Genetic polymorphisms of glutathione S transferase and cervical intraepithelial neoplasia

Open access


Aim: The present study aim to analyze the relationship between GST M/T genotypes of glutathione S-transferases and cervical intraepithelial neoplasia.

Materials and Methods: A prospective case-control study has been designed including 69 cases with different degrees of cervical dysplasia and 107 controls. All patients had been examined colposcopically. For every patient both cervical and blood specimen have been obtained. The peripheral blood was used for GST M/T genotyping. The statistical analysis was performed using OR and chi-square at a level of significance inferior to 0.05.

Results: No statistically significant differences had been found between cases and controls for GST T-/M- geno-type (T-/M-, χ2=0.03, p= 0.8610) and T+/M+ χ2=0.65, p = 0.4197. Patients with in situ carcinoma had significant GST genotype association for T-/M+ genotype (OR=4.66, CI 95% [0.6528,24.9725], χ2=4.6, p=0.0314) and for T+/M- genotype (OR=0.12, CI 95% [0.0027,0.9465], χ2=0.05, p=0.0219).

Conclusion: The combination of GST genotypes can be included in a predictive score for patients with cervical carcinoma.

1. Faridi R, Zahra A, Khan K, Idrees M. Oncogenic potential of Human Papillomavirus (HPV) and its relation with cervical cancer. Virol J. 2011 Jun;8:269. DOI: 10.1186/1743-422X-8-269.

2. Stanley MA. Pathology and epidemiology of HPV infection in females. Gynecol Oncol. 2010 May;117(2 Suppl):S5-10. DOI: 10.1016/j.ygyno.2010.01.024

3. Parkin D. The global health burden of infection associated cancers in the year 2002. Int J Cancer. 2006 Jun;118(12):3030-44. DOI: 10.1002/ijc.21731.

4. Ibeanu OA. Molecular pathogenesis of cervical cancer. Cancer Biology & Therapy Cancer Biol Ther. 2011 Feb;11(3):295-306. DOI: 10.4161/cbt.11.3.14686.

5. Fernandes JV, Araújo JMG, Fernandes TAAM. Biology and natural history of human papillomavirus infection. Open Access Journal of Clinical Trials.2013;5:1–12. DOI: 10.2147/OAJCT.S37741.

6. Yugawa T, Kiyono T. Molecular mechanisms of cervical carcinogenesis by high-risk human papillomaviruses: novel functions of E6 and E7 oncoproteins. Rev Med Virol. 2009 Mar;19(2):97-113. DOI: 10.1002/rmv.605.

7. Habbous S, Pang V, Eng L, Xu W, Kurtz G, Liu FF, et al. p53 Arg72Pro polymorphism, HPV status and initiation, progression, and development of cervical cancer: a systematic review and meta-analysis. Clin Cancer Res. 2012 Dec;18(23):6407-15. DOI: 10.1158/1078-0432.CCR-12-1983.

8. Nunobiki O, Ueda M, Toji E, Yamamoto M, Akashi K, Sato N, et al. Genetic Polymorphism of Cancer Susceptibility Genes and HPV Infection in Cervical Carcinogenesis. Patholog Res Int. 2011;2011:364069. DOI: 10.4061/2011/364069.

9. Tsigris C, Chatzitheofylaktou A, Xiromeritis C, Nikiteas N, Yannopoulos A. Genetic association studies in digestive system malignancies. Anticancer Res. 2007 Sep-Oct;27(5B):3577-87.

10. Moore EE, Wark JD, Hopper JL, Erbas B, Garland SM. The roles of genetic and environmental factors on risk of cervical cancer: a review of classical twin studies. Twin Res Hum Genet. 2012 Feb;15(1):79-86. DOI: 10.1375/twin.15.1.79.

11. Ueda M, Hung YC, Terai Y, Kanda K, Takehara M, Yamashita H, et al. Glutathione S-transferase GSTM1, GSTT1 and p53 codon 72 polymorphisms in human tumor cells. Hum Cell. 2003 Dec;16(4):241-51. DOI: 10.1111/j.1749-0774.2003.tb00158.x.

12. Wang D, Wang B, Zhai JX, Liu DW, Sun GG. Glutathione S-transferase M1 and T1 polymorphisms and cervical cancer risk: a meta-analysis. Neoplasma. 2011;58(4):352-9. DOI: 10.4149/neo_2011_04_352.

13. Zhen S, Hu C-M, Bian L-H. Glutathione S-Transferase Polymorphism Interactions with Smoking Status and HPV Infection in Cervical Cancer Risk: An Evidence-Based Meta-Analysis. PLoS One. 2013 Dec 31;8(12):e83497. DOI: 10.1371/journal.pone.0083497.

