DOI QR코드

DOI QR Code

The TP53 intron 6 G13964C Polymorphism and Risk of Thyroid and Breast Cancer Development in the Iranian Azeri Population

  • Dehghan, Roghayeh (Department of Biology, Tabriz University) ;
  • Feizi, Mohammad Ali Hosseinpour (Department of Biology, Tabriz University) ;
  • Pouladi, Nasser (Department of Biology, Tabriz University) ;
  • Adampourezare, Mina (Department of Biology, Tabriz University) ;
  • Farajzadeh, Davoud (Department of Cellular and Molecular Biology, Azarbaijan Shahid Madani University)
  • Published : 2015.04.14

Abstract

Background: TP53 mutations are the most common genetic alterations in human cancers. There are also several polymorphisms in both exons and introns of TP53 that may influence its anti-tumor functions and increase the risk of cancer development. Associations of the TP53 intron 6 G13964C polymorphism with increased risk of development of several cancers have been investigated in numerous studies, but the results were controversial and conflicting. In this study, we aimed to investigate the probable association of this polymorphism with risk of both thyroid and breast cancers among the Iranian-Azeri population. Materials and Methods: We performed two separate case control studies on associations of the intron 6 polymorphism with two different kinds of cancer. In one case-control study, a total of 75 patients with thyroid carcinoma and 180 controls were analyzed and the other study included 170 patients with breast cancer and 135 healthy women. The intron 6 genotype was determined by RFLP-PCR and the SPSS 16 program was applied for data analysis. Results: For thyroid cancer, the frequencies of GG genotype were 96.0% in patients and 93.3% in controls. The GC genotype had a frequency of 4.0 % in patients and 6.7% in controls. In the study on breast cancer, the frequency of GG and GC genotypes in patients were 95.3% and 4.7%, respectively. In breast related control group, the frequency of GG genotype was 93.3 % and the frequency of GC genotype was 6.7%. None of the cases and controls had the CC genotype. Conclusions: There was no significant association between the TP53 intron 6 G13964C polymorphism and risk of development of both thyroid and breast cancer in Iranian-Azeri patients.

