Genetic Polymorphism of GSTM1 and GSTT1 and Risk of Prostatic Carcinoma - a Meta-analysis of 7,281 Prostate Cancer Cases and 9,082 Healthy Controls

  • Malik, Saima Shakil (Environmental Sciences (Biotechnology), Fatima Jinnah Women University The Mall) ;
  • Kazmi, Zehra (Environmental Sciences (Biotechnology), Fatima Jinnah Women University The Mall) ;
  • Fatima, Iffat (Quaid E Azam University) ;
  • Shabbir, Riffat (Environmental Sciences (Biotechnology), Fatima Jinnah Women University The Mall) ;
  • Perveen, Shagufta (Environmental Sciences (Biotechnology), Fatima Jinnah Women University The Mall) ;
  • Masood, Nosheen (Environmental Sciences (Biotechnology), Fatima Jinnah Women University The Mall)
  • Published : 2016.05.01


Genetic polymorphisms constitute one of the reasons behind the racial variation in prostate cancer occurrence. Published studies regarding genetic associations of glutathione S-transferase mu 1 (GSTM1) and glutathione S-transferase theta 1 (GSTT1) null deletion polymorphisms with prostatic carcinoma have generated inconsistent results among different populations. To date, even a single meta-analysis is not available representing the association of these genes with prostate cancer in different ethnic groups. Therefore, the aim of the current study was to provide a clear picture of GSTM1 and GSTT1 null deletion and risk of prostate cancer among different ethnic groups (i.e. Asians, Europeans, Americans, Africans and Eurasians). A systematic search was performed with the help of various search engines to find out the all the recent studies (2004 to 2015) evaluating the role of GSTM1 and GSTT1 deletion in prostate cancer development. Odds ratios (ORs) with 95% confidence interval (CI) of a total of 34 studies with 7,281 cases and 9,082 controls was analyzed using STATA and MedCalc software. Overall, GSTM1 deletion (OR 3.67; CI 1.39-9.85; P= 0.001) was strongly associated with prostatic cancer. In the sub group analysis GSTM1 null deletion was also significantly associated with prostate cancer among Asians (OR 4.84; CI 1.08-21.5; P= 0.03), Eurasians (OR 17.69; CI 9.87-31.70; P< 0.001) and Americans (OR 0.11; CI 0.01-1.06; P= 0.05). No association was observed among Europeans (P=0.42) and Africans (P= 0.40). As a whole GSTT1 null deletion (OR 0.85; CI 0.28-2.58; P= 0.77) did not show anyt significant association with prostate cancer risk among different populations. When the data were stratified into different groups, however, Africans demonstrated a significant association of GSTT1 null deletion (OR 1.95; CI 1.57-2.39; P<0.001) with prostate cancer, whereas no association was found among Asians (P= 0.90), Americans (P= 0.50), Europeans (P= 0.89) and Eurasians (P= 1.0). In conclusion, both GSTM1 and GSTT1 may contribute to prostate cancer development but GSTM1 may prove to be a stronger candidate risk factor.


  1. Agalliu I, Lin DW, Salinas CA, et al (2006). Polymorphisms in the glutathione S-transferase M1, T1, and P1 genes and prostate cancer prognosis. Prostate, 66, 1535-41.
  2. Aktas D, Hascicek M, Sozen S, et al (2004). CYP1A1 and GSTM1 polymorphic genotypes in patients with prostate cancer in a Turkish population. Cancer Genet Cytogenet, 154, 81-85.
  3. Ali M, Ibrahim AT, Ibrahim MT, et al (2015). Deletion Polymorphism of Glutathione S-transferases M1 and T1 genes in the Sudanese Population. Am J Med Studies, 3, 8-12.
  4. Amankwah EK, Sellers TA, Park JY. (2012). Gene variants in the angiogenesis pathway and prostate cancer. Carcinogenesis, 33, 1259-69.
  5. Ansari SB, Vasudevan R, Bakhshi A, et al (2010). Analysis of glutathione S-transferase (M1, T1 and P1) gene polymorphisms in Iranian prostate cancer subjects. Afr J Biotechnol, 9, 7230-35.
