GSTP1 (Ile105Val) Gene Polymorphism: Risk and Treatment Response in Chronic Myeloid Leukemia

Shereen Elhoseiny, Mohamed El-Wakil, Mohamed Fawzy, Aya Abdel Rahman

Department of Clinical and Chemical Pathology, Beni Suef Teaching Hospital, Beni Suef University, Beni Suef, Egypt.
Department of Clinical Oncology, Beni Suef Teaching Hospital, Beni Suef University, Beni Suef, Egypt.
Department of Pediatric Oncology, National Cancer Institute, Cairo University, Egypt.

DOI: 10.4236/jct.2014.51001                

Abstract

Background: Genetic variation influencing individual susceptibility to chemical carcinogens is one of the main factors leading to cancer development. The glutathione S-transferases (GSTs) are a family of enzymes belonging to phase II enzymes involved in detoxification of xenobiotics. A significant relationship is observed between the risk of developing cancer and genetic polymorphisms within GSTs. Methods: In this study, we investigated the influence of inherited GSTP1 (Ile105Val) gene polymorphism on the susceptibility to CML in Egypt in 40 CML patients (20 children and 20 adults), together with 40 healthy controls using a [PCR-RFLP] assay. Results: We found that the mutant type (IIe/Val, Val/Val) was significantly higher in CML patients (67.5%) compared to controls (35%) (p = 0.004); [odds ratio 3.9; 95% CI: 1.5 - 9.7]. The mutant type was associated with more advanced phases in disease and with both worse hematological and cytogenetic responses when compared to the wild type (p = 0.03, p = 0.05, and p < 0.001, respectively). Conclusion: GSTP1 (Ile105Val) gene polymorphism conferred a significant association with increased risk of CML and is associated with worse prognosis. Further studies on the functional consequences of this genetic polymorphism would pave the way to declare its role in the pathogenesis of CML or as a possible predictor for response to therapy.

Keywords

CML; GSTs; GSTP1 (Ile105Val)

