Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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MDM2 T309G has a Synergistic Effect with P21 ser31arg Single Nucleotide Polymorphisms on the Risk of Acute Myeloid Leukemia

  • Ebid, Gamal T. (Clinical Pathology Department, National Cancer Institute, Cairo University) ;
  • Sedhom, Iman A. (Pediatric Oncology Department, National Cancer Institute, Cairo University) ;
  • El-Gammal, Mosaad M. (Medical Oncolog Departement, National Cancer Institute, Cairo University) ;
  • Moneer, Manar M. (Medical Biostatistic Departement, National Cancer Institute, Cairo University)
  • Published : 2012.09.30
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Abstract

Background: The P53 tumor suppressor gene plays a pivotal role in maintaining cellular homeostasis by preventing the propagation of genome mutations. P53 in its transcriptionally active form is capable of activating distinct target genes that contribute to either apoptosis or growth arrest, like P21. However, the MDM2 gene is a major negative regulator of P53. Single nucleotide polymorphisms (SNP) in codon Arg72Pro of P53 results in impairment of the tumor suppressor activity of the gene. A similar effect is caused by a SNP in codon 31 of P21. In contrast, a SNP in position 309 of MDM2 results in increased expression due to substitution of thymine by guanine. All three polymorphisms have been associated with increased risk of tumorigenesis. Aim of the study: We aimed to study the prevalence of SNPs in the P53 pathway involving the three genes, P53, P21 and MDM2, among acute myeloid leukemia (AML) patients and to compare it to apparently normal healthy controls for assessment of impact on risk. Results: We found that the P21 ser31arg heterozygous polymorphism increases the risk of AML (P value=0.017, OR=2.946, 95% CI=1.216-7.134). Although the MDM2 309G allele was itself without affect, it showed a synergistic effect with P21 ser/arg polymorphism (P value=0.003, OR=6.807, 95% CI=1.909-24.629). However, the MDM2 309T allele abolish risk effect of the P21 polymorphic allele (P value=0.71). There is no significant association of P53 arg72pro polymorphism on the risk of AML. Conclusion: We suggest that SNPs in the P53 pathway, especially the P21 ser31arg polymorphism and combined polymorphisms especially the P21/MDM2 might be genetic susceptibility factors in the pathogenesis of AML.

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References

  1. Ara S, Lee PS, Hansen MF, Saya H (1990). Codon 72 polymorphism of the TP53 gene. Nucleic Acids Res, 18, 496.
  2. Bond GL, Hirshfield KM, Kirchhoff T, et al (2006). MDM2 SNP 309 accelerates tumor formation in a gender-specific and hormone dependent manner. Cancer Res, 66, 5104-10. https://doi.org/10.1158/0008-5472.CAN-06-0180
  3. Bond GL, Hu W, Levine A (2005). A single nucleotide polymorphism in the MDM2 gene from a molecular and cellular explanation to clinical effect. Cancer Res, 65, 5481-4. https://doi.org/10.1158/0008-5472.CAN-05-0825
  4. Bozzone DM (2009). The biology of cancer: Leukemia. Chelsea house, an imprint of InfoBase Publishing, New York.
  5. Chen WC, Wu HC, Hsu CD, Chen HY, Tsai FJ (2002). P21 gene codon 31 polymorphism is associated with bladder cancer. Urol Oncol, 7, 63-6. https://doi.org/10.1016/S1078-1439(01)00152-1
  6. Ellis NA, Huo D, Yildiz O, et al (2008). MDM2 SNP309 and TP53 Arg72Pro interact to alter therapy-related acute myeloid leukemia susceptibility. Blood, 112, 458-9. https://doi.org/10.1182/blood-2008-05-156703
  7. Gupta RC, Earley K, Sharma S (1988). Use of human peripheral blood lymphocytes to measure DNA binding capacity of chemical carsinogens. Proc Natl Acad Sci USA, 85, 3513-7. https://doi.org/10.1073/pnas.85.10.3513
  8. Haupt Y, Maya R, Kazaz A, Oren M (1997). Mdm2 promotes the rapid degradation of p53. Nature, 387, 296-9. https://doi.org/10.1038/387296a0
  9. Hirata H, Hinoda Y, Kikuno N, et al (2007). MDM2 SNP 309 polymorphism as risk factor for susceptibility and poor prognosis in renal cell carcinoma. Clin Cancer Res, 13, 4123-29. https://doi.org/10.1158/1078-0432.CCR-07-0609
  10. Ishibe N, Wiencke JK, Zuo ZF, et al (1997). Susceptibility to lung cancer in light smokers associated with CYP1A1 polymorphisms in Mexican- and African-Americans. Cancer Epidemiol Biomarkers Prev, 6, 1075-80.
  11. Jiang P, Liu J, Li w, et al (2010). Role of p53 and p21 polymorphisms in the risk of cervical cancer among Chinese women. Acta Biochim Biophys Sin, 42, 671-6. https://doi.org/10.1093/abbs/gmq069
  12. Levine AJ (1997). P53, the cellular gatekeeper for growth and division. Cell, 88, 323-31. https://doi.org/10.1016/S0092-8674(00)81871-1
  13. Matakidou A, Eisen T, Houlston RS (2003). TP53 polymorphisms and lung cancer risk: a systematic review and meta-analysis. Mutagenesis, 18, 377-85. https://doi.org/10.1093/mutage/geg008
  14. Miliani de Marval PL, Zhang Y (2011). The RP-MDM2-P53 pathway and tumorigenesis. Mar, 2, 234-8
  15. Nakano Y, T Naoe, H Kiyoi, et al (2000). Poor clinical significance of p53 gene polymorphism in acute myeloid leukemia. Leuk Res, 24, 349-52. https://doi.org/10.1016/S0145-2126(99)00187-3
  16. Onel K, Cordon-Cardo C (2004). MDM2 and prognosis. Mol Cancer Res, 2, 1-8.
  17. Phang B, Linn Y, Li H, Sabapathy K (2008). MDM2 SNP309 G allele decreases risk but does not affect onset age or survival of Chinese leukaemia patients. Eur J Cancer, 449, 760-6.
  18. Read AP, Strachan T (1999). Cancer genetics. Chapter 18, human molecular genetics. New York: Wiley-Liss. Publishers Taylor and Francis Group.
  19. Sotamaa K, Liyanarachchi S, Mecklin JP, et al (2005). P53 codon 72 and MDM2 SNP309 polymorphisms and age of colorectal cancer onset in Lynch syndrome. Clin Cancer Res, 11, 6840-4. https://doi.org/10.1158/1078-0432.CCR-05-1139
  20. Taghavi N, Biramijamal F, Abbaszadegan MR, et al (2010). P21 (Waf1/Cip1) gene polymorphisms and possible interaction with cigarette smoking in esophageal squamous cell carcinoma in Northeastern Iran: a preliminary study. National institute of genetic engineering and biotechnology (NIGEB), Tehran. Arch Iran Med, 13, 235-42.
  21. Weston A, Godbold JH (1997). Polymorphisms of H-ras-1 and p53 in breast cancer and lung cancer: a meta-analysis. Environ Health Perspect, 105, 919-26. https://doi.org/10.1289/ehp.97105s4919
  22. Wojcik I, Szybka M, Golanska E, et al (2005). Abnormalities of the P53, MDM2, BCL2 and BAX genes in acute leukemias. Neoplasma, 52, 318-24.
  23. WrenschKelsey KT, Liu M, McMillan A, et al (2005). CYP1A1 variants and smoking-related lung cancer in San Francisco Bay area Latinos and African Americans. Int J Cancer, 113, 141-7. https://doi.org/10.1002/ijc.20537
  24. Xiong X, Wang M, Wang L, et al (2009). Risk of MDM2 SNP309 alone or in combination with the p53 codon 72 polymorphism in acute myeloid leukemia. Leuk Res, 33, 1454-8. https://doi.org/10.1016/j.leukres.2009.04.007

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