Keywords

Thyroid;breast;cancer;P53 tumor suppressor protein;polymorphism;molecular marker

Acknowledgement

Supported by : Azarbaijan Shahid Madani University

References

  1. Akbari M, Abachizadeh K, Khayamzadeh M, et al (2008). Iran cancer report. Cancer Research Center. Shahid Beheshti University of Medical Sciences. Tehran, Qom: Darolfekr. 101-6.
  2. Akbari ME, Rafiee M, Khoei MA, et al (2011). Incidence and survival of cancers in the elderly population in Iran: 2001- 2005. Asian Pac J Cancer Prev, 12, 3035-9.
  3. Alawadi S, Ghabreau L, Alsaleh M, et al (2011). 53 gene polymorphisms and breast cancer risk in Arab women. Med Oncol, 28, 709-715. https://doi.org/10.1007/s12032-010-9505-4
  4. Buller RE, Skilling JS, Kaliszewski S, et al (1995). Absence of significant germline p53 mutations in ovarian cancer patients. Gynecologic Oncology, 58, 368-74. https://doi.org/10.1006/gyno.1995.1244
  5. Buyru N, Tezol A, Dalay N (2005). p53 intronic G13964C variant in colon cancer and its association with HPV. Anticancer Res, 25, 2767-9.
  6. Dehghan R, Hosseinpour Feizi MA, Pouladi N, et al (2014). Association of TP53 (-16ins-Pro) haplotype with the decreased risk of differentiated thyroid carcinoma in Iranian-Azeri Patients. Pathol Oncol Res, 20.
  7. Duntas L, Grab-Duntas BM (2006). Risk and prognostic factors for differentiated thyroid cancer. Hell J Nucl Med, 9, 156-62.
  8. Khayamzadeh M, Khayamzadeh M, Tadayon M, et al (2011). Survival of thyroid cancer and social determinants in Iran, 2001-2005. Asian Pac J Cancer Prev, 12, 95-98.
  9. Langerod A, Zhao H, Borgan O, et al (2007). TP53 mutation status and gene expression profiles are powerful prognostic markers of breast cancer. Breast Cancer Res, 9, 30. https://doi.org/10.1186/bcr1675
  10. Legakis I, Syrigos K (2011). Recent advances in molecular diagnosis of thyroid cancer. J Thyroid res, 384213.
  11. Lehman TA, Haffty BG, Carbone CJ, et al (2000). Elevated frequency and functional activity of a specific germ-line P53 intron mutation in familial breast cancer. Cancer Research, 60, 1062-9.
  12. Liu X, Sinn HP, Ulmer HU, et al (2004). Intronic TP53 germline sequence variants modify the risk in german breast/ovarian cancer families. Hered Cancer Clin Pract, 2, 139-45. https://doi.org/10.1186/1897-4287-2-3-139
  13. Lowenstein D, Kasper D, Braunwald E, et al (2008). Harrison's principles of internal medicine. McGraw-hill Medical Publishing Division, New Delhi.
  14. Machado-Silva A, Perrier S, Bourdon JC (2010). P53 family members in cancer diagnosis and treatment. Semin Cancer Biol, 20, 57-62. https://doi.org/10.1016/j.semcancer.2010.02.005
  15. Malkinson AM, You M (1994). The intronic structure of cancer-related genes regulates susceptibility to cancer. Mol Carcinog, 10, 61-5. https://doi.org/10.1002/mc.2940100202
  16. Marsh A, Spurdle AB, Turner BC, et al (2001). The intronic G13964C variant in p53 is not a high-risk mutation in familial breast cancer in Australia. Breast Cancer Research, 3, 346-9. https://doi.org/10.1186/bcr319
  17. Montagna C, Di Cristofano A (2011). Thyrocyte-specific inactivation of P53 and Pten results in anaplastic thyroid carcinomas faithfully recapitulating human tumors. Oncotarget, 2, 1109-26. https://doi.org/10.18632/oncotarget.380
  18. Nikiforov YE, Biddinger PW, Thompson LDR (2009). Diagnostic pathology and molecular genetics of the thyroid. Baltimore, MD: Lippincott Williams and Wilkins, 94-102.
  19. Olivier M, Goldgar DE, Sodha N, et al (2003). Li-Fraumeni and related syndromes: correlation between tumor type, family structure, and TP53 genotype. Cancer Res, 63, 6643-50.
  20. Olivier M, Hainaut P (2001). TP53 mutation patterns in breast cancers: searching for clues of environmental carcinogenesis. Semin Cancer Biol, 11, 353-60. https://doi.org/10.1006/scbi.2001.0390
  21. Olivier M, Langerod A, Carrieri P, et al (2006). The clinical value of somatic TP53 gene mutations in 1,794 patients with breast cancer. Clin Cancer Res, 12, 1157-67. https://doi.org/10.1158/1078-0432.CCR-05-1029
  22. Parameswaran R, Brooks S, Sadler GP (2010). Molecular pathogenesis of follicular cell derived thyroid cancers. Int J Surg, 8, 186-93. https://doi.org/10.1016/j.ijsu.2010.01.005
  23. Pouladi N, Kouhsari SM, Feizi MH, Gavgani RR, Azarfam P (2013). Overlapping region of p53/wrap53 transcripts: mutational analysis and sequence similarity with microRNA-4732-5p. Asian Pac J Cancer Prev, 14, 3503-7. https://doi.org/10.7314/APJCP.2013.14.6.3503
  24. Pouladi N, Kouhsari SM, Feizi MH, et al (2014). Lack of association of intron 3 16 bp polymorphism of TP53 with breast cancer among Iranian-Azeri patients. Asian Pac J Cancer Prev, 15, 2631-4. https://doi.org/10.7314/APJCP.2014.15.6.2631
  25. Radha RK, P V, B K (2014). Histopathology and prognostic indices of carcinoma breast with special reference to p53 marker. J Clin Diagn Res, 7, 4-8.
  26. Sedaie Bonab A, Pouladi N, Hosseinpourfeizi MA, et al (2014). Single-strand conformational polymorphism analysis of a common single nucleotide variation in WRAP53 gene, rs2287499, and evaluating its association in relation to breast cancer risk and prognosis among Iranian-Azeri population. Med Oncol, 31, 168 https://doi.org/10.1007/s12032-014-0168-4
  27. Shin MK, Kim JW (2014). Clinicopathologic and diagnostic significance of p53 protein expression in papillary thyroid carcinoma. Asian Pac J Cancer Prev, 15, 2341-4. https://doi.org/10.7314/APJCP.2014.15.5.2341
  28. Sipos JA, Mazzaferri EL (2010). Thyroid cancer epidemiology and prognostic variables. Clinical Oncology, 22, 395-404. https://doi.org/10.1016/j.clon.2010.05.004
  29. Stegh AH (2012). Targeting the P53 signaling pathway in cancer therapy - The promises, challenges, and perils. Expert Opin Ther Targets, 16, 67-83. https://doi.org/10.1517/14728222.2011.643299
  30. Surekha D, Sailaja K, Rao DN, et al (2011). Codon 72 and G13964C intron 6 polymorphisms of TP53 in relation to development and progression of breast cancer in India. Asian Pac J Cancer Prev, 12, 1893-8.
  31. Trifa F, Karray-Chouayekh S, Mabrouk I, et al (2010). Haplotype analysis of P53 polymorphisms: Arg72Pro, Ins16bp and G13964C inTunisian patients with familial or sporadic breast cancer. Cancer Epidemiol, 34, 184-88. https://doi.org/10.1016/j.canep.2010.02.007
  32. Varley JM, McGown G, Thorncroft M, et al (2001). Significance of intron 6 sequence variations in the TP53 gene in Li-Fraumeni syndrome. Cancer Genet Cytogenet, 129, 85-7. https://doi.org/10.1016/S0165-4608(01)00428-9
  33. Walsh T, Casadei S, Coats KH, et al (2006). Spectrum of mutations in BRCA1, BRCA2, CHEK2, and TP53 in families at high risk of breast cancer. J Am Med Association, https://doi.org/10.1001/jama.295.12.1379