Author(s): Chunmei Liu, Yan Zeng, Xizhen Ma, Yuewen Qi, Shuai Zhang, Rui Lv, Hong Yu
Objective: To study the influence of GSTM1 and GSTT1 gene polymorphisms on cervical cancer (CC) risk, and explore genetic-environmental interactions. Methods: After a systematic literature search, all relevant studies entailing the association between GST polymorphisms and CC were included. The pooled odds ratio (OR) was used for analysis of the results and corresponding 95% confidence intervals (CI) were estimated. Results: A total of 23 case-control studies were included in the meta-analysis of GSTM1 (2,250 CC cases and 3,025 controls) and GSTT1 (1,704 CC cases and 2,460 controls) genotypes. For the GSTM1 polymorphisms, the null genotype of GSTM1 was associated with an increased CC risk for the total population (OR=1.57, 95% CI=1.25-1.98). A similar association was found in China (OR=2.34, 95% CI=1.56-3.52), India (OR=2.02, 95% CI=1.43-2.83), Pakistan (OR=5.52, 95% CI=2.34-13.07), Serbia (OR=1.73, 95% CI=0.68-4.39) and Kazakhstan (OR=6.5, 95% CI=2.25-18.81), but was not noted for others countries. Regarding human papilloma virus (HPV) infection, moderately but significantly increased risk of the null GSTM1 genotype was found in HPV-positive patients (OR=2.59, 95% CI=1.57-4.27). For the GSTT1 polymorphisms, the null GSTT1 genotype was associated with increased CC risk in the total population (OR=1.44, 95% CI=1.07-1.93). Regarding ethnic stratification, a significantly increased risk of the null GSTT1 genotype was found in Kazakhstan (OR=3.99, 95% CI=2.56-6.21) and Brazil (OR=4.58, 95% CI=2.04-10.28). With respect to smoking, the two aspects of the analysis above were not significantly associated with CC risk in smokers or non-smokers, respectively. For the GSTM1/GSTT1 interaction analysis, the dual null genotypes of GSTM1/GSTT1 were significantly associated with increased CC risk for the total population (OR=1.62, 95% CI=1.14-2.29). Conclusion: This meta-analysis provided sufficient evidence that the null genotype of GSTM1, or GSTT1 and the dual-null genotypes of GSTM1/GSTT1 are associated with CC.
Cervical cancer, genetic polymorphism, glutathione S-transferase M1, glutathione S-transferase T1, meta-analysis
- Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics. CA Cancer J Clin 65: 87-108, 2015.
- Cancer IAfRo. Cervical Cancer incidence and mortality worldwide in 2008[J]. Extraído de, acesso em [11 de abril de 2013]. 2012.
- Schiffman M, Castle PE, Jeronimo J, Rodriguez AC and Wacholder S: Human papillomavirus and cervical cancer. Lancet. 370: 890-907, 2007.
- Wang SS, Bratti MC, Rodriguez AC, Herrero R, Burk RD, Porras C, et al: Common variants in immune and DNA repair genes and risk for human papillomavirus persistence and progression to cervical cancer. J Infect Dis 199: 20-30, 2009.
- Miller III MC, Mohrenweiser HW and Bell DA: Genetic variability in susceptibility and response to toxicants. Toxicol Lett 120: 259-268, 2001.
- Singh H, Sachan R, Devi S, Pandey SN and Mittal B: Association of GSTM1, GSTT1, and GSTM3 gene polymorphisms and susceptibility to cervical cancer in a North Indian population. Am J Obstet Gynecol 198: 303 e1-6, 2008.
- Agodi A, Barchitta M, Cipresso R, Marzagalli R, La Rosa N, Caruso M, et al: Distribution of p53, GST, and MTHFR polymorphisms and risk of cervical intraepithelial lesions in sicily. Int J Gynecol Cancer 20: 141-146, 2010.
- Song G, Song Z, Xu J and Shao S: Association of single nucleotide polymorphism in glutathione S-transferase-M1 with susceptibility to cervical cancer in Shanxi Province. Chin J Cancer Prev Treat 15: 1054-1056, 2008,.
- Higgins J and Thompson SG: Quantifying heterogeneity in a meta‐analysis. Stat Me 21: 1539-1558, 2002.
- Warwick A, Redman C, Jones P, Fryer A, Gilford J, Alldersea J, et al: Progression of cervical intraepithelial neoplasia to cervical cancer: interactions of cytochrome P450 CYP2D6 EM and glutathione s-transferase GSTM1 null genotypes and cigarette smoking. Brit J Cancer 70: 704, 1994.
- Sharma A, Gupta S, Sodhani P, Singh V, Sehgal A, Sardana S, et al: Glutathione S-transferase M1 and T1 Polymorphisms, Cigarette Smoking and HPV Infection in Precancerous and Cancerous Lesions of the Uterine Cervix. Asian Pac Cancer Prev 16:6429, 2015.
- Sharma A, Sharma J, Murthy N, and Mitra A: Polymorphisms at GSTM1 and GSTT1 gene loci and susceptibility to cervical cancer in Indian population. Neoplasma 51: 12-16, 2003.
- Kiran B, Karkucak M, Ozan H, Yakut T, Ozerkan K, Sag S, et al: GST (GSTM1, GSTT1, and GSTP1) polymorphisms in the genetic susceptibility of Turkish patients to cervical cancer. J Gynecol Oncol 21: 169-173, 2001.
