Glutathione-S-Transferase T1 Polymorphism is Associated with Esophageal Cancer Risk in Chinese Han Population

  • Weng, Yuan (Department of Thoracic and Cardiovascular Surgery, No.4 people's hospital of Wuxi City) ;
  • Fei, Bojian (Department of Surgical Oncology, No.4 people's hospital of Wuxi City) ;
  • He, Ping (Department of Surgical Oncology, No.4 people's hospital of Wuxi City) ;
  • Cai, Ming (Department of Thoracic and Cardiovascular Surgery, No.4 people's hospital of Wuxi City)
  • Published : 2012.09.30


Background: Glutathione-S-Transferase T1 (GSTT1) gene has been shown to be involved in the development of esophageal cancer. However, the results have been inconsistent. In this study, the authors performed a meta-analysis to clarify the association between GSTT1 polymorphism and esophageal cancer risk among Chinese Han population. Methods: Published literature from PubMed, the China National Knowledge Infrastructure and Wanfang Data were searched. Pooled odds ratio (OR) and 95% confidence interval (95%CI) was calculated using a fixed- or random-effects model. Results: Eleven studies with a total of 2779 individuals were included in the meta-analysis. The results showed that GSTT1 null genotype was significantly associated with esophageal cancer risk in Chinese (OR = 1.31, 95%CI 1.12 to 1.53, p = 0.001). Further sensitivity analyses confirmed the significant association. The cumulative meta-analysis showed a trend of an obvious association between GSTT1 null genotype and esophageal cancer risk as information accumulated by year. Conclusions: This meta-analysis suggests a significant association of GSTT1 null genotype with esophageal cancer risk in the Chinese Han population.