  6. Ashtiani ZO, Hasheminasab SM, Ayati M, Goulian BS, Modarressi MH. (2011). Are GSTM1, GSTT1 and CAG repeat length of androgen receptor gene polymorphisms associated with risk of prostate cancer in Iranian patients? Pathol Oncol Res, 17, 269-5.
  7. Caceres DD, Iturrieta J, Acevedo C, et al (2005). Relationship among metabolizing genes, smoking and alcohol used as modifier factors on prostate cancer risk: Exploring some gene-gene and gene-environment interactions. Eur J Epidemiol, 20, 79-88.
  8. Cao DL, Ye DW, Dai B, et al (2015). Association of glutathione S-transferase T1 and M1 polymorphisms with prostate cancer susceptibility in populations of Asian descent: a meta-analysis. Oncotarget, 6, 35843-50.
  9. Cao DL, Ye DW, Zhang HL, et al (2011). A multiplex model of combining gene-based, proteinbased, and metabolite-based with positive and negative markers in urine for the early diagnosis of prostate cancer. Prostate, 71, 700-10.
  10. Catsburg C, Joshi AD, Corral R, et al (2012). Polymorphisms in carcinogen metabolism enzymes, fish intake, and risk of prostate cancer. Carcinogenesis, 33, 1352-9.
  11. Crawford ED, Higano CS, Shore ND, et al (2015). Treating patients with metastatic castration resistant prostate cancer: A Comprehensive Rev Available Therapies. J Urol, 194, 1537-47.
  12. DerSimonian R, Laird N, (1986). Meta-analysis in clinical trials. Control Clin Trials, 7, 177-88.
  13. Detchokul S and Frauman AG, (2011). Recent developments in prostate cancer biomarker research: therapeutic implications. Br J Clin Pharmacol, 71, 157-74.
  14. Economopoulos KP, Sergentanis TN, Vlahos NF, (2010). Glutathione Stransferase M1, T1, and P1 polymorphisms and ovarian cancer risk: a meta-analysis. Int J Gynecol Cancer, 20, 732-37.
  15. Foley R, Hollywood D, Lawler M, (2004). Molecular pathology of prostate cancer: the key to identifying new biomarkers of disease. Endocr Relat Cancer, 11, 477-88.
  16. Guan TY, Li M, Na YQ, (2005). Polymorphism of metabolic gene and genetic susceptibility to prostate cancer. Chin J Surg, 43, 1467-70.
  17. Hemelrijck MV, Rohrmann S, Steinbrecher A, et al (2012). Heterocyclic Aromatic Amine [HCA] Intake and Prostate Cancer Risk: Effect Modification by Genetic Variants. Nutr Cancer, 645, 704-43.
  18. Hu ZH, Lin YW, Chen H, et al (2013). Genetic polymorphisms of glutathione S- transferase M1 and prostate cancer risk in Asians: a metaanalysis of 18 studies. Asian Pac J Cancer Prev, 14, 393-98.
  19. Huang W, Shi H, Mo Z, et al (2015). GSTM1 and GSTT1 polymorphisms contribute to renal cell carcinoma risk: evidence from an updated meta-analysis. Scientific Reports, 5.
  20. Joseph MA, Moysich KB, Freudenheim JL, et al (2004). Cruciferous vegetables, genetic polymorphisms in glutathione Stransferases M1 and T1, and prostate cancer risk. Nutr Cancer, 50, 206-13.
  21. Komiya Y, Tsukino H, Nakao H, et al (2005). Human glutathione S-transferase A1, T1, M1, and P1 polymorphisms and susceptibility to prostate cancer in the Japanese population. J Cancer Res Clin Oncol, 131, 238-42.
  22. Kumar V, Yadav CS, Datta SK, et al (2011). Association of GSTM1 and GSTT1 polymorphism with lipid peroxidation in benign prostate hyperplasia and prostate cancer: a pilot study. Dis Markers, 30, 163-69.
  23. Kwon DD, Lee JW, Han DY, et al (2011). Relationship between the glutathione-S-transferase P1, M1, and T1 genotypes and prostate cancer risk in Korean subjects. Korean J Urol, 52, 247-52.
