Article Data

  • Views 598
  • Dowloads 147

Original Research

Open Access

Polymorphisms of glutathione-s-transferase M1, T1, and P1 genes in endometrial carcinoma

  • K. Ozerkan1
  • M. A. Atalay1,*,
  • T. Yakut2
  • Y. Doster1
  • E. Yilmaz1
  • M. Karkucak2

1Department of Obstetrics and Gynecology, Uludag University, Bursa

2Department of Medical Genetics, Uludag University, Bursa (Turkey).

DOI: 10.12892/ejgo340107 Vol.34,Issue 1,January 2013 pp.42-47

Published: 10 January 2013

*Corresponding Author(s): M. A. Atalay E-mail:


Objective: To investigate the polymorphism rates and possible roles of glutathione-s-transferase M1, T1, and P1 gene polymorphisms in the predisposition to endometrial cancer in Caucasian women. Materials and Methods: Serum samples and medical records were collected from 53 Caucasian women with newly diagnosed endometrial cancer and 67 women of the same race without any known history of cancer. Multiplex polymerase chain reaction (PCR) analysis was used to assess glutathione-s-transferase M1 (GSTM1) and T1 gene polymorphisms. Polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) method was used in salvage of GSTP1 gene polymorphism. Results: Frequencies of GSTM1 and GSTT1 null genotypes were not significantly different between the controls and patients with endometrial cancer (56.7% vs 52.8%, p = 0.671; 32.8% vs 26.4%, p = 0.574, respectively). The authors were not able to demonstrate any association between neither GSTP1 genotypes nor allele frequencies and endometrial carcinoma in the population studied (p = 0.310, p = 0.318, respectively). Moreover, no significant association could be demonstrated with GSTM1 and GSTT1 polymorphisms and clinical stages of endometrial cancer. Nevertheless, there was a significant difference between the frequencies of GSTP1 AA and GG genotypes in relation to Stage I disease when compared with advanced stages of endometrial carcinoma (p = 0.03). In addition, no association was found between polymorphisms of GST suspergene family and non-endometrioid type endometrial carcinomas. Conclusion: These results suggest that GSTT1, GSTM1, and GSTP1 polymorphisms are not associated with endometrial cancer in the Caucasian population.


Polymorphism; Gene; Glutathione-s-transferase; Adenocarcinoma; Carcinoma; Endometrium.

Cite and Share

K. Ozerkan, M. A. Atalay,T. Yakut,Y. Doster,E. Yilmaz,M. Karkucak. Polymorphisms of glutathione-s-transferase M1, T1, and P1 genes in endometrial carcinoma. European Journal of Gynaecological Oncology. 2013. 34(1);42-47.


[1] Coleman M.P., Esteve J., Damiecki P., Arslan A., Renard H.: “Trends in cancer incidence and mortality”. 1st ed., Lyon, International Agency for Research an Cancer 1993, IARC, Scientific Publication 121.

[2] United States Cancer Statistics Working Group. United States Cancer Statistics: 1999 incidence. Atlanta: Department of Health and Human Services, Centers for Disease Control and Prevention and National Cancer Institute; 2002.

[3] Barakat R.R.: “Contemporary issues in the management of endometrial cancer”. CA Cancer J. Clin., 1998, 48, 299.

[4] Carbone M., Pass H.I.: “Multistep and multifactorial carcinogenesis: When does a contributing factor become a carcinogen?”. Semin. Cancer Biol., 2004, 14, 399.

[5] Strange R.C., Spiteri M.A., Ramachandran S., Fryer A.A.: “Glutathione-S-transferase family of enzymes”. Mutat. Res., 2001, 482, 21.

[6] Rebbeck T.R.: “Molecular epidemiology of the human glutathione S-transferase genotypes GSTM1, and GSTT1 in cancer susceptibility”. Cancer Epidemiol. Biomarkers Prev., 1997, 6, 733.

[7] Hayes J.D., Pulford D.J.: “The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance”. Crit. Rev. Biochem. Mol. Biol., 1995, 30, 445.

[8] Beckett G.J., Hayes J.D.: “Glutathione S-transferases: biomedical applications”. Adv. Clin. Chem., 1993, 30, 281.

[9] Seidegård J., Ekström G.: “The role of human glutathione transferases and epoxide hydrolases in the metabolism of xenobiotics”. Environ Health Perspect., 1997, 105, 791.

[10] Spencer S.R., Xue L.A., Klenz E.M., Talalay P.: “The potency of inducers of NAD(P)H: (quinone-acceptor) oxidoreductase parallels their efficiency as substrates for glutathione transferases. Structural and electronic correlations”. Biochem J., 1991, 273, 711.