14. de Carvalho CR, Silva ID, Pereira JS, de Souza CN, Focchi GR, Ribalta JC. Polymorphisms of p53, GSTM1 and GSTT1, and HPV in uterine cervix adenocarcinoma. Eur J Gynaecol Oncol. 2008;29(6):590-3.

15. Ueda M, Hung YC, Terai Y, Kanda K, Takehara M, Yamashita H et al. Glutathione S-transferase GSTM1, GSTT1 and p53 codon 72 polymorphisms in human tumor cells. Hum Cell. 2003 Dec;16(4):241-51. DOI: 10.1111/j.1749-0774.2003.tb00158.x.

16. Economopoulos KP, Choussein S, Vlahos NF, Sergentanis TN. GSTM1 polymorphism, GSTT1 polymorphism, and cervical cancer risk: a meta-analysis. Int J Gynecol Cancer. 2010 Dec;20(9):1576-80.

17. Solomon D, Davey D, Kurman R, Moriarty A, O’Connor D, Prey M, et al. The 2001 Bethesda System: terminology for reporting results of cervical cytology. JAMA. 2002 Apr 24;287(16):2114-9. DOI: 10.1001/jama.287.16.2114.

18. Bornstein J, Bentley J, Bösze P, Girardi F, Haefner H, Menton M, et al. 2011 colposcopic terminology of the International Federation for Cervical Pathology and Colposcopy. Obstet Gynecol. 2012 Jul;120(1):166-72. DOI: 10.1097/AOG.0b013e318254f90c.

19. Darragh TM, Colgan TJ, Cox JT, Heller DS, Henry MR, Luff RD, et al; Members of LAST Project Work Groups. The Lower Anogenital Squamous Terminology Standardization Project for HPV-Associated Lesions: background and consensus recommendations from the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology. J Low Genit Tract Dis. 2012 Jul;16(3):205-42. DOI: 10.1097/LGT.0b013e31825c31dd.

20. Bid HK, Konwar R, Saxena M, Chaudhari P, Agrawal CG, Banerjee M. Association of glutathione S-transferase (GSTM1, T1 and P1) gene polymorphisms with type 2 diabetes mellitus in north Indian population. J Postgrad Med. 2010 Jul-Sep;56(3):176-81. DOI: 10.4103/0022-3859.68633.

21. Peralta-Zaragoza O, Bermúdez-Morales VH, Pérez-Plasencia C, Salazar-León J, Gómez-Cerón C, Madrid-Marina V. Targeted treatments for cervical cancer: a review. Onco Targets Ther. 2012;5:315-28. DOI: 10.2147/OTT.S25123.

22. Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, et al. Human papilloma-virus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999 Sep;189(1):12-9. DOI: 10.1002/(SICI)1096-9896(199909)189:1<12::AID-PATH431>3.0.CO;2-F.

23. Woodman CB, Collins SI, Young LS. The natural history of cervical HPV infection: unresolved issues. Nat Rev Cancer. 2007 Jan;7(1):11-22. DOI: 10.1038/nrc2050.

24. de Sanjose S, Quint WG, Alemany L, Geraets DT, Klaustermeier JE, Tous S, et al: Retrospective International Survey and HPV Time Trends Study Group: Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study. Lancet Oncol. 2010 Nov;11(11):1048-56. DOI: 10.1016/S1470-2045(10)70230-8.

25. Chattopadhyay K. A comprehensive review on host genetic susceptibility to human papillomavirus infection and progression to cervical cancer. Indian J Hum Genet. 2011 Sep;17(3):132-44. DOI: 10.4103/0971-6866.92087.

26. Zoodsma M, Sijmons RH, de Vries EG, Zee AG. Familial cervical cancer: case reports, review and clinical implications. Hered Cancer Clin Pract. 2004 May 15;2(2):99-105. DOI: 10.1186/1897-4287-2-2-99.

27. Liu Y, Xu LZ. Meta-analysis of association between GSTM1 gene polymorphism and cervical cancer. Asian Pac J Trop Med. 2012 Jun;5(6):480-4. DOI: 10.1016/S1995-7645(12)60083-2.

28. 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. 2010 Sep;21(3):169-73. DOI: 10.3802/jgo.2010.21.3.169.

29. Ster AM, Petrisor FM, Stan C, Pop VI. Gluthathion S-transferase M1 and T1 polymorpisms in a group of Romanian glaucoma patients. Rev Romana Med Lab. 2015;23(4):506-10. DOI: 10.1515/rrlm-2015-0048.

30. Catana A, Popp R, Pop M, Porojan M, Pop V, Trifa A, Petrisor F, Farcas M. Genetic polymorphism of alpha 1 antytrypsin and glutathione S transferase and lung cancer risk. European Respiratory Journal 2011 38: p1966.