  24. Lai MT, Chen RH, Tsai FJ, et al (2005). Glutathione S-transferase M1 gene but not insulin-like growth factor-2 gene or epidermal growth factor gene is associated with prostate cancer. Urol Oncol, 23, 225-29.
  25. Latil AG, Azzouzi R, Cancel GS, et al (2011). Prostate carcinoma risk and allelic variants of genes involved in androgen biosynthesis and metabolism pathways. Cancer-Am Cancer Soc, 92, 1130-37.
  26. Lavender NA, Benford ML, VanCleave TT, et al (2009). Examination of polymorphic glutathione S-transferase (GST) genes, tobacco smoking and prostate cancer risk among men of African descent: a case-control study. BMC Cancer, 9, 397-7.
  27. Li M, Guan T, Li Y, et al (2008). Polymorphisms of GSTM1 and CYP1A1 genes and their genetic susceptibility to prostate cancer in Chinese men. Chin Med J, 121, 305-8.
  28. Lima MMJ, Oliveira MN, Granja F, et al (2008). Lack of association of GSTT1, GSTM1, GSTO1, GSTP1 and CYP1A1 polymorphisms for susceptibility and outcome in Brazilian prostate cancer patients. Folia Biol (Praha), 54, 102-8.
  29. Liu D, Liu Y, Ran L, et al (2013). GSTT1 and GSTM1 polymorphisms and prostate cancer risk in Asians: a systematic review and meta-analysis. Tumor Biol, 34, 2539-44.
  30. Liu D, Wang F, Wang Q, et al (2012). Association of glutathione S-transferase M1 polymorphisms and lung cancer risk in a Chinese population. Clin Chim Acta, 414, 188-90.
  31. Malik SS, Masood N, Yasmin A. (2015). Prostate cancer and glutathione s-transferase deletions. EXCLI J, 14, 1049-54.
  32. Mallick S, Romana M, Blanchet P, et al (2007). GSTM1 and GSTT1 polymorphisms and the risk of prostate cancer in a Caribbean population of African descent. Urol, 69, 1165-69.
  33. Masood N, Malik FA, Kayani MA, (2011). Expression of xenobiotic metabolizing genes in head and neck cancer tissues. Asian Pac J Cancer Prev, 12, 377-82.
  34. Masood N, Malik SS, (2014). Association of prostate and bladder cancers with genetic deletions of GSTs. J Rashid Latif Medical College, 2, 1-7.
  35. Masood N, Yasmin A, Kayani MA, (2013). Genetic deletions of GSTM1 and GSTT1 in head and neck cancer: review of the literature from 2000 to 2012. Asian Pac J Cancer Prev, 14, 3535-39.
  36. Medeiros R, Vasconcelos A, Costa S, et al (2004). Metabolic susceptibility genes and prostate cancer risk in a southern European population: the role of glutathione S-transferases GSTM1, GSTM3, and GSTT1 genetic polymorphisms. Prostate, 58, 414-20.
  37. Mittal RD, Mishra DK, Mandhani A, (2006). Evaluating polymorphic status of glutathione-S-transferase genes in blood and tissue samples of prostate cancer patients. Asian Pac J Cancer Prev, 7, 444-46.
  38. Mittal RD, Srivastava DS, Mandhani A, et al (2004). Polymorphism of GSTM1 and GSTT1 genes in prostate cancer: a study from North India. Indian J Cancer, 41, 115-19.
  39. Nock NL, Liu X, Cicek MS, et al (2006). Polymorphisms in polycyclic aromatic hydrocarbon metabolism and conjugation genes, interactions with smoking and prostate cancer risk. Cancer Epidemiol Biomarkers Prev, 15, 756-61.
  40. Nock NL, Tang D, Rundle A, et al (2007). Associations between smoking, polymorphisms in polycyclic aromatic hydrocarbon (pah) metabolism and conjugation genes and PAH-DNA adducts in prostate tumors differ by race cancer. Epidemiol Biomarkers Prev, 16, 1236-45.