[11] Mandel H.G., Manson M.M., Judah D.J., Simpson J.L., Green J.A., Forrester L.M. et al.: “Metabolic basis for the protective effect of the antioxidant ethoxyquin on aflatoxin B1 hepatocarcinogenesis in the rat”. Cancer Res., 1987, 47, 5218.

[12] Homma H., Maruyama H., Niitsu Y., Listowsky I.: “A subclass of glutathione S-transferases as intracellular high-capacity and highaffinity steroid-binding proteins”. Biochem. J., 1986, 235, 763.

[13] Danger D.P., Baldwin W.S., LeBlanc G.A.: “Photoaffinity labelling of steroid-hormone-binding glutathione S-transferases with [3H]methyltrienolone. Inhibition of steroid-binding activity by the anticarcinogen indole-3-carbinol”. Biochem. J., 1992, 288, 361.

[14] Frova C.: “Glutathione transferases in the genomics era: New insights and perspectives”. Biomol. Eng., 2006, 23, 149.

[15] Hayes J.D., Strange R.C.: “Glutathione S-transferase polymorphisms and their biological consequences”. Pharmacology, 2000, 61, 154.

[16] Zhong S.L., Zhou S.F., Chen X., Chan S.Y., Chan E., Ng K.Y. et al.: “Relationship between genotype and enzyme activity of glutathione S-transferases M1 and P1 in Chinese”. Eur. J. Pharm. Sci., 2006, 28, 77.

[17] Millikan R., Pittman G., Tse C.K., Savitz D.A., Newman B., Bell D.: “Glutathione S-transferases M1, T1, and P1 and breast cancer”. Cancer Epidemiol. Biomarkers Prev., 2000, 9, 567.

[18] Rossini A., Rapozo D.C., Amorim L.M., Macedo J.M., Medina R., Neto J.F. et al.: “Frequencies of GSTM1, GSTT1, and GSTP1 polymorphisms in a Brazilian population”. Genet. Mol. Res., 2002, 1, 233.

[19] Ada A.O., Süzen S.H., Iscan M.: “Polymorphisms of cytochrome P450 1A1, glutathione S-transferases M1 and T1 in a Turkish population”. Toxicol. Lett., 2004, 151, 311.

[20] Shi X., Zhou S., Wang Z., Zhou Z., Wang Z.: “CYP1A1 and GSTM1 polymorphisms and lung cancer risk in Chinese populations: a meta-analysis”. Lung Cancer, 2008, 59, 155.

[21] Srivastava D.S., Mishra D.K., Mandhani A., Mittal B., Kumar A., Mittal R.D.: “Association of genetic polymorphism of glutathione S-transferase M1, T1, P1 and susceptibility to bladder cancer”. Eur. Urol., 2005, 48, 339.

[22] Ramalhinho A.C., Fonseca-Moutinho J.A., Breitenfeld Granadeiro L.A.: “Positive association of polymorphisms in estrogen biosynthesis gene, CYP19A1, and metabolism, GST, in breast cancer susceptibility”. DNA Cell. Biol., 2012, 31, 1100. Epub 2012 Feb. 2.

[23] Ate N.A., Tamer L., Ate C., Ercan B., Elipek T., Ocal K., Camdeviren H.: “Glutathione S-transferase M1, T1, P1 genotypes and risk for development of colorectal cancer”. Biochem. Genet., 2005, 43, 149.

[24] Schneider J., Efferth T., Rodriguez-Escudero F.J., Volm M.: “Intrinsic overexpression of two different mechanisms of resistance to chemotherapy (P-glycoprotein and GST-pi) in human endometrial carcinoma”. Chemotherapy, 1994, 40, 265.

[25] Yokoyama Y., Maruyama H., Sato S., Saito Y.: “Risk factors predictive of para-aortic lymph node metastasis in endometrial carcinomas”. J. Obstet. Gynaecol. Res., 1997, 23, 179.

[26] Yokoyama Y., Sagara M., Sato S., Saito Y.: “Value of glutathione S-transferase pi and the oncogene products c-Jun, c-Fos, c-H-Ras, and c-Myc as a prognostic indicator in endometrial carcinomas”. Gynecol. Oncol., 1998, 68, 280.

[27] Ueda M., Hung Y.C., 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, 16, 241.

[28] Karageorgi S., Prescott J., Wong J.Y., Lee I.M., Buring J.E., De Vivo I.: “GSTM1 and GSTT1 copy number variation in population-based studies of endometrial cancer risk”. Cancer Epidemiol. Biomarkers Prev., 2011, 20, 1447.

[29] FIGO. Annual report on the results of treatment in gynecologic cancer. Int. J. Gynecol. Obstet., 1989, 28, 189.