31. Cseh J, Pazsit E, Orsos Z, Marek E, Huszar A, Balogh S, et al. Effect of Glutathione-S-Transferase M1 and T1 Allelic Polymorphisms on HPV-induced Cervical Precancer Formation. Anticancer Res. 2011 Sep;31(9):3051-5.

32. Goodman MT, McDuffie K, Hernandez B, Bertram CC, Wilkens LR, Guo C, et al. CYP1A1, GSTM1, and GSTT1 polymorphisms and the risk of cervical squamous intraepithelial lesions in a multiethnic population. Gynecol Oncol. 2001 May;81(2):263-9. DOI: 10.1006/gyno.2001.6154.

33. Gao LB, Pan XM, Li LJ, Liang WB, Bai P, Rao L, et al. Null genotypes of GSTM1 and GSTT1 contribute to risk of cervical neoplasia: an evidence-based meta-analysis. PLoS One. 2011;6(5):e20157. DOI: 10.1371/journal.pone.0020157.

34. McIntyre-Seltman K, Castle PE, Guido R, Schiffman M, Wheeler CM. Smoking is a risk factor for cervical intraepithelial neoplasia grade 3 among oncogenic human papillomavirus DNA-positive women with equivocal or mildly abnormal cytology. Cancer Epidemiol Biomarkers Prev. 2005 May;14(5):1165-70. DOI: 10.1158/1055-9965.EPI-04-0918.

35. Sheehan D, Meade G, Foley VM, Dowd CA. Structure, function and evolution of glutathione transferases: implications for classification of non-mammalian members of an ancient enzyme superfamily. Biochem J. 2001 Nov;360(Pt 1):1-16. DOI: 10.1042/bj3600001.

36. Fonseca-Moutinho JA. Smoking and Cervical Cancer. ISRN Obstet Gynecol. 2011;2011:847684. DOI: 10.5402/2011/847684.

37. Collins S, Rollason TP, Young LS, Woodman CBJ. Cigarette smoking is an independent risk factor for cervical intraepithelial neoplasia in young women: a longitudinal study. Eur J Cancer. 2010 Jan;46(2):405-11. DOI: 10.1016/j.ejca.2009.09.015.

38. Byrne MM, Davila EP, Zhao W, Parker D, Hooper MW, Caban-Martinez A, et al. Cancer screening behaviors among smokers and non-smokers. Cancer Epidemiol. 2010 Oct;34(5):611-7. DOI: 10.1016/j.canep.2010.06.017.

39. Louie KS, Castellsague X, de Sanjose S, Herrero R, Meijer CJ, Shah K, et al. Smoking and passive smoking in cervical cancer risk: pooled analysis of couples from the IARC multicentric case-control studies. Cancer Epidemiol Biomarkers Prev. 2011 Jul;20(7):1379-90. DOI: 10.1158/1055-9965.EPI-11-0284.

40. Abbas M, Srivastava K, Imran M, Banerjee M. Association of Glutathione S-transferase (GSTM1, GSTT1 and GSTP1) polymorphisms and passive smoking in cervical cancer cases from North India. Int J Biomed Res. 2013;4:655-62. DOI: 10.7439/ijbr.v4i12.396.

41. Sui Y, Han W, Yang Z, Jiang M. Association of glutathione S-transferase M1 and T1 null polymorphisms with the development of cervical lesions: a meta-analysis. Eur J Obstet Gynecol Reprod Biol. 2011 Dec;159(2):443-8. DOI: 10.1016/j.ejogrb.2011.09.012.

42. Rodríguez M, Mejia F, Lecourtois M, Domínguez V, Castillo J. Influence of GSTT1, GSTM1 and GSTP1 Polymorphisms on the Development of Breast Cancer. J Cancer Ther. 2014;5:552-9. DOI: 10.4236/jct.2014.56063.

43. Oliveira AL, Rodrigues FF, Santos RE, Aoki T, Rocha MN, Longui CA, et al. GSTT1, GSTM1, and GSTP1 polymorphisms and chemotherapy response in locally advanced breast cancer. Genet Mol Res. 2010 Jun 11;9(2):1045-53. DOI: 10.4238/vol9-2gmr726.

Revista Romana de Medicina de Laborator

Romanian Journal of Laboratory Medicine

Journal Information

IMPACT FACTOR 2017: 0.400
5-year IMPACT FACTOR: 0.320

CiteScore 2017: 0.31

SCImago Journal Rank (SJR) 2017: 0.144
Source Normalized Impact per Paper (SNIP) 2017: 0.195


All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 187 186 14
PDF Downloads 67 67 7