Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

Lack of Association of Intron 3 16 bp Polymorphism of TP53 with Breast Cancer among Iranian-Azeri Patients

  • Pouladi, Nasser (Department of Cellular and Molecular Biology, School of Biology, College of Sciences, University of Tehran) ;
  • Kouhsari, Shideh Montasser (Department of Cellular and Molecular Biology, School of Biology, College of Sciences, University of Tehran) ;
  • Feizi, Mohammadali Hosseinpour (Department of Biology, Faculty of Natural Science, University of Tabriz) ;
  • Dehghan, Roghayeh (Department of Biology, Faculty of Natural Science, University of Tabriz) ;
  • Azarfam, Parvin (Department of Biology, Faculty of Natural Science, University of Tabriz) ;
  • Farajzadeh, Davoud (Department of Biology, Faculty of Science, Azarbaijan Shahid Madani University)
  • Published : 2014.03.30
Download PDF
⟨ Previous Next ⟩

Abstract

Background: p53 gene is a well-known tumor suppressor gene that has several polymorphisms in both its exons and introns. It has been suggested that intron 3 16 bp duplication polymorphism may affect the gene function resulting in reduction or suppression of p53 anti tumor activity. In most case control studies a duplicated allele has been noticeably more frequent in cases rather than controls but there are also conflicting results. The aim of this study was to assess the association of intron 3 16 bp duplication polymorphism of p53 with breast cancer risk among Iranian-Azeri population. We also analyzed the clinicopathological information of patients as an epidemiological description of breast cancer in the north-west of Iran. Materials and Methods: This case-control study was performed on 221 breast cancer patients and 170 controls. Genomic DNA was extracted from peripheral blood samples and tumor tissues. p53 PIN3 genotype was determined using electrophoresis of PCR products on 8% non-denaturing polyacrylamide gels and silver staining. Results: In the control and case groups, respectively, 62.9% and 61.1% had no 16 bp insertion (A1A1 genotype), 7.1% and 7.7% had insertion in both p53 alleles (A2A2) and 30% and 31.2% were heterozygous (A1A2). There was no significant difference between genotype frequencies as well as allelic frequencies in two case and control groups. Conclusions: According to the result of the present study, the intron 3 16 bp duplication polymorphism of p53 could not be assessed as a marker of risk factor for predisposition to breast cancer in Azeri population. However, a high frequency of A2 allele (22.1%) in our population suggested that intron 3 16 bp duplication polymorphism may be a valuable marker for study in other cancers with well designed large groups.