[30] Lin D.X., Tang Y.M., Peng Q., Lu S.X., Ambrosone C.B., Kadlubar F.F.: “Susceptibility to esophageal cancer and genetic polymorphisms in glutathione S-transferases T1, P1, and M1 and cytochrome P450 2E1”. Cancer Epidemiol. Biomarkers Prev., 1998, 7, 1013.

[31] Harries L.W., Stubbins M.J., Forman D., Howard G.C., Wolf C.R.: “Identification of genetic polymorphisms at the glutathione Stransferase Pi locus and association with susceptibility to bladder, testicular and prostate cancer”. Carcinogenesis, 1997, 18, 641.

[32] Mannervik B., Danielson U.H.: “Glutathione transferases: structure and catalytic activity”. Crit. Rev. Biochem. Mol. Biol., 1988, 23, 281.

[33] Satoh T., Nishida M., Oki A., Nishide K., Tsunoda H., Kubo T.: “An immunohistological study on expression of glutathione Stransferase pi (form) in human endometrial carcinoma”. Nippon Sanka Fujinka Gakkai Zasshi, 1996, 48, 133.

[34] Nakachi K., Imai K., Hayashi S., Kawajiri K.: “Polymorphisms of the CYP1A1 and glutathione S-transferase genes associated with susceptibility to lung cancer in relation to cigarette dose in a Japanese population”. Cancer Res., 1993, 53, 2994.

[35] Zhong S., Howie A.F., Ketterer B., Taylor J.B., Hayes J.D., Beckett G.J. et al.: “Glutathione S transferase mu locus: use of genotyping and phenotyping assays to assess association with lung cancer susceptibility”. Carcinogenesis, 1991, 12, 1533.

[36] Brockmoller J., Kerb R., Drakoulis N., Staffeldt B., Roots I.: “Glutathione S-transferase M1 and its variants A and B as host factors of bladder cancer susceptibility: a case control study”. Cancer Res., 1994, 54, 4103.

[37] Hosgood H.D. 3rd, Berndt S.I., Lan Q.: “GST genotypes and lung cancer susceptibility in Asian populations with indoor air pollution exposures: a meta-analysis”. Mutat. Res., 2007, 636, 134.

[38] Vlaykova T., Miteva L., Gulubova M., Stanilova S.: “Ile105Val GSTP1 polymorphism and susceptibility to colorectal carcinoma in Bulgarian population”. Int. J. Colorectal. Dis., 2007, 22, 1209.

[39] Kim S.U., Lee K.M., Park S.K., Yoo K.Y., Noh D.Y., Choe K.J. et al.: “Genetic polymorphism of glutathione S-transferase P1 and breast cancer risk”. J. Biochem. Mol. Biol., 2004, 37, 582.

[40] Chan Q.K.Y., Khoo U.S., Ngan H.Y.S., Yang C.Q., Xue W.C., Chan K.Y.K. et al.: “Single nucleotide polymorphism of pi-class glutathione s-transferase and susceptibility to endometrial carcinoma”. Clin. Cancer Res., 2005, 11, 2981.

[41] Chan Q.K.Y., Khoo U.S., Chan K.Y.K., Ngan H.Y.S., Li S.S., Chiu P.M. et al.: “Promoter methylation and differential expression of pi class gluthathione s-transferase in endometrial carcinoma”. J. Mol. Diagn., 2005, 7, 8.

Abstracted / indexed in

Science Citation Index Expanded (SciSearch) Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,500 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.

Biological Abstracts Easily discover critical journal coverage of the life sciences with Biological Abstracts, produced by the Web of Science Group, with topics ranging from botany to microbiology to pharmacology. Including BIOSIS indexing and MeSH terms, specialized indexing in Biological Abstracts helps you to discover more accurate, context-sensitive results.

Google Scholar Google Scholar is a freely accessible web search engine that indexes the full text or metadata of scholarly literature across an array of publishing formats and disciplines.

JournalSeek Genamics JournalSeek is the largest completely categorized database of freely available journal information available on the internet. The database presently contains 39226 titles. Journal information includes the description (aims and scope), journal abbreviation, journal homepage link, subject category and ISSN.

Current Contents - Clinical Medicine Current Contents - Clinical Medicine provides easy access to complete tables of contents, abstracts, bibliographic information and all other significant items in recently published issues from over 1,000 leading journals in clinical medicine.

BIOSIS Previews BIOSIS Previews is an English-language, bibliographic database service, with abstracts and citation indexing. It is part of Clarivate Analytics Web of Science suite. BIOSIS Previews indexes data from 1926 to the present.

Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.

Submission Turnaround Time