of the relationship between GSTM1 and GSTT1 deletion polymorphism and risk of lung cancer was evaluated by OR with 95% CI. Heterogeneity was measured by using Cochrane Q test. Both random effects model and fixed effects model were used to estimate the values of OR. When no heterogeneity fixed effects model was used (DerSimonian and Laird, 1986). Statistical analysis was done by using MedCalc and STATA13.0 software. Result with a P b 0.05 was contemplated as statistically significant.

0.76 (0.39–1.47) 0.52 0.87 (0.18–4.10) 0.86 1.06 (0.58–1.95) 0.83 0.69 (0.34–1.39) 0.29

0.19 0.74 (0.41–1.33) 0.52 2.87 (1.43–5.73) 0.003 2.06 (1.30–3.24) 0.88 (0.59–1.32) 1.69 (1.12–2.56)

1.34 (0.99–1.81)

published articles and individual authors were not contacted for any information.

0.83 (0.47–1.45) 0.51 1.15 (0.71–1.88) 0.56

and GSTT1 null deletion polymorphism with the risk of lung cancer development. Overall 28 studies represented the association between GSTM1 and lung carcinoma while 22 case reports were included to analyze the relationship of lung cancer risk and GSTT1 polymorphism. 3.1. Test of heterogeneity The heterogeneity of GSTM1 and GSTT1 polymorphism was analyzed for 28 and 22 selected case control studies respectively. The results depicted that GSTM1 and GSTT1 polymorphisms had no heterogeneity (P ≥ 0.05) with lung carcinoma. Therefore, fixed-effects model was used to calculate summary odds ratios for both of the genes deletion polymorphism. 3.2. Quantitative data synthesis

3. Results A database was constructed from the information extracted in the light of inclusion and exclusion criteria from available articles in the past 10 years. Some necessary data was arranged in Table 1, which includes country (area), number of cases and controls, Odds ratio, confidence interval and P value of association of GSTM1 and GSTT1 deletion with lung cancer risk and year as well. There were a total of 30 studies with 6491 cases and 7807 controls regarding the GSTM1

Table 2 Odds ratios summary on the relation of GSTM1 and GSTT1 deletion polymorphism to risk of lung carcinoma. Polymorphism Cases/controls Heterogeneity Summary test OR (95% CI) GSTM1

6110/7458

(P ≥ 0.05)

GSTT1

4671/5774

(P ≥ 0.05)

1.31 (1.29–1.33) 0.27 (0.23–0.32)

Hypothesis test Z

P

41.4

P b 0.001

−188 P N 0.05

Total number of controls and cases for evaluating the association of GSTM1 and GSTT1 with lung carcinoma risk from the selected studies are given in Table 2. The summary odds ratios of GSTM1 and GSTT1 polymorphism linked to lung carcinoma based on case control studies were listed in Table 2. We observed that GSTM1 deletion was associated (OR = 1.31; CI = 1.29–1.33) with the increase risk of lung cancer (Fig. 2) whereas no association was observed regarding the deletion polymorphism of GSTT1 and lung carcinoma (OR = 0.27; CI = 0.23– 0.32) as illustrated in Fig. 3. 4. Discussion GSTM1 and GSTT1 genes have null deletion polymorphism, as a result complete enzymatic activity was lost. Hence, individuals with homozygous deletion polymorphism of these genes are at greater risk towards the development of malignancies (Malik et al., 2016). Various genetic studies have reported some valuable knowledge regarding the association of GSTM1 and GSTT1 polymorphism with risk of cancer susceptibility. Some studies illustrated very high frequencies of GSTM1 and GSTT1 deletion among cancer patients while contrasting results were

114


Fig. 2. Forest plot of odds ratio (OR) for GSTM1 deletion polymorphism associated with risk of lung cancer. The squares and horizontal lines corresponds to study specific OR.