  41. Oakley A, (2011). Glutathione transferases: a structural perspective. Drug Metab Rev, 43, 138-51.
  42. Pan DL, Samavedi S, Eldefrawy A, et al (2012). The current status of active surveillance for prostate cancer. Postgrad Med, 124, 50-58.
  43. Pan JZ, Huang JW, Zou HZ, et al (2012). The GSTT1 Null Genotype Contributes to Increased Risk of Prostate Cancer in Asians: a Meta-analysis. Asian Pac J Cancer Prev, 13, 2635-38.
  44. Rebecca S, Naishadham D, Ahmedin Jemal A (2013). Cancer Statistics, 2013. Ca Cancer J Clin, 63, 11-30.
  45. Safarinejad MR, Shafiei N, Safarinejad SH, (2011). Glutathione S-transferase gene polymorphisms (GSTM1, GSTT1, GSTP1) and prostate cancer: a case control study in Tehran, Iran. Prostate Cancer Prostatic Dis, 4, 105-13.
  46. Shukla RK, Tilak AR, Kumar C, et al (2013). Associations of CYP1A1, GSTM1 and GSTT1 polymorphisms with lung cancer susceptibility in a Northern Indian population. Asian Pac J Cancer Prev, 14, 3345-49.
  47. Siegel LR, Miller, DK. Jemal A. (2015). Cancer Statistics, 2015. Ca Cancer J Clin, 65, 5-9.
  48. Silig Y, Pinarbasi H, Gunes S, et al (2006). Polymorphisms of CYP1A1, GSTM1, GSTT1, and prostate cancer risk in Turkish population. Cancer Invest, 24, 41-45.
  49. Sivonova M, Waczulikova I, Dobrota D (2009). Polymorphisms of glutathione-S transferase M1, T1, P1 and the risk of prostate cancer: a case-control study. J Exp Clin Cancer Res, 28, 32-39.
  50. Souiden Y, Mahdouani M, Chaieb K (2010). Polymorphisms of glutathione-S-transferase M1 and T1 and prostate cancer risk in a Tunisian population. Cancer Epidemiol, 34, 598-3.
  51. Steinbrecher A, Rohrmann S, Timofeeva M, et al (2010). Dietary glucosinolate intake, polymorphisms in selected biotransformation enzymes, and risk of prostate cancer. Cancer Epidemiol Biomarkers Prev, 19, 135-43.
  52. Thakur H, Gupta L, Sobti RC, et al (2011). Association of GSTM1T1 genes with COPD and prostate cancer in north Indian population. Mol Biol Rep, 38, 1733-39.
  53. Vijayalakshmi K, Vettriselvi V, Krishnan M, et al (2005). Polymorphisms at GSTM1 and GSTP1 gene loci and risk of prostate cancer in a South Indian population. Asian Pac J Cancer Prev, 6, 309-14.
  54. Wang D, Zhang LM, Zhai JX, et al (2012). GSTM1 and GSTT1 polymorphisms and colorectal cancer risk in Chinese population: a meta-analysis. Int J Colorectal Dis, 27, 901-9.
  55. Ya-lin W, Jun J, Luo-fu W, et al (2005). Polymorphisms of glutathione-S-transferase genes GSTM1 and GSTT1 and prostate cancer risk in Chinese population. Journal of Third Military Medical University, 10.
  56. Yang J, Wu HF, Zhang W, et al (2006). Polymorphisms of metabolic enzyme genes, living habits and prostate cancer susceptibility. Front Biosci, 11, 2052-60.
  57. Yang Q, Du J, Yao X (2013). Significant association of glutathione S-Transferase T1 null genotype with prostate cancer risk: a meta-analysis of 26,393 subjects. PLOS One, 8, 53700.
  58. Zhang J, Grek C, Ye ZW, et al (2014). Pleiotropic functions of glutathione S-transferase P. Adv Cancer Res, 122, 143-75.
  59. Zhang ZJ, Hao K, Shi R, et al (2011). Glutathione S-transferase M1 (GSTM1) and glutathione Stransferase T1 (GSTT1) null polymorphisms, smoking, and their interaction in oral cancer: a huge review and meta-analysis. Am J Epidemiol, 173, 847-57.