Araştırma Makalesi
Yıl 2017,
, 644 - 651, 18.12.2017
Öz
Objective: Murine double minute 2 (MDM2) gene has a critical
role on regulation of p53 tumor suppressor pathway. MDM2 is a major negative
regulator of p53 function. MDM2
protein regulates p53 function through multiple independent pathways. The
present study aims to determine the frequency of MDM2 gene SNP309 (rs2279744)
polymorphism in the Turkish population.
Method: This
study included a total of 301 healthy Turkish individuals (159 females (53.0%)
and 141 males (47.0%) between 2014 and 2016. The frequency of T309G MDM2 rs2279744 polymorphism was
identified using restriction fragment length polymorphism-polymerase chain
reaction (RFLP-PCR) method.
Results: The mean
age of the study population was 49,80±16,4 years (51,97±15,98 years in men and
47,58±16,82 years in women). Genotype frequencies for MDM2 rs2279744 polymorphism were found to be 17.9% TT, 55.2% TG,
and 26.9% GG.
Conclusions: The present study provides information on the allele and genotype
frequency distribution of MDM2 gene
rs2279744 polymorphism in the Turkish population, which can be used as a
reference parameter for the investigation of susceptibility to various
disorders, particularly cancer.
Anahtar Kelimeler
Kaynakça
- 1. Freedman DA, Levine AJ. Nuclear export is required for degradation of endogenous p53 by MDM2 and human papillomavirus E6. Mol Cell Biol 1998; 18: 7288-93.
- 2. Schlott T, Reimer S, Jahns A, Ohlenbusch A, Ruschenburg I, Nagel H, et al. Point mutations and nucleotide insertions in the MDM2 zinc finger structure of human tumours. J Pathol 1997; 182: 54-61.
- 3. Giaccia AJ, Kastan MB. The complexity of p53 modulation: emerging patterns from divergent signals. Gene Dev 1998; 12: 2973-83.
- 4. Rocco JW, Sidransky D. p16(MTS-1/CDKN2/INK4a) in cancer progression. Exp Cell Res 2001; 264: 42-55.
- 5. Michael D, Oren M. The p53-Mdm2 module and the ubiquitin system. Semin Cancer Biol 2003; 13: 49-58.
- 6. Momand J, Wu HH, Dasgupta G. MDM2 - master regulator of the p53 tumor suppressor protein. Gene 2000; 242: 15-29.
- 7. Bond GL, Hu WW, Levine A. A single nucleotide polymorphism in the MDM2 gene: From a molecular and cellular explanation to clinical effect. Cancer Res 2005; 65: 5481-4.
- 8. Momand J, Zambetti GP, Olson DC, George D, Levine AJ. The Mdm-2 Oncogene Product Forms a Complex with the P53 Protein and Inhibits P53-Mediated Transactivation. Cell 1992; 69: 1237-45.
- 9. Zhang XM, Miao XP, Guo YL, Tan W, Zhou YF, Sun T, et al. Genetic polymorphisms in cell cycle regulatory genes MDM2 and TP53 are associated with susceptibility to lung cancer. Hum Mutat 2006; 27: 110-7.
- 10. Miller SA, Dykes DD, Polesky HF. A Simple Salting out Procedure for Extracting DNA from Human Nucleated Cells. Nucleic Acids Res 1988; 16: 1215.
- 11. Yilmaz M, Tas A, Kacan T, Sari M, Silig Y. Is there a relation between Murine double minute 2 T309G polymorphism and lung cancer risk in the Turkish population? Turk J Biochem 2017; 42: 123-9.
- 12. Ekmekci A, Konac E, I OH. Gen polimorfizmi ve kansere yatknlık. Marmara Medical Journal 2008; 21: 282-95.
- 13. Tuna G, Kucukhuseyin O, Arikan S, Saglam EK, Guler E, Cacina C, et al. Do CDKN2 p16 540 C > G, CDKN2 p16 580 C > T, and MDM2 SNP309 T > G Gene Variants Act on Colorectal Cancer Development or Progression? DNA Cell Biol 2013; 32: 400-8.
- 14. Petenkaya A, Bozkurt B, Akilli-Ozturk O, Kaya HS, Gur-Dedeoglu B, Yulug IG. Lack of association between the MDM2-SNP309 polymorphism and breast cancer risk. Anticancer Res 2006; 26: 4975-7.
- 15. Akkiz H, Sumbul AT, Bayram S, Bekar A, Akgollu E. MDM2 promoter polymorphism is associated with increased susceptibility to hepatocellular carcinoma in Turkish population. Cancer Epidemiol 2010; 34: 448-52.
- 16. Lind H, Zienolddiny S, Ekstrom PO, Skaug V, Haugen A. Association of a functional polymorphism in the promoter of the MDM2 gene with risk of nonsmall cell lung cancer. Int J Cancer 2006; 119: 718-21.
- 17. Walsh CS, Miller CW, Karlan BY, Koeffler HP. Association between a functional single nucleotide polyrnorphism in the MDM2 gene and sporadic endometrial cancer risk. Gynecol Oncol 2007; 104: 660-4.
- 18. Hong Y, Miao XP, Zhang XM, Ding F, Luo AP, Guo YL, et al. The role of P53 and MDM2 polymorphisms in the risk of esophageal squamous cell carcinoma. Cancer Res 2005; 65: 9582-7.
- 19. Onat OE, Tez M, Ozcelik T, Toruner GA. MDM2 T309G polymorphism is associated with bladder cancer. Anticancer Res 2006; 26: 3473-5.
- 20. Menin C, Scaini MC, De Salvo GL, Biscuola M, Quaggio A, Esposito G, et al. Association between MDM2-SNP309 and age at colorectal cancer diagnosis according to p53 mutation status. J Natl Cancer 2006; 98: 285-8.
- 21. Ohmiya N, Taguchi A, Mabuchi N, Itoh A, Hirooka Y, Niwa Y, et al. MDM2 promoter polymorphism is associated with both an increased susceptibility to gastric carcinoma and poor prognosis. J Clin Oncol 2006; 24: 4434-40.
- 22. Yoon YJ, Chang HY, Ahn SH, Kim JK, Park YK, Kang DR, et al. MDM2 and p53 polymorphisms are associated with the development of hepatocellular carcinoma in patients with chronic hepatitis B virus infection. Carcinogenesis 2008; 29: 1192-6.
- 23. Pan XL, Li YQ, Feng J, Wang XY, Hao B, Shi RH, et al. A functional polymorphism T309G in MDM2 gene promoter, intensified by Helicobacter pylori lipopolysaccharide, is associated with both an increased susceptibility and poor prognosis of gastric carcinoma in Chinese patients. Bmc Cancer 2013; 13.
- 24. Alhopuro P, Ylisaukko-oja SK, Koskinen WJ, Bono P, Arola J, Jarvinen HJ, et al. The MDM2 promoter polymorphism SNP309T -> G and the risk of uterine leiomyosarcoma, colorectal cancer, and squamous cell carcinoma of the head and neck. J Med Genet 2005; 42: 694-8.
- 25. Liu G, Cescon DW, Zhai R, Zhou W, Kulke MH, Ma C, et al. p53 Arg72Pro, MDM2 T309G and CCND1 G870A polymorphisms are not associated with susceptibility to esophageal adenocarcinoma. Dis Esophagus 2010; 23: 36-9.
- 26. Alazzouzi H, Suriano G, Guerra A, Plaja A, Espin E, Armengol M, et al. Tumour selection advantage of non-dominant negative P53 mutations in homozygotic MDM2-SNP309 colorectal cancer cells. J Med Genet 2007; 44: 75-80.
- 27. Talseth BA, Meldrum C, Suchy J, Kurzawski G, Lubinski J, Scott RJ. MDM2 SNP309 T > G alone or in combination with the TP53 R72P polymorphism does not appear to influence disease expression and age of diagnosis of colorectal cancer in HNPCC patients. Int J Cancer 2007; 120: 563-5.
- 28. Grochola LF, Muller TH, Bond GL, Taubert H, Udelnow A, Wurl P. MDM2 SNP309 Associates with accelerated pancreatic adenocarcinoma formation. Pancreas 2010; 39: 76-80.
- 29. Zimmer V, Hoblinger A, Mihalache F, Assmann G, Acalovschi M, Lammert F. Potential genotype-specific single nucleotide polymorphism interaction of common variation in p53 and its negative regulator mdm2 in cholangiocarcinoma susceptibility. Oncol Lett 2012; 4: 101-6.
- 30. Chaar I, Amara S, Khiari M, Ounissi D, Dhraif M, Ben Hamida AM, et al. Relationship Between MDM2 and p53 Alterations in Colorectal Cancer and Their Involvement and Prognostic Value in the Tunisian Population. Appl Immunohisto M M. 2013; 21: 228-36.
- 31. Cho YG, Choi BJ, Song JH, Kim CJ, Cao Z, Nam SW, et al. No association of MDM2 T309G polymorphism with susceptibility to Korean gastric cancer patients. Neoplasma 2008; 55: 256-60.
- 32. Sotamaa K, Liyanarachchi S, Mecklin JP, Jarvinen H, Aaltonen LA, Peltomaki P, et al. p53 codon 72 and MDM2 SNP309 polymorphisms and age of colorectal cancer onset in Lynch syndrome. Clin Cancer Res 2005; 11: 6840-4.
- 33. LI R, Zhang L, Liu Z, Hou C-p, Zhang Y-x, Wang Z-j, et al. Correlation of MDM2 gene polymorphisms and risk of esophageal squamous cell carcinoma in southwest shandong han nationality. Xinxiang Yi Xue Yuan Xue Bao 2011; 28: 437-42.
- 34. Ma J, Zhang JN, Ning T, Chen ZP, Xu CQ. Association of genetic polymorphisms in MDM2, PTEN and P53 with risk of esophageal squamous cell carcinoma. J Hum Genet 2012; 57: 261-4.
- 35. Tas A, Atabey M, Caglayan M, Bostanci EM, Bolukbasi SS, Topcu O, Silig Y. Investigation of the association between the MDM2 T309G polymorphism and gastric cancer. Biomedical Reports 2017 (doi.org/10.3892/br.2017.978).
Yıl 2017,
, 644 - 651, 18.12.2017
Öz
Amaç: Murine double
minute 2 (MDM2) geni p53 tümör
süpressör yolağının düzenlenmesinde kritik bir role sahiptir. MDM2, p53
fonksiyonunda büyük bir negatif regülatördür. MDM2 proteini birbirinden
bağımsız birçok yolla p53 fonksiyonunu düzenler. Bu çalışmada bir Türk Populasyonunda MDM2 geni SNP309 (rs2279744) polimorfizm
sıklığının belirlenmesi amaçlanmıştır.
Yöntem: Bu
çalışmada, MDM2 rs2279744 polimorfizm sıklığı toplam 301 (kadın: 159, % 53,0 ve
erkek: 141, % 47,0) Türk sağlıklı bireyde incelendi. T309G MDM2 rs2279744
polimorfizim sıklığı 301 sağlıklı kontrolde RFLP-PCR metoduyla belirlendi.
Bulgular: Çalışma grubunun yaş ortalaması 49,80±16,4 yıl
(erkek, 51,97±15,98; kadın, 47,58±16,82) idi. MDM2 rs2279744 polimorfizmine ait gözlenen genotip frekansları %
17.9 TT, % 55.1 TG ve %26.9 GG olarak tespit edildi.
Sonuç: Bu
çalışma, Türk toplumunda MDM2 geni
rs2279744 polimorfizminin allel ve genotip frekans dağılımları hakkında bilgi
vermektedir. Bu allel ve genotip dağılımları kanser başta olmak üzere birçok
hastalığa yatkınlığın araştırılmasında referans parametre olacaktır.
Anahtar Kelimeler
Kaynakça
- 1. Freedman DA, Levine AJ. Nuclear export is required for degradation of endogenous p53 by MDM2 and human papillomavirus E6. Mol Cell Biol 1998; 18: 7288-93.
- 2. Schlott T, Reimer S, Jahns A, Ohlenbusch A, Ruschenburg I, Nagel H, et al. Point mutations and nucleotide insertions in the MDM2 zinc finger structure of human tumours. J Pathol 1997; 182: 54-61.
- 3. Giaccia AJ, Kastan MB. The complexity of p53 modulation: emerging patterns from divergent signals. Gene Dev 1998; 12: 2973-83.
- 4. Rocco JW, Sidransky D. p16(MTS-1/CDKN2/INK4a) in cancer progression. Exp Cell Res 2001; 264: 42-55.
- 5. Michael D, Oren M. The p53-Mdm2 module and the ubiquitin system. Semin Cancer Biol 2003; 13: 49-58.
- 6. Momand J, Wu HH, Dasgupta G. MDM2 - master regulator of the p53 tumor suppressor protein. Gene 2000; 242: 15-29.
- 7. Bond GL, Hu WW, Levine A. A single nucleotide polymorphism in the MDM2 gene: From a molecular and cellular explanation to clinical effect. Cancer Res 2005; 65: 5481-4.
- 8. Momand J, Zambetti GP, Olson DC, George D, Levine AJ. The Mdm-2 Oncogene Product Forms a Complex with the P53 Protein and Inhibits P53-Mediated Transactivation. Cell 1992; 69: 1237-45.
- 9. Zhang XM, Miao XP, Guo YL, Tan W, Zhou YF, Sun T, et al. Genetic polymorphisms in cell cycle regulatory genes MDM2 and TP53 are associated with susceptibility to lung cancer. Hum Mutat 2006; 27: 110-7.
- 10. Miller SA, Dykes DD, Polesky HF. A Simple Salting out Procedure for Extracting DNA from Human Nucleated Cells. Nucleic Acids Res 1988; 16: 1215.
- 11. Yilmaz M, Tas A, Kacan T, Sari M, Silig Y. Is there a relation between Murine double minute 2 T309G polymorphism and lung cancer risk in the Turkish population? Turk J Biochem 2017; 42: 123-9.
- 12. Ekmekci A, Konac E, I OH. Gen polimorfizmi ve kansere yatknlık. Marmara Medical Journal 2008; 21: 282-95.
- 13. Tuna G, Kucukhuseyin O, Arikan S, Saglam EK, Guler E, Cacina C, et al. Do CDKN2 p16 540 C > G, CDKN2 p16 580 C > T, and MDM2 SNP309 T > G Gene Variants Act on Colorectal Cancer Development or Progression? DNA Cell Biol 2013; 32: 400-8.
- 14. Petenkaya A, Bozkurt B, Akilli-Ozturk O, Kaya HS, Gur-Dedeoglu B, Yulug IG. Lack of association between the MDM2-SNP309 polymorphism and breast cancer risk. Anticancer Res 2006; 26: 4975-7.
- 15. Akkiz H, Sumbul AT, Bayram S, Bekar A, Akgollu E. MDM2 promoter polymorphism is associated with increased susceptibility to hepatocellular carcinoma in Turkish population. Cancer Epidemiol 2010; 34: 448-52.
- 16. Lind H, Zienolddiny S, Ekstrom PO, Skaug V, Haugen A. Association of a functional polymorphism in the promoter of the MDM2 gene with risk of nonsmall cell lung cancer. Int J Cancer 2006; 119: 718-21.
- 17. Walsh CS, Miller CW, Karlan BY, Koeffler HP. Association between a functional single nucleotide polyrnorphism in the MDM2 gene and sporadic endometrial cancer risk. Gynecol Oncol 2007; 104: 660-4.
- 18. Hong Y, Miao XP, Zhang XM, Ding F, Luo AP, Guo YL, et al. The role of P53 and MDM2 polymorphisms in the risk of esophageal squamous cell carcinoma. Cancer Res 2005; 65: 9582-7.
- 19. Onat OE, Tez M, Ozcelik T, Toruner GA. MDM2 T309G polymorphism is associated with bladder cancer. Anticancer Res 2006; 26: 3473-5.
- 20. Menin C, Scaini MC, De Salvo GL, Biscuola M, Quaggio A, Esposito G, et al. Association between MDM2-SNP309 and age at colorectal cancer diagnosis according to p53 mutation status. J Natl Cancer 2006; 98: 285-8.
- 21. Ohmiya N, Taguchi A, Mabuchi N, Itoh A, Hirooka Y, Niwa Y, et al. MDM2 promoter polymorphism is associated with both an increased susceptibility to gastric carcinoma and poor prognosis. J Clin Oncol 2006; 24: 4434-40.
- 22. Yoon YJ, Chang HY, Ahn SH, Kim JK, Park YK, Kang DR, et al. MDM2 and p53 polymorphisms are associated with the development of hepatocellular carcinoma in patients with chronic hepatitis B virus infection. Carcinogenesis 2008; 29: 1192-6.
- 23. Pan XL, Li YQ, Feng J, Wang XY, Hao B, Shi RH, et al. A functional polymorphism T309G in MDM2 gene promoter, intensified by Helicobacter pylori lipopolysaccharide, is associated with both an increased susceptibility and poor prognosis of gastric carcinoma in Chinese patients. Bmc Cancer 2013; 13.
- 24. Alhopuro P, Ylisaukko-oja SK, Koskinen WJ, Bono P, Arola J, Jarvinen HJ, et al. The MDM2 promoter polymorphism SNP309T -> G and the risk of uterine leiomyosarcoma, colorectal cancer, and squamous cell carcinoma of the head and neck. J Med Genet 2005; 42: 694-8.
- 25. Liu G, Cescon DW, Zhai R, Zhou W, Kulke MH, Ma C, et al. p53 Arg72Pro, MDM2 T309G and CCND1 G870A polymorphisms are not associated with susceptibility to esophageal adenocarcinoma. Dis Esophagus 2010; 23: 36-9.
- 26. Alazzouzi H, Suriano G, Guerra A, Plaja A, Espin E, Armengol M, et al. Tumour selection advantage of non-dominant negative P53 mutations in homozygotic MDM2-SNP309 colorectal cancer cells. J Med Genet 2007; 44: 75-80.
- 27. Talseth BA, Meldrum C, Suchy J, Kurzawski G, Lubinski J, Scott RJ. MDM2 SNP309 T > G alone or in combination with the TP53 R72P polymorphism does not appear to influence disease expression and age of diagnosis of colorectal cancer in HNPCC patients. Int J Cancer 2007; 120: 563-5.
- 28. Grochola LF, Muller TH, Bond GL, Taubert H, Udelnow A, Wurl P. MDM2 SNP309 Associates with accelerated pancreatic adenocarcinoma formation. Pancreas 2010; 39: 76-80.
- 29. Zimmer V, Hoblinger A, Mihalache F, Assmann G, Acalovschi M, Lammert F. Potential genotype-specific single nucleotide polymorphism interaction of common variation in p53 and its negative regulator mdm2 in cholangiocarcinoma susceptibility. Oncol Lett 2012; 4: 101-6.
- 30. Chaar I, Amara S, Khiari M, Ounissi D, Dhraif M, Ben Hamida AM, et al. Relationship Between MDM2 and p53 Alterations in Colorectal Cancer and Their Involvement and Prognostic Value in the Tunisian Population. Appl Immunohisto M M. 2013; 21: 228-36.
- 31. Cho YG, Choi BJ, Song JH, Kim CJ, Cao Z, Nam SW, et al. No association of MDM2 T309G polymorphism with susceptibility to Korean gastric cancer patients. Neoplasma 2008; 55: 256-60.
- 32. Sotamaa K, Liyanarachchi S, Mecklin JP, Jarvinen H, Aaltonen LA, Peltomaki P, et al. p53 codon 72 and MDM2 SNP309 polymorphisms and age of colorectal cancer onset in Lynch syndrome. Clin Cancer Res 2005; 11: 6840-4.
- 33. LI R, Zhang L, Liu Z, Hou C-p, Zhang Y-x, Wang Z-j, et al. Correlation of MDM2 gene polymorphisms and risk of esophageal squamous cell carcinoma in southwest shandong han nationality. Xinxiang Yi Xue Yuan Xue Bao 2011; 28: 437-42.
- 34. Ma J, Zhang JN, Ning T, Chen ZP, Xu CQ. Association of genetic polymorphisms in MDM2, PTEN and P53 with risk of esophageal squamous cell carcinoma. J Hum Genet 2012; 57: 261-4.
- 35. Tas A, Atabey M, Caglayan M, Bostanci EM, Bolukbasi SS, Topcu O, Silig Y. Investigation of the association between the MDM2 T309G polymorphism and gastric cancer. Biomedical Reports 2017 (doi.org/10.3892/br.2017.978).
Toplam 35 adet kaynakça vardır.
Ayrıntılar
| Konular | Sağlık Kurumları Yönetimi |
|---|---|
| Bölüm | Basic Science Research Makaleler |
| Yazarlar | |
| Yayımlanma Tarihi | 18 Aralık 2017 |
| Kabul Tarihi | 4 Aralık 2017 |
| Yayımlandığı Sayı | Yıl 2017 |