Keywords

References

  1. Akkiprik M, Sonmez O, Gulluoglu BM, et al (2009). Analysis of p53 gene polymorphisms and protein over-expression in patients with breast cancer. Pathol Onco Res, 15, 359-68. https://doi.org/10.1007/s12253-008-9129-6
  2. Alawadi S, Ghabreau L, Alsaleh M, et al (2011). p53 gene polymorphisms and breast cancer risk in Arab women. Med Oncol, 28, 709-15. https://doi.org/10.1007/s12032-010-9505-4
  3. American Cancer Society (2013). Breast cancer facts, figures 2013-2014. Atlanta: American cancer society.
  4. Babu GR, Samari G, Cohen SP, et al (2011). Breast cancer screening among females in Iran and recommendations for improved practice: a review. Asian Pac J Cancer Prev, 12, 1647-55.
  5. Doosti A, Dehkordi P, Ghasemi, et al (2011). Association of the p53 codon 72 polymorphism with colorectal cancer in South West of Iran. Scientific Research and Essays, 51, 148-52.
  6. Faghani M, Ghasemi FM, Nikhbakht M, Salehi M (2011). TP53 PIN3 polymorphism associated with breast cancer risk in Iranian women. Indian J Cancer, 48, 298-302 https://doi.org/10.4103/0019-509X.84925
  7. Farnebo M, Bykov VJ, Wiman KG, et al (2010). The p53 tumor suppressor: a master regulator of diverse cellular processes and therapeutic target in cancer. Biochem Biophys Res Commun, 396, 85-9. https://doi.org/10.1016/j.bbrc.2010.02.152
  8. Forouzanfar MH, Foreman KJ, Delossantos AM, et al (2011). Breast and cervical cancer in 187 countries between 1980 and 2010: a systematic analysis. The Lancet, 378, 1461-84. https://doi.org/10.1016/S0140-6736(11)61351-2
  9. Gemignani F, Moreno V, Landi S, et al (2004). A TP53 polymorphism is associated with increased risk of colorectal cancer and with reduced levels of TP53 mRNA. Oncogene, 11, 1954-6.
  10. Guleria K, Sharma S, Manjari M, et al (2012). P.R72P, PIN3 Ins16bp polymorphisms of TP53 and CCR5$\Delta$32 in north Indian breast cancer patients. Asian Pac J Cancer Prev, 13, 3305-11. https://doi.org/10.7314/APJCP.2012.13.7.3305
  11. He XF, Su J, Zhang Y, et al (2011). Association between the p53 polymorphisms and breast cancer risk: meta-analysis based on case-control study. Breast Cancer Res Treat, 130, 517-29. https://doi.org/10.1007/s10549-011-1583-2
  12. Hofseth LJ, Hussain SP, Harris CC (2004). p53: 25 years after its discovery. Trends Pharmacol Sci, 25, 177-81. https://doi.org/10.1016/j.tips.2004.02.009
  13. Hu Z, Li X, Qu X, et al (2010). Intron 3 16 bp duplication polymorphism of TP53 contributes to cancer susceptibility: a meta-analysis. Carcinogenesis, 31, 643-7. https://doi.org/10.1093/carcin/bgq018
  14. Kazemi M, Salehi Z, Chakosari RJ (2009). TP53 codon 72 polymorphism and breast cancer in northern Iran. Oncol Res, 18, 25-30. https://doi.org/10.3727/096504009789745629
  15. Machado-Silva A, Perrier S, Bourdon JC (2010). p53 family members in cancer diagnosis and treatment. Seminars in Cancer Biology, 20, 57-62. https://doi.org/10.1016/j.semcancer.2010.02.005
  16. Marcel V, Tran PL, Sagne C, et al (2011). G-quadruplex structures in TP53 intron 3: role in alternative splicing and in production of p53 mRNA isoforms. Carcinogenesis, 32, 271-8. https://doi.org/10.1093/carcin/bgq253
  17. Martin AM, Weber BL (2000). Genetic and Hormonal Risk Factors in Breast Cancer. J Natl Cancer Inst, 92, 1126-35. https://doi.org/10.1093/jnci/92.14.1126
  18. Olden K, Freudenberg N, Dowd J, Shields AE (2011). Discovering how environmental exposures alter genes could lead to new treatments for chronic illnesses. Health Aff (Millwood), 30, 833-41 https://doi.org/10.1377/hlthaff.2011.0078
  19. Osorio A, Pollan M, Pita G, et al (2008). An evaluation of the polymorphisms Ins16bp and Arg72Pro in p53 as breast cancer risk modifiers in BRCA1 and BRCA2 mutation carriers. Br J Cancer, 99, 974-7. https://doi.org/10.1038/sj.bjc.6604624
  20. Pathy NB, Yip CH, Taib NA, et al (2011). Breast cancer in a multi-ethnic Asian setting: results from the Singapore- Malaysia hospital-based breast cancer registry. Breast, 20, 75-80.
  21. 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
  22. Roy AG, Sarkar B, Roy R, Rao V, Bandyopadhyay A (2012). Absence of p53 gene mutations in exons 5 - 7 among breast cancer patients of Bengalee Hindu caste females, West Bengal, India. Asian Pac J Cancer Prev, 13, 4477-9. https://doi.org/10.7314/APJCP.2012.13.9.4477
  23. Sagne C, Marcel V, Amadou A, et al (2013). A meta-analysis of cancer risk associated with the TP53 intron 3 duplication polymorphism (rs17878362): geographic and tumor-specific effects. Cell Death Dis, 4, 492. https://doi.org/10.1038/cddis.2013.24
  24. Salehi Z, Hadavi M (2012). Analysis of the codon 72 polymorphism of TP53 and human papillomavirus infection in Iranian patients with prostate cancer. J Med Virol, 84, 1423-7. https://doi.org/10.1002/jmv.23268
  25. 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
  26. Trifa F, Karray-Chouayekh S, Mabrouk I, et al (2010). Haplotype analysis of p53 polymorphisms: arg72Pro, Ins16bp and G13964C in tunisian patients with familial or sporadic breast cancer. Cancer Epidemiology, 34, 184-8. https://doi.org/10.1016/j.canep.2010.02.007
  27. Vijayaraman KP, Veluchamy M, Murugesan P, Shanmugiah KP, Kasi PD (2012). p53 exon 4 (codon 72) polymorphism and exon 7 (codon 249) mutation in breast cancer patients in southern region (Madurai) of Tamil Nadu. Asian Pac J Cancer Prev, 13, 511-6. https://doi.org/10.7314/APJCP.2012.13.2.511
  28. Wang-GohrkeS, Becher H, Kreienberg R, Runnebaum IB, Chang-Claude J (2002). Intron 3 16 bp duplication polymorphism of p53 is associated with an increased risk for breast cancer by the age of 50 years. Pharmacogenetics, 12, 269-72. https://doi.org/10.1097/00008571-200204000-00012
  29. Whibley C, Pharoah PD, Hollstein M (2009). p53 polymorphisms: cancer implications. Nature Reviews Cancer, 9, 95-107. https://doi.org/10.1038/nrc2584
  30. Wu D, Zhang Z, Chu H, et al (2013). Intron 3 sixteen base pairs duplication polymorphism of p53 contributes to breast cancer susceptibility: evidence from meta-analysis. PLoS One, 8, 61662. https://doi.org/10.1371/journal.pone.0061662
  31. Wu X, Zhao H, Amos CI, et al (2002). p53 Genotypes and haplotypes associated with lung cancer susceptibility and ethnicity. J Natl Cancer Inst, 94, 681-90. https://doi.org/10.1093/jnci/94.9.681