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	M. E. O’Dwyer, M. J. Mauro and B. J. Druker, “Recent Advancements in the Treatment of Chronic Myelogenous Leukemia,” Annual Review of Medicine, Vol. 53, 2002, pp. 369-381. http://dx.doi.org/10.1146/annurev.med.53.082901.103853
[2]	G. S. Lordelo, A. L. Miranda-Vilela, A. K. Akimoto, et al., “Association between Methylene Tetrahydrofolate Reductase and Glutathione S-Transferase M1 Gene Polymorphisms and Chronic Myeloid Leukemia in a Brazilian Population,” Genetics and Molecular Research, Vol. 11, No. 2, 2012, pp. 1013-1026. http://dx.doi.org/10.4238/2012.April.19.6
[3]	A. Hishida, S. Terakura, N. Emi, et al., “GSTT1 and GSTM1 Deletions, NQO1 C609T Polymorphism and Risk of Chronic Myelogenous Leukemia in Japanese,” Asian Pacific Journal of Cancer Prevention, Vol. 6, No. 3, 2005, pp. 251-255.
[4]	M. Taspinar, S. E. Aydos, O. Comez, et al., “CYP1A1, GST Gene Polymorphisms and Risk of Chronic Myeloid Leukemia,” Swiss Medical Weekly, Vol. 138, No. 1-2, 2008, pp. 12-17.
[5]	C. J. Omiecinski, J. P. Vanden Heuvel, G. H. Perdew, et al., “Xenobiotic Metabolism, Disposition, and Regulation by Receptors: From Biochemical Phenomenon to Predictors of Major Toxicities,” Toxicological Sciences, Vol. 120, No. S1, 2011, pp. S49-S75. http://dx.doi.org/10.1093/toxsci/kfq338
[6]	G. Bhat, A. Bhat, A. Wani, et al., “Polymorphic Variation in Glutathione-S-Transferase Genes and Risk of Chronic Myeloid Leukaemia in the Kashmiri Population,” Asian Pacific Journal of Cancer Prevention, Vol. 13, No. 1, 2012, pp. 69-73. http://dx.doi.org/10.7314/APJCP.2012.13.1.069
[7]	B. Mannervik, “The Isozymes of Glutathione S-Transferase,” Advances in Enzymology, Vol. 57, 1985, pp. 357-417.
[8]	R. C. Strange, M. A. Spiteri, S. Ramachandran, et al., “Glutathione-S-Transferase Family of Enzymes,” Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 482, No. 1-2, 2001, pp. 21-26. http://dx.doi.org/10.1016/S0027-5107(01)00206-8
[9]	H. Autrup, “Genetic Polymorphisms in Human Xenobiotica Metabolizimg Enzymes as Susceptibility Factors in Toxic Response,” Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 464, No. 1, 2000, pp. 65-76. http://dx.doi.org/10.1016/S1383-5718(99)00167-9
[10]	S. Landi, “Mammalian Class Theta GST and Differential Susceptibility to Carcinogens: A Review,” Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 463, No. 3, 2000, pp. 247-283. http://dx.doi.org/10.1016/S1383-5742(00)00050-8
[11]	S. Tsuchida and K. Sato, “Glutathione Transferases and Cancer,” Critical Reviews in Biochemistry and Molecular Biology, Vol. 27, No. 4-5, 1992, pp. 337-384. http://dx.doi.org/10.3109/10409239209 082566
[12]	N. R. Dunna, S. Vuree, S. Kagita, et al., “Association of GSTP1 Gene (I105V) Polymorphism with Acute Leukaemia,” Journal of Genetics, Vol. 91, 2012, pp. e60-e63.
[13]	World Medical Association, “Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects,” The 59th WMA General Assembly, Seoul, 2008.
[14]	F. Millot, A. Baruchel, J. Guilhot, et al., “Imatinib Is Effective in Children with Previously Untreated Chronic Myelogenous Leukemia in Early Chronic Phase: Results of the French National Phase IV Trial,” Journal of Clinical Oncology, Vol. 29, No. 20, 2011, pp. 2827-2832. http://dx.doi.org/10. 1200/JCO.2010.32.7114
[15]	S. Saussele, M. Lauseker, A. Gratwohl, et al., “Allogeneic Hematopoietic Stem Cell Transplantation (Allo SCT) for Chronic Myeloid Leukemia in the Imatinib Era: Evaluation of Its Impact within a Subgroup of the Randomized German CML Study IV,” Blood, Vol. 115, No. 10, 2010, pp. 1880-1885. http://dx.doi.org/10.1182/blood-2009-08-237115
[16]	J. R. Andolina, S. M. Neudorf and S. J. Corey, “How I Treat Childhood CML,” Blood, Vol. 119, No. 8, 2012, pp. 1821-1830. http://dx.doi.org/10.1182/blood-2011-10-380774
[17]	K. Sailaja, D. Surekha, D. N. Rao, et al., “Association of the GSTP1 Gene (Ile105Val) Polymorphism with Chronic Myeloid Leukemia,” Asian Pacific Journal of Cancer Prevention, Vol. 11, No. 2, 2010, pp. 461-464.
[18]	T. Ishii, T. Matsuse, S. Teramoto, et al., “Glutathione S-Transferase P1 (GSTP1) Polymorphism in Patients with Chronic Obstructive Pulmonary Disease,” Thorax, Vol. 54, No. 8, 1999, pp. 693-696. http://dx.doi.org/10.1136/thx.54.8.693
[19]	B. Dawson and R. G. Trapp, “Basic and Clinical Biostatistics,” 3rd Edition, McGraw-Hill Inc., 2001.
[20]	B. Kiran, M. Karkucak, H. Ozan, et al., “GST (GSTM1, GSTT1 and GSTP1) Polymorphisms in the Genetic Susceptibility of Turkish Patients to Cervical Cancer,” Journal of Gynecologic Oncology, Vol. 21, No. 3, 2010, pp. 169-173. http://dx.doi.org/10.3802/jgo.2010.21.3.169
[21]	Z. Ye and H. Song, “Glutathione s-Transferase Polymorphisms (GSTM1, GSTP1 and GSTT1) and the Risk of Acute Leukaemia: A Systematic Review and Meta-Analysis,” European Journal of Cancer, Vol. 41, No. 7, 2005, pp. 980-989. http://dx.doi.org/10.1016/j.ejca.2005.01.014
[22]	M. Karkucak, T. Yakut, T. Gulten, et al., “Investigation of GSTP1 (Ile105Val) Gene Polymorphism in Chronic Myeloid Leukaemia Patients,” International Journal of Human Genetics, Vol. 12, No. 3, 2012, pp. 145-149.
[23]	L. W. Harries, M. J. Stubbins, D. Forman, et al., “Identification of Gentic Polymorphisms at the Glutathione S-Tranferase Pilocus and Association with Susceptibility to Bladder, Testicular and Prostate Cancer,” Carcinogenesis, Vol. 18, No. 4, 1997, pp. 641-644. http://dx.doi.org/10.1093/ carcin/18.4.641
[24]	D. Ryberg, V. Skaug, A. Hewer, et al., “Genotypes of Glutathione Transferase M1 and P1 and Their Significance for Lung DNA Adduct Levels and Cancer Risk,” Carcinogenesis, Vol. 18, No. 7, 1997, pp. 1285-1289. http://dx.doi.org/10.1093/carcin/18.7.1285
[25]	K. J. Helzlsouer, O. Selmin, H. Y. Huang, et al., “Association between Glutathione S-Transferase M1, P1, and T1 Genetic Polymorphisms and Development of Breast Cancer,” Journal of the National Cancer Institute (Bethesda), Vol. 90, No. 7, 1998, pp. 512-518. http://dx.doi.org/10.1093/jnci/ 90.7.512
[26]	V. Maggini, G. Buda, S. Galimberti, et al., “Lack of Association of NQO1 and GSTP1 Polymorphisms with Multiple Myeloma Risk,” Leukemia Research, Vol. 32, No. 6, 2008, pp. 988-990. http://dx.doi.org/10.1016/j.leukres.2007.10.008
[27]	J. D. Hayes and D. J. Pulford, “The Glutathione S-Transferase Supergene Family: Regulation of GST and the Contributions of the Isoenzymes to Cancer Chemoprotection and Drug Resistance,” Critical Reviews in Biochemistry and Molecular Biology, Vol. 30, No. 6, 1995, pp. 445-600. http://dx.doi.org/ 10.3109/10409239509083491