Association between MDM2‑SNP309 and p53R72P polymorphisms and the risk of bladder cancer in the Mongolian population

Avirmed,Shiirevnyamba; Wang,Bo‑Shen; Selenge,Baasansuren; Sanjaajamts,Amarsaikhan; Ganbat,Batmunkh; Erdenebileg,Ulziisaikhan; Purevsuren,Myagmarsuren; Jigjidsuren,Sarantsetseg; Batmunkh,Munkhbat; Lee,Yi‑Jang

doi:10.3892/mco.2017.1317

Association between MDM2‑SNP309 and p53R72P polymorphisms and the risk of bladder cancer in the Mongolian population

Authors:
- Shiirevnyamba Avirmed
- Bo‑Shen Wang
- Baasansuren Selenge
- Amarsaikhan Sanjaajamts
- Batmunkh Ganbat
- Ulziisaikhan Erdenebileg
- Myagmarsuren Purevsuren
- Sarantsetseg Jigjidsuren
- Munkhbat Batmunkh
- Yi‑Jang Lee
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Affiliations: Division of Urology, Department of Surgery, School of Medicine, Mongolian National University of Medical Sciences, Ulaanbaatar 14210, Mongolia, Department of Biomedical Imaging and Radiological Sciences, School of Biomedical Engineering, National Yang‑Ming University, Taipei 112, Taiwan, Department of Clinical Laboratory, First Central Hospital of Mongolia, Ulaanbaatar 210648, Mongolia, Science Technology Center, Mongolian National University of Medical Sciences, Ulaanbaatar 14210, Mongolia
Published online on: July 13, 2017 https://doi.org/10.3892/mco.2017.1317
Pages: 412-420

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Abstract

The current study aims to investigate whether MDM2‑SNP309 and p53R72P polymorphisms were associated with the risk of bladder cancer in Mongolian populations. These polymorphisms were evaluated in 79 controls and 63 bladder cancer cases using a PCR‑restriction fragment length polymorphism assay, followed by analysis using multivariate logistic regression model and the Kaplan‑Meier model to determine the odds ratio (OR) and age at onset of bladder cancer, respectively. The results revealed that the homozygous (G/G) genotype of MDM2‑SNP309 increased the risk of bladder cancer compared to the wild‑type (T/T) genotype [OR=1.629; 95% confidence interval (CI)=0.622‑4.266] among Mongolians. On the other hand, the homozygous (P/P) genotype of p53R72P tended to protect the population from bladder cancer compared with the wild‑type (R/R) genotype (OR=0.445; 95% CI=0.1727‑2.147). It also showed that G/G genotype of MDM2‑SNP309 increased the risk of bladder cancer when combined with the R/R genotype of p53R72P (OR=3.355; 95% CI=0.3914‑28.766). Stratification by smoking and history of chronic urinary tract diseases tended towards increasing the risk association of the G/G (OR=2.3704; 95% CI=0.4308‑3.044) and T/G genotypes (OR=5; 95% CI=0.8442‑30.4088) of MDM2‑SNP309 with bladder cancer, respectively. The protective role of P/P of p53R72P remained following stratification. MDM2‑SNP309 and p53R72P were not involved in early age onset of bladder cancer in Mongolian patients. Taken together, MDM2‑SNP309 and p53R72P had no significant association with bladder cancer in Mongolian patients. The two SNPs were also not able to predict early age at onset of bladder cancer.

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1	Ploeg M, Aben KK and Kiemeney LA: The present and future burden of urinary bladder cancer in the world. World J Urol. 27:289–293. 2009. View Article : Google Scholar : PubMed/NCBI
2	Sandagdorj T, Sanjaajamts E, Tudev U, Oyunchimeg D, Ochir C and Roder D: Cancer incidence and mortality in Mongolia-national registry data. Asian Pac J Cancer Prev. 11:1509–1514. 2010.PubMed/NCBI
3	Bolortuyaa B, Bayarmaa E and Galtsog L: Bladder cancer is diagnosed by pathology. Mongolian Med Sci. 2:12–15. 2010.
4	La Vecchia C and Airoldi L: Human bladder cancer: Epidemiological, pathological and mechanistic aspects. IARC Sci Publ. 1–157. 1999.
5	Burger M, Catto JW, Dalbagni G, Grossman HB, Herr H, Karakiewicz P, Kassouf W, Kiemeney LA, La Vecchia C, Shariat S and Lotan Y: Epidemiology and risk factors of urothelial bladder cancer. Eur Urol. 63:234–241. 2013. View Article : Google Scholar : PubMed/NCBI
6	Bond GL and Levine AJ: A single nucleotide polymorphism in the p53 pathway interacts with gender, environmental stresses and tumor genetics to influence cancer in humans. Oncogene. 26:1317–1323. 2007. View Article : Google Scholar : PubMed/NCBI
7	Hollstein M, Sidransky D, Vogelstein B and Harris CC: p53 mutations in human cancers. Science. 253:49–53. 1991. View Article : Google Scholar : PubMed/NCBI
8	Hrstka R, Coates PJ and Vojtesek B: Polymorphisms in p53 and the p53 pathway: Roles in cancer susceptibility and response to treatment. J Cell Mol Med. 13:440–453. 2009. View Article : Google Scholar : PubMed/NCBI
9	Pietsch EC, Humbey O and Murphy ME: Polymorphisms in the p53 pathway. Oncogene. 25:1602–1611. 2006. View Article : Google Scholar : PubMed/NCBI
10	Thomas M, Kalita A, Labrecque S, Pim D, Banks L and Matlashewski G: Two polymorphic variants of wild-type p53 differ biochemically and biologically. Mol Cell Biol. 19:1092–1100. 1999. View Article : Google Scholar : PubMed/NCBI
11	Xu T, Xu ZC, Zou Q, Yu B and Huang XE: P53 Arg72Pro polymorphism and bladder cancer risk-meta-analysis evidence for a link in Asians but not Caucasians. Asian Pac J Cancