The Study of TAAAA Repeat Polymorphism in p53 Gene and Its Association with Prostate Cancer

Document Type : Original Article (s)

Authors

1 MSc Student, Department of Biology, School of Science, University of Isfahan, Isfahan, Iran

2 Associate Professor, Department of Biology, School of Science, University of Isfahan, Isfahan, Iran

3 Assistant Professor, Department of Radiotherapy, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

4 Department of Biology, School of Science, University of Isfahan, Isfahan, Iran

Abstract

Background: Prostate cancer has a high degree of heterogeneity in pathology and clinical appearance. In response to stress, P53 plays an important role in preventing cancer development. To our knowledge, this is the first report about polymorphic TAAAA repeat of the P53 gene and its relation to prostate cancer risk. The purpose of this study was to investigate polymorphism of TAAAA in the first intron of p53 gene among prostate cancer patients and healthy individuals and its relation to risk of prostate cancer.Methods: A total of 306 peripheral blood samples consisting of 156 from patients with prostate cancer and 150 from healthy control individuals were included in the study. DNA was extracted from blood using salting-out method. TAAAA repeat sequences were amplified by PCR technique and the length of products was determined by polyacrylamide gel and direct sequencing.Findings: Based on our results, 5 alleles and 12 different genotypes for P53 TAAAA repeat polymorphism were observed. The most common allele in both patients and controls was the allele 8/8. Men who carry 9/9 or 10/10 genotypes of p53 gene are at significantly higher risk of prostate cancer. The allelic length of p53 polymorphisms had no significant effect on age of onset, inheritance as well as metastasis.Conclusion: Our study showed a strong association between the TAAAA repeat polymorphism in P53 gene and risk of prostate cancer.

Keywords


  1. Caini S, Gandini S, Dudas M, Bremer V, Severi E, Gherasim A. Sexually transmitted infections and prostate cancer risk: a systematic review and meta-analysis. Cancer Epidemiol 2014; 38(4): 329-38.
  2. Djulbegovic M, Beyth RJ, Neuberger MM, Stoffs TL, Vieweg J, Djulbegovic B, et al. Screening for prostate cancer: systematic review and meta-analysis of randomised controlled trials. BMJ 2010; 341: c4543.
  3. Yaghi MD, Kehinde EO. Oral antibiotics in trans-rectal prostate biopsy and its efficacy to reduce infectious complications: Systematic review. Urol Ann 2015; 7(4): 417-27.
  4. Beuzeboc P, Soulie M, Richaud P, Salomon L, Staerman F, Peyromaure M, et al. Fusion genes and prostate cancer. From discovery to prognosis and therapeutic perspectives. Prog Urol 2009; 19(11): 819-24. [In French].
  5. Eliyahu D, Raz A, Gruss P, Givol D, Oren M. Participation of p53 cellular tumour antigen in transformation of normal embryonic cells. Nature 1984; 312(5995): 646-9.
  6. Lane DP, Benchimol S. p53: oncogene or anti-oncogene? Genes Dev 1990; 4(1): 1-8.
  7. Oliner JD, Kinzler KW, Meltzer PS, George DL, Vogelstein B. Amplification of a gene encoding a p53-associated protein in human sarcomas. Nature 1992; 358(6381): 80-3.
  8. Wu M, Wang X, McGregor N, Pienta KJ, Zhang J. Dynamic regulation of Rad51 by E2F1 and p53 in prostate cancer cells upon drug-induced DNA damage under hypoxia. Mol Pharmacol 2014; 85(6): 866-76.
  9. Baumann K. Cell death: multitasking p53 promotes necrosis. Nat Rev Mol Cell Biol 2012; 13(8): 480-1.
  10. Ringer L, Sirajuddin P, Tricoli L, Waye S, Choudhry MU, Parasido E, et al. The induction of the p53 tumor suppressor protein bridges the apoptotic and autophagic signaling pathways to regulate cell death in prostate cancer cells. Oncotarget 2014; 5(21): 10678-91.
  11. Soussi T, Caron de FC, May P. Structural aspects of the p53 protein in relation to gene evolution. Oncogene 1990; 5(7): 945-52.
  12. Hainaut P, Hollstein M. p53 and human cancer: the first ten thousand mutations. Adv Cancer Res 2000; 77: 81-137.
  13. Cho Y, Gorina S, Jeffrey PD, Pavletich NP. Crystal structure of a p53 tumor suppressor-DNA complex: understanding tumorigenic mutations. Science 1994; 265(5170): 346-55.
  14. Petitjean A, Mathe E, Kato S, Ishioka C, Tavtigian SV, Hainaut P, et al. Impact of mutant p53 functional properties on TP53 mutation patterns and tumor phenotype: lessons from recent developments in the IARC TP53 database. Hum Mutat 2007; 28(6): 622-9.
  15. Uemura H, Kura Y, Ando N, Fukushima E, Hatanaka Y, Yamamoto Y, et al. Functional evaluation of synchronous inactivation of PTEN and P53 in a murine model of prostate cancer. Cancer Res 2014; 74(19 Supplement): 84.
  16. Dean JL, Jones JK, Goodwin JF, Knudsen KE. Determining the impact of CRPC-specific p53 mutation on therapeutic response and prostate tumor progression. Cancer Res 2015; 75(15 Supplement): 1217.
  17. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988; 16(3): 1215.
  18. Najafi-Dorche S, Tavassoli M, Hemati S, Safari F. The study of TAAAA polymorphism in p53 gene and its association with breast cancer. J Isfahan Med Sch 2015; 33(323): 134-43. [In Persian].
  19. Oren M, Rotter V. Mutant p53 gain-of-function in cancer. Cold Spring Harb Perspect Biol 2010; 2(2): a001107.
  20. Vinall RL, Chen JQ, Hubbard NE, Sulaimon SS, Shen MM, Devere White RW, et al. Initiation of prostate cancer in mice by Tp53R270H: evidence for an alternative molecular progression. Dis Model Mech 2012; 5(6): 914-20.
  21. Ecke TH, Schlechte HH, Schiemenz K, Sachs MD, Lenk SV, Rudolph BD, et al. TP53 gene mutations in prostate cancer progression. Anticancer Res 2010; 30(5): 1579-86.
  22. Goldstein AS, Huang J, Guo C, Garraway IP, Witte ON. Identification of a cell of origin for human prostate cancer. Science 2010; 329(5991): 568-71.
  23. Gemayel R, Cho J, Boeynaems S, Verstrepen KJ. Beyond junk-variable tandem repeats as facilitators of rapid evolution of regulatory and coding sequences. Genes (Basel) 2012; 3(3): 461-80.
  24. Hui J, Reither G, Bindereif A. Novel functional role of CA repeats and hnRNP L in RNA stability. RNA 2003; 9(8): 931-6.
  25. Hui J, Stangl K, Lane WS, Bindereif A. HnRNP L stimulates splicing of the eNOS gene by binding to variable-length CA repeats. Nat Struct Biol 2003; 10(1): 33-7.