  1. Cochran WG (1954). The combination of estimates from different experiments. Biometrics, 10, 101-29.
  2. Deng J, Guo R, Yue H, et al (2008). A case-control study of the polymorphism of Phase I and Phase II metabolic genes and esophageal carcinoma susceptibility. Shiyong Xin Nao Xue Guan Bing Za Zhi, 16, 16-7.
  3. DerSimonian R, Laird N (1986). Meta-analysis in clinical trials. Control Clin Trials, 7, 177-88.
  4. Dong LM, Potter JD, White E, et al (2008). Genetic susceptibility to cancer: the role of polymorphisms in candidate genes. JAMA, 299, 2423-36.
  5. Egger M, Davey Smith G, Schneider M, et al (1997). Bias in meta-analysis detected by a simple, graphical test. BMJ, 315, 629-34.
  6. Fang Y, Xiao F, An Z, et al (2011). Systematic review on the relationship between genetic polymorphisms of methylenetetrahydrofolate reductase and esophageal squamous cell carcinoma. Asian Pac J Cancer Prev, 12, 1861-6.
  7. Gao CM, Takezaki T, Wu JZ, et al (2002). Glutathione-Stransferases M1 (GSTM1) and GSTT1 genotype, smoking, consumption of alcohol and tea and risk of esophageal and stomach cancers: a case-control study of a high-incidence area in Jiangsu Province, China. Cancer Lett, 188, 95-102.
  8. Gao P, Qian Y, Ye X, et al (2012). Study of CYP1A1, GSTM1, GSTT1 polymorphisms and susceptibility on esophageal carcinoma in Ninxia Hui nationality. Ningxia Medical Journal, 34, 196-9.
  9. Hayes JD, Strange RC (2000). Glutathione S-transferase polymorphisms and their biological consequences. Pharmacology, 61, 154-66.
  10. Hayes JD, Flanagan JU, Jowsey IR (2005). Glutathione transferases. Annu Rev Pharmacol Toxicol, 45, 51-88.
  11. Hiyama T, Yoshihara M, Tanaka S, et al (2007). Genetic polymorphisms and esophageal cancer risk. Int J Cancer, 121, 1643-58.
  12. Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90.
  13. Ji R, Wu J, Zhou Y, et al (2010). Relationship between CYP1A1, GSTM1 and GSTT1 genetic polymorphisms and susceptibility of esophageal cancer in Wuwei, Gansu province. J Lanzhou Univ (Medical Sciences), 36, 29-34.
  14. Kumar V, Murthy AK, Suresh KP (2011). Glutathione S-transferase M1 and T1 status and the risk of laryngeal cancer: a meta-analysis. Asian Pac J Cancer Prev, 12, 2221-6.
  15. Lao-Sirieix P, Caldas C, Fitzgerald RC (2010). Genetic predisposition to gastro-oesophageal cancer. Curr Opin Genet Dev, 20, 210-7.
  16. Lau J, Antman EM, Jimenez-Silva J, et al (1992). Cumulative meta-analysis of therapeutic trials for myocardial infarction. N Engl J Med, 327, 248-54.
  17. Lin DX, Tang YM, Peng Q, et al (1998). Susceptibility to esophageal cancer and genetic polymorphisms in glutathione S-transferases T1, P1, and M1 and cytochrome P450 2E1. Cancer Epidemiol Biomarkers Prev, 7, 1013-8.
  18. Liu R, Yin L, Pu Y, et al (2010). Functional alterations in the glutathione S-transferase family associated with enhanced occurrence of esophageal carcinoma in China. J Toxicol Environ Health A, 73, 471-82.
  19. Mantel N, Haenszel W (1959). Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst, 22, 719-48.
  20. Mao WM, Zheng WH, Ling ZQ (2011). Epidemiologic risk factors for esophageal cancer development. Asian Pac J Cancer Prev, 12, 2461-6.
  21. Oakley A (2011). Glutathione transferases: a structural perspective. Drug Metab Rev, 43, 138-51.
  22. Pearson WR, Vorachek WR, Xu SJ, et al (1993). Identification of class-mu glutathione transferase genes GSTM1-GSTM5 on human chromosome 1p13. Am J Hum Genet, 53, 220-33.
  23. Pera M, Manterola C, Vidal O, et al (2005). Epidemiology of esophageal adenocarcinoma. J Surg Oncol, 92, 151-9.
  24. Qiu LX, Yuan H, Yu KD, et al (2010). Glutathione S-transferase M1 polymorphism and breast cancer susceptibility: a metaanalysis involving 46,281 subjects. Breast Cancer Res Treat, 121, 703-8.
  25. Qiu LX, Wang K, Lv FF, et al (2011). GSTM1 null allele is a risk factor for gastric cancer development in Asians. Cytokine, 55, 122-5.
  26. Raza H (2011). Dual localization of glutathione S-transferase in the cytosol and mitochondria: implications in oxidative stress, toxicity and disease. FEBS J, 278, 4243-51.
  27. Roth MJ, Abnet CC, Johnson LL, et al (2004). Polymorphic variation of Cyp1A1 is associated with the risk of gastric cardia cancer: a prospective case-cohort study of cytochrome P-450 1A1 and GST enzymes. Cancer Causes Control, 15, 1077-83.
  28. Strange RC, Spiteri MA, Ramachandran S, et al (2001). Glutathione-S-transferase family of enzymes. Mutat Res, 482, 21-6.
  29. Tan W, Song N, Wang GQ, et al (2000). Impact of genetic polymorphisms in cytochrome P450 2E1 and glutathione S-transferases M1, T1, and P1 on susceptibility to esophageal cancer among high-risk individuals in China. Cancer Epidemiol Biomarkers Prev, 9, 551-6.
  30. Thallinger CM, Raderer M, Hejna M (2011). Esophageal cancer: a critical evaluation of systemic second-line therapy. J Clin Oncol, 29, 4709-14.
  31. Wang B, Huang G, Wang D, et al (2010). Null genotypes of GSTM1 and GSTT1 contribute to hepatocellular carcinoma risk: evidence from an updated meta-analysis. J Hepatol, 53, 508-18.
  32. Wang LD, Zheng S, Liu B, et al (2003). CYP1A1, GSTs and mEH polymorphisms and susceptibility to esophageal carcinoma: study of population from a high- incidence area in north China. World J Gastroenterol, 9, 1394-7.
  33. Yang L, Parkin DM, Li L, et al (2003). Time trends in cancer mortality in China: 1987-1999. Int J Cancer, 106, 771-83.
  34. Yi LH, Pu YP, Song YH, et al (2005). Polymorphisms of susceptible genes for esophageal cancer risk in Huaian population in Jiangsu province. Zhong Liu, 25, 357-61.
  35. Zhang LW, Yi L, Wu M, et al (2009). Study on relations between genetic polymorphisms in CYP2C19, GSTT1 and risk of Kazakh's esophageal cancer in Xinjiang. J Pract Oncol, 24, 232-6.
  36. Zhang ZJ, Hao K, Shi R, et al (2011). Glutathione S-transferase M1 (GSTM1) and glutathione S-transferase T1 (GSTT1) null polymorphisms, smoking, and their interaction in oral cancer: a HuGE review and meta-analysis. Am J Epidemiol, 173, 847-57.
  37. Zhang ZY, Jin XY, Wu R, et al (2012). Meta-analysis of the association between GSTM1 and GSTT1 gene polymorphisms and cervical cancer. Asian Pac J Cancer Prev, 13, 815-9.
  38. Zhuo WL, Zhang YS, Wang Y, et al (2009). Association studies of CYP1A1 and GSTM1 polymorphisms with esophageal cancer risk: evidence-based meta-analyses. Arch Med Res, 40, 169-79.

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