Investigation of MDM2 Gene Promoter Polymorphism (SNP309) in Patients with Acute Myeloid Leukemia in Khuzestan Province

Document Type : Original Article

Authors

1 Master of Biology. Department of Biology, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran.

2 Department of Biology,Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz , Iran

3 Assistant Professor of Biology. Department of Pathology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Abstract

Background and Objective: Acute myeloid disease is a genetic disorder resulting from a change in the natural mechanisms of the blood precursor cells such as proliferation and differentiation. Mouse Double Minute 2 (MDM2) is an oncoprotein with E3 ubiquitin ligase activity that acts as a potent negative regulator for P53. The most well-known MDM2 gene polymorphism is SNP309 polymorphism. Substitution of G nucleotide instead of the T at 309 position increases the expression level of the MDM2 gene. Increasing the MDM2 level decrease the activity of p53 which can lead to cancer.
Subjects and Methods: This study was performed on 91 AML blood samples and 115 control blood samples in Khuzestan province. Different genotypes of 309 position of MDM2 genes were determined using PCR-RFLP and Sequeing method.
Results: The results show that there is statistically significant association between MDM2 SNP309 polymorphism and AML.
Conclusion: In this study the frequency of TT, TG, and GG genotypes was 15%, 41% and 43% in AML group and 62%, 22% and 14% in control group respectively. The genotypic distribution of this polymorphism may be strongly associated with AML.

Keywords

References

1-del Pilar Díaz, María, et al. "Cancer incidence pattern in Cordoba, Argentina." European Journal of Cancer Prevention 18.4 (2009): 259-266.
2-Mousavi, Seyed Mohsen, et al. "Cancer incidence and mortality in Iran." Annals of Oncology 20.3 (2009): 556-563.
3-Babaei, Mehdi, et al. "Cancer occurrence in Semnan Province, Iran: results of a population-based cancer registry." Asian Pac J Cancer Prev 6.2 (2005): 159-64.
4-Valbuena JR, Herling M, Admirand JH, Padula A, Jones D, Medeiros LJ. T-cell prolymphocytic leukemia involving extramedullary sites. Am J Clin Pathol 2005; 123:456.
5-Robin O, Mervin C. Hematology and immunology. 1st Ed. Philadelphia: Saunders; 2008
6-Jadidi, R., et al., “Parents a dead end life”: The main experiences of parents of children with leukemia. Iranian journal of nursing and midwifery research, 2014. 19(6): p. 600.
7-Schlenk, R.F., Post-remission therapy for acute myeloid leukemia. haematologica, 2014. 99(11): p. 1663.
8-Lowenberg, B., J.R. Downing, and A. Burnett, Acute myeloid leukemia. New England Journal of
Medicine, 1999. 341(14): p. 1051-1062
9-Estey, E. and H. Döhner, Acute myeloid leukaemia. The Lancet, 2006. 368(9550): p. 1894-1907.
10-K. Ding et al., 2006, Structure-based design of spiro-oxindoles as potent, specific small-molecule inhibitors of the MDM2-p53 interaction, J. Med. Chem. 49, pp. 3432-3435.
11-8.Longo, D. L., et al., Acute myeloid leukaemia. New England Journal of Medicine, 2015. 373(12): p. 1136-1152.
12-Iwakuma, Tomoo, and Guillermina Lozano. "MDM2, an introduction." Molecular Cancer Research 1.14 (2003): 993-1000.
13-Paulin FE, O'Neill M, McGregor G, Cassidy A, Ashfield A, Ali CW, Munro AJ, Baker L, Purdie CA, Lane DP, Thompson AM. MDM2 SNP309 is associated with high grade node positive breast tumours and is in linkage disequilibrium with a novel  MDM2 intron polymorphism. BMC Cancer. 2008 Oct 1;8:281
14-Bond GL, Hirshfield KM, Kirchhoff T, Alexe G, Bond EE, et al. (2006) MDM2 SNP309 accelerates tumor formation in a gender-specific and hormonedependent manner. Cancer Res 66: 5104–5110.
15-Bond GL, Menin C, Bertorelle R, Alhorpuro P, Aaltonen LA, et al. (2006) MDM2 SNP309 Accelerates colorectal tumour formation in women. J Med Genet 43(12): 950–952.
16-Onat OE, Tez M, Ozcelik T, et al. MDM2 T309G polymorphism is associated with bladder cancer. Anticancer Res, 2006, 26: 3473–3475
17-Olivier M, Eeles R, Hollstein M, Khan MA, Harris CC, Hainaut P. (2002). The IARC TP53 database: new online mutation analysis and recommendations to users Hum Mutat 19, 607–614.
18-Phang BH, Linn YC, Li H, Sabapathy K. (2008). MDM2 SNP309 G alleldecreases risk but does not affect onset age or survival of Chinese leukaemia patients. Eur JCancer 44, 760–766.
19-Terry, Kathryn, et al. "MDM2 SNP309 is associated with endometrial cancer risk." Cancer Epidemiology and Prevention Biomarkers 17.4 (2008): 983-986.
20-Knappskog, Stian, et al. "MDM2 Promoter SNP344T> a (rs1196333) status does Not affect cancer risk." PLoS One 7.4 (2012): e36263.
21-Phillips, Christine L., et al. "MDM2 polymorphism increases susceptibility to childhood acute myeloid leukemia: a report from the Children's Oncology Group." Pediatric blood & cancer 55.2 (2010): 248-253
22-Yan, Yu-Lan, et al. "Association between the MDM2 T309G polymorphism and leukemia risk: a metaanalysis." Asian Pac J Cancer Prev 15.16 (2014): 6767-72.
23-Cingeetham, Anuradha, et al. "Role of the MDM2 Promoter Polymorphism (-309T> G) in Acute Myeloid Leukemia Development." Asian Pacific Journal of Cancer Prevention 16.7 (2015): 2707-2712.
24-Ellis, Nathan A., et al. "MDM2 SNP309 and TP53 Arg72Pro interact to alter therapy-related acute myeloid leukemia susceptibility." Blood 112.3 (2008): 741-749.
Jundishapur Scientific Medical Journal
Volume 17, Issue 2 - Serial Number 113
July and August 2018
Pages 187-194

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History

  • Receive Date: 22 January 2018
  • Revise Date: 16 May 2018
  • Accept Date: 20 May 2018

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