also available (Nasir Uddin et al., 2014; Jiang et al., 2014; Zhang et al., 2014). Another important point is that GSTM1 and GSTT1 genes may be involved in the etiology of more than one cancer types (Masood et al., 2010; Berber et al., 2013; Pan et al., 2014; Malik et al., 2015). Some of the meta-analysis reported the association of GSTM1 and GSTT1 null deletion polymorphism with different cancers in various populations (Wang et al., 2012; Peng et al., 2014), but inconsistency was observed in them. Therefore in this review, we performed brief and systematic literature search to exclusively evaluate the association of GSTM1 and GSTT1 with risk of lung carcinoma in different populations. From the present study, comprising of 6491 lung cancer cases and 7807 controls from 30 case-control studies it was found that GSTM1 deletion may be associated (OR = 1.31, CI 1.29–1.33) with the risk of lung cancer development. However no association was observed regarding the deletion polymorphism of GSTT1 with lung cancer risk. Different meta-analysis have reported GSTM1 and its association with lung carcinoma but have some important limitations. For example, some of the overlapping studies were not accurately excluded. Various published research articles were also missing in them (Liang et al., 2004; Chan-Yeung et al., 2004; Shi et al., 2008). Our study had certain advantages. It comprises of a huge number of case control studies to justify the results in various populations. Both fixed effects model and random effects model were used to evaluate the OR and CI. No heterogeneity was observed in this review which is another proof to confirm the accuracy of results. Some possible limitations include the lack of original data in the studies eligible for review it results in a serious limitation for the evaluation of gene-environment and gene-gene interactions in the development of

lung cancer. Only published studies were included in this review, therefore there may be some chances of publication bias, even it was not represented by the statistical analysis.

5. Conclusion This comprehensive meta-analysis depicts that GSTM1 null deletion may be a risk factor in lung cancer development but GSTT1 does not plays any role in it. In the future, large scale studies should be taken into consideration in order to verify the results.

Ethical approval/informed consent As this is a review article and all the data was collected from published studies so, no ethical approval/informed consent is required.

Conflict of interest The authors have declared that no conflict of interest exists.

Financial assistance This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.


115

Fig. 3. Forest plot of odds ratio (OR) for GSTT1 deletion polymorphism associated with risk of lung cancer. The squares and horizontal lines corresponds to study specific OR.

References Abdollahi, M., Ranjbar, A., Shadnia, S., Nikfar, S., Rezaie, A., 2004. Pesticides and oxidative stress: a review. Med. Sci. Monit. 10, 141–147. Ada, A.O., Kunak, S.C., Hancer, F., Soydas, E., Alpar, S., Gulhan, M., Iscan, M., 2012. Association between GSTM1, GSTT1, and GSTP1 polymorphisms and lung cancer risk in a Turkish population. Mol. Biol. Rep. 39 (5), 5985–5993. Altinisik, J., Balta, Z.B., Aydin, G., Ulutin, T., Buyru, N., 2010. Investigation of glutathione Stransferase M1 and T1 deletions in lung cancer. Mol. Biol. Rep. 37 (1), 263–267. Berber, U., Yilmaz, I., Yilmaz, O., Haholu, A., Kucukodaci, Z., Ates, F., Demirel, D., 2013. CYP1A1 (Ile462 Val), CYP1B1 (Ala 119 Ser and Val 432 Leu), GSTM1 (null), and GSTT1 (null) polymorphisms and bladder cancer risk in a Turkish population. Asian Pac. J. Cancer Prev. 14 (6), 3925–3929. Cabral, R.E., Caldeira-de-Araujo, A., Cabral-Neto, J.B., Costa CarvalhoMda, G., 2010. Analysis of GSTM1 and GSTT1 polymorphisms in circulating plasma DNA of lung cancer patients. Mol. Cell. Biochem. 338 (1–2), 263–269. Carpenter, L., Yu, M.C., London, S.J., 2009. Dietary isothiocyanates, glutathione S-transferase M1 (GSTM1), and Lung Cancer Risk in African Americans and Caucasians from Los Angeles County, California. Nutr. Cancer 61 (4), 492–499. Chan-Yeung, M., Tan-Un, K.C., Ip, M.S., Tsang, K.W., Ho, S.P., Ho, J.C., Chan, H., Lam, W.K., 2004. Lung cancer susceptibility and polymorphisms of glutathione-S-transferase genes in Hong Kong. Lung Cancer 45, 155–160. Chen, C.M., Jin, Y.T., Xu, H.Y., Zhang, C.Y., Zhang, H., Zhang, W.M., et al., 2012. Effects of CYP1A1 and GSTM1 gene polymorphisms and BPDE-DNA adducts on lung cancer. Zhonghua, Y., Xue, Y., Chuan, X., Za, Z. 29, 23–27. Coles, B.F., Chen, G., Kadlubar, F.F., Radominska-Pandya, A., 2002. Interindividual variation and organ-specific patterns of glutathione S-transferase alpha, mu, and pi expression in gastrointestinal tract mucosa of normal individuals. Arch. Biochem. Biophys. 403, 270–276. Conaway, C.C., Yang, Y.M., Chung, F.L., 2002. Isothiocyanates as cancer chemopreventive agents: their biological activities and metabolism in rodents and humans. Curr. Drug Metab. 3, 233–255. Demir, A., Altin, S., Pehlivan, D., Demir, M., Yakar, F., Seyhan, E.C., Dincer, S.E., 2007. The role of GSTM1 gene polymorphisms in lung cancer development in Turkish population. J. Carcinog. 6, 13. DerSimonian, R., Laird, N., 1986. Meta-analysis in clinical trials. Control. Clin. Trials 7, 177–188.