- Chen C, Madeleine MM, Weiss NS and Daling JR: Glutathione S-transferase M1 genotypes and the risk of squamous carcinoma of the cervix: a population-based case-control study. Am J Epidemiol 150: 568-572, 1999.
- Stosic I, Grujicic D, Arsenijevic S, Brkic M and Milosevic-Djordjevic O. Glutathione S-transferase T1 and M1 polymorphisms and risk of uterine cervical lesions in women from central Serbia. Asian Pac J Cancer Prev 15: 3201-3205, 2013.
- Kim JW, Lee CG, Park YG, Kim KS, Kim IK, Sohn YW, et al: Combined analysis of germline polymorphisms of p53, GSTM1, GSTT1, CYP1A1, and CYP2E1. Cancer 88: 2082-2091, 2000.
- Djansugurova LB, Perfilyeva AV, Zhunusova GS, Djantaeva KB, Iksan OA and Khussainova EM: The determination of genetic markers of age-related cancer pathologies in populations from Kazakhstan. Frontiers in Genetics 4: 70 , 2013.
- Yao L, Wenjing M and Qing L: Association between genetic polymorphism of GSTM1, CYP2E1 and susceptibility to cervical cancer and its precancerous lesions in Uighur women in Xinjiang. Prog Obstet Gynecol 11: 012, 2009.
- Ma C, Liu Y, Lu X and Ma H: The relationship between GSTM1 and incidence of cervical cancer in Uighur women in xinjiang. Chin J Obstet Gynecol 44: 629-631, 2009.
- Ueda M, Toji E, Nunobiki O, Sato N, Izuma S, Torii K, et al: Germline polymorphisms of glutathione-S-transferase GSTM1, GSTT1 and p53 codon 72 in cervical carcinogenesis. Human cell. 23: 119-125, 2010.
- Palma S, Novelli F, Padua L, Venuti A, Prignano G, Mariani L, et al: Interaction between glutathione-S-transferase polymorphisms, smoking habit, and HPV infection in cervical cancer risk. J Cancer Res Clin Oncol 136: 1101-1109, 2010.
- Sobti R, Kaur S, Kaur P, Singh J, Gupta I, Jain V, et al: Interaction of passive smoking with GST (GSTM1, GSTT1, and GSTP1) genotypes in the risk of cervical cancer in India. Cancer Genet Cytogen 166: 117-123, 2006.
- Lee S-A, Kim JW, Roh JW, Choi JY, Lee K-M, Yoo K-Y, et al: Genetic polymorphisms of GSTM1, p21, p53 and HPV infection with cervical cancer in Korean women. Gynecol Oncol 93: 14-18, 2004.
- Hasan S, Hameed A, Saleem S, Shahid S, Haider G and Azhar A: The association of GSTM1 and GSTT1 polymorphisms with squamous cell carcinoma of cervix in Pakistan. Tumor Biol 36: 5195-5199, 2015.
- Natphopsuk S, Settheetham-Ishida W, Settheetham D and Ishida T: Lack of Participation of the GSTM1 Polymorphism in Cervical Cancer Development in Northeast Thailand. Asian Pac J Cancer Prev 16: 1935-1937, 2014.
- Settheetham-Ishida W, Yuenyao P, Kularbkaew C, Settheetham D and Ishida T: Glutathione S-transferase (GSTM1 and GSTT1) polymorphisms in cervical cancer in Northeastern Thailand. Asian Pac J Cancer Prev 10: 365-368, 2009.
- Niwa Y, Hirose K, Nakanishi T, Nawa A, Kuzuya K, Tajima K, et al: Association of the NAD(P)H: quinone oxidoreductase C609T polymorphism and the risk of cervical cancer in Japanese subjects. Gynecol Oncol 96: 423-429, 2005.
- Zhou Q, Wang J, Shao S, Ma XC Ding L: The study of the relationship between glutathione S-transferase M1, T1 genotypes and the risk of cervical cancer. Modern Prev Med 33: 269-271, 2006.
- Warwick A, Sarhanis P, Redman C, Pemble S, Taylor JB, Ketterer B, et al: Theta class glutathione S-transferase GSTT1 genotypes and susceptibility to cervical neoplasia: interactions with GSTM1, CYP2D6 and smoking. Carcinogenesis 15: 2841-2845, 1994.
- De Carvalho C, da Silva I, Pereira J, de Souza N, Focchi G and Ribalta J: Polymorphisms of p53, GSTM1 and GSTT1, and HPV in uterine cervix adenocarcinoma. Eur J Gynaecol Oncol 29: 590-593, 2007.
- Prokopczyk B, Cox JE and Hoffmann D: Identification of tobacco-specific carcinogen in the cervical mucus of smokers and nonsmokers. J Natl Cancer Inst 89: 868-873, 1997.
- Wang D, Wang B, Zhai J, Liu D and Sun G: Glutathione S-transferase Ml and T1 polymorphisms and cervical cancer risk: A meta-analysis. Neoplasma 58: 352, 2011.
- Zeller JL, Lynm C and Glass RM: Carcinoma of the Cervix. J Am Med Assoc 298: 2336-2336, 2007.
- Wacholder S, Silverman DT, McLaughlin JK and Mandel JS: Selection of controls in case-control studies: II. Types of controls. Am J Pidemiol 135(9):1029-41, 1992.
International Journal of Sciences is Open Access Journal.
This article is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) License.
Author(s) retain the copyrights of this article, though, publication rights are with Alkhaer Publications.