Cited by

  1. TP53 Polymorphisms in Sporadic North Indian Breast Cancer Patients vol.15, pp.16, 2014, https://doi.org/10.7314/APJCP.2014.15.16.6871
  2. Association of rs1219648 in FGFR2 and rs1042522 in TP53 with Premenopausal Breast Cancer in an Iranian Azeri Population vol.15, pp.18, 2014, https://doi.org/10.7314/APJCP.2014.15.18.7955
  3. Association of TP53 PIN3 polymorphism with breast cancer in Moroccan population vol.35, pp.12, 2014, https://doi.org/10.1007/s13277-014-2556-y
  4. No Evidence of Association of the Arg72Pro p53 Gene Polymorphism with Cancer Risk in the Saudi Population: a Meta-Analysis vol.16, pp.14, 2015, https://doi.org/10.7314/APJCP.2015.16.14.5663
  5. 14-bp Insertion/Deletion Polymorphism of the HLA-G gene in Breast Cancer among Women from North Western Iran vol.16, pp.14, 2015, https://doi.org/10.7314/APJCP.2015.16.14.6155
  6. The TP53 intron 6 G13964C Polymorphism and Risk of Thyroid and Breast Cancer Development in the Iranian Azeri Population vol.16, pp.7, 2015, https://doi.org/10.7314/APJCP.2015.16.7.3073
  7. Association between polymorphisms in TP53 and MDM2 genes and susceptibility to prostate cancer vol.13, pp.4, 2017, https://doi.org/10.3892/ol.2017.5739