Fatma, B., Aida, T., Maurice, J.A., Saguem, S., 2012. Glutathione S-transferase M1 and T1, CYP1A2-2467T/delT polymorphisms and non small-cell lung cancer risk in Tunisian sample. Egypt. J. Med. Hum. Genet. 13, 307–312. Hayes, J.D., Pulford, D.J., 1995. The glutathione S-transferase gene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance. Crit. Rev. Biochem. Mol. Biol. 30, 445–600. Ihsan, R., Chauhan, S.P., Mishra, K.A., Singh, L.C., Sharma, D.J., Zomawia, E., et al., 2014. Copy number polymorphism of glutathione-S-transferase genes (GSTM1 & GSTT1) in susceptibility to lung cancer in a high-risk population from north-east India. Indian J. Med. Res. 139, 720–729. Jiang, X.Y., Chang, F.H., Bai, T.Y., Lv, X.L., Wang, M.J., 2014. Susceptibility of lung cancer with polymorphisms of CYP1A1, GSTM1, GSTM3, GSTT1 and GSTP1 genotypes in the population of Inner Mongolia region. Asian Pac. J. Cancer Prev. 15, 5207–5214. Jin, Y., Xu, H., Zhang, C., Kong, Y., Hou, Y., Xu, Y., Xue, S., 2010. Combined effects of cigarette smoking, gene polymorphisms and methylations of tumor suppressor genes on non small cell lung cancer: a hospital-based case-control study in China. BMC Cancer 10, 422. Klinchid, J., Chewaskulyoung, B., Saeteng, S., Lertprasertsuke, N., Kasinrerk, W., Cressey, R., 2009. Effect of combined genetic polymorphisms on lung cancer risk in northern Thai women. Cancer Genet. Cytogenet. 195, 143–149. Lam, T.K., Ruczinski, I., Helzlsouer, K., Shugart, Y.Y., Li, K.E., Clipp, S., Strickland, P.T., Alberg, A.J., 2009. Copy number variants of GSTM1 and GSTT1 in relation to lung cancer risk in a prospective cohort study. Ann. Epidemiol. 19 (8), 546–552. Li, W.Y., Lai, B.T., Zhan, X.P., 2004. The relationship between genetic polymorphism of metabolizing enzymes and the genetic susceptibility to lung cancer. Zhonghua, L., Xing, B., Xue, Z.Z. 25, 1042–1045. Li, W., Yue, W., Zhang, L., Zhao, X., Ma, L., Yang, X., Zhang, C., Wang, Y., Gu, M., 2012. Polymorphisms in GSTM1, CYP1A1, CYP2E1, and CYP2D6 are associated with susceptibility and chemotherapy response in non-small-cell lung cancer patients. Lung 190, 91–98. Liang, G.Y., Pu, Y.P., Yin, L.H., 2004. Studies of the genes related to lung cancer susceptibility in Nanjing Han population, China. Yi, C. 26, 584–588. Liu, D., Wang, F., Wang, Q., Guo, X., Xu, H., Wang, W., Zhang, L., 2012. Association of glutathione S-transferase M1 polymorphisms and lung cancer risk in a Chinese population. Clin. Chim. Acta 414, 188–190. Lopez-Cima, M.F., Alvarez-Avellon, S.M., Pascual, T., Fernandez-Somoano, A., Tardon, A., 2012. Genetic polymorphisms in CYP1A1, GSTM1, GSTP1 and GSTT1 metabolic genes and risk of lung cancer in Asturias. BMC Cancer 12, 433.

116


Malik, S.S., Masood, N., Yasmin, A., 2015. Prostate cancer and glutathione S-transferase deletions. EXCLI J. 14, 1049–1054. Malik, S.S., Nawaz, G., Masood, N., 2016. Genotypes of GSTM1 and GSTT1: Useful determinants for clinical outcome of bladder cancer in Pakistani population. Egypt. J. Hum. Med. Genet. http://dx.doi.org/10.1016/j.ejmhg.2016.03.001. Masood, N., Ishrat, M., Malik, F.A., Baig, R.M., Kayani, M.A., 2010. Association of GSTM1 and GSTT1 gene deletions with risk of head and neck cancer in Pakistan: a case control study. Asian Pac. J. Cancer Prev. 11, 881–885. Mikhalenko, A.P., Krupnova, E.V., Chakova, N.N., Chebotareva, N.V., Demidchik, Y.E., 2014. Evaluation of connection of combinations of polymorphic variants of genes of xenobiotic metabolizing enzymes with a predisposition to lung cancer. Tsitol. Genet. 48 (2), 52–59. Nasir Uddin, M.M., Ahmed, U.M., Islam, S.M., Islam, S.M., Sayeed, B.S.M., Kabir, Y., Hasnat, A., 2014. Genetic polymorphisms of GSTM1, GSTP1 and GSTT1 genes and lung cancer susceptibility in the Bangladeshi population. Asian Pac. J. Trop. Biomed. 4 (12), 982–989. Pan, C., Zhu, G., Yan, Z., Zhoua, Y., Liu, Z., 2014. Glutathione S-Transferase T1 and M1 polymorphisms are associated with lung cancer risk in a gender-specific manner. Oncol. Res. Treat. 37, 164–169. Peng, J., Liu, H.Z., Zhu, Y.J., 2014. Null glutathione S-transferase T1 and M1 genotypes and oral cancer susceptibility in China and India—a meta-analysis. Asian Pac. J. Cancer Prev. 15, 287–290. Perez-Morales, R., Mendez-Ramirez, I., Moreno-Macias, H., Mendoza-Posadas, A.D., Martinez-Ramirez, O.C., Castro-Hernandez, C., Gonsebatt, M.E., Rubio, J., 2014. Genetic susceptibility to lung cancer based on candidate genes in a sample from the Mexican Mestizo population: a case-control study. Lung 192 (1), 167–173. Pisani, P., Srivatanakul, P., Randerson-Moor, J., Vipasrinimit, S., Lalitwongsa, S., Unpunyo, P., Bashir, S., Bishop, D.T., 2006. GSTM1 and CYP1A1 polymorphisms, tobacco, air pollution, and lung cancer: a study in rural Thailand. Cancer Epidemiol. Biomark. Prev. 15 (4), 667–674.

Rebecca, S., Naishadham, D., Jemal, A., 2013. Cancer statistics, 2013. CA Cancer J. Clin. 63, 11–30. Schneider, J., Bernges, U., Philipp, M., Woitowitz, H.J., 2004. GSTM1, GSTT1, and GSTP1 polymorphism and lung cancer risk in relation to tobacco smoking. Cancer Lett. 208, 65–74. Senthilkumar, K.P., Thirumurugan, R., 2012. GSTM1 and GSTT1 allele frequencies among various Indian and non-Indian ethnic groups. Asian Pac. J. Cancer Prev. 13 (12), 6263–6267. Shi, X., Zhou, S., Wang, Z., Zhou, Z., 2008. CYP1A1 and GSTM1 polymorphisms and lung cancer risk in Chinese populations: a meta-analysis. Lung Cancer 59, 155–163. Shukla, R.K., Tilak, A.R., Kumar, C., Kant, S., Kumar, A., Mittal, B., Bhattachary, S., 2013. Associations of CYP1A1, GSTM1 and GSTT1 polymorphisms with lung cancer susceptibility in a Northern Indian population. Asian Pac. J. Cancer Prev. 14, 3345–3349. Sreeja, L., Syamala, V., Hariharan, S., Madhavan, J., Devan, S.C., Ankathil, R., 2005. Possible risk modification by CYP1A1, GSTM1 and GSTT1 gene polymorphisms in lung cancer susceptibility in a South Indian population. J. Hum. Genet. 50, 618–627. Wang, D., Zhang, L.M., Zhai, J.X., Liu, D.W., 2012. GSTM1 and GSTT1 polymorphisms and colorectal cancer risk in Chinese population: a meta-analysis. Int. J. Color. Dis. 27, 901–909. Wenzlaff, A.S., Cote, M.L., Bock, C.H., Land, S.J., Schwartz, A.G., 2005. GSTM1, GSTT1 and GSTP1 polymorphisms, environmental tobacco smoke exposure and risk of lung cancer among never smokers: a population-based study. Carcinogenesis 26 (2), 395–401. Yang, M., Choi, Y., Hwangbo, B., Lee, S.J., 2007. Combined effects of genetic polymorphisms in six selected genes on lung cancer susceptibility. Lung Cancer 57 (2), 135–142. Zhang, H., Wu, X., Xiao, Y., Chen, M., Li, Z., Wei, X., Tang, K., 2014. Genetic polymorphisms of glutathione S-transferase M1 and T1, and evaluation of oxidative stress in patients with non-small cell lung cancer. Eur. J. Med. Res. 19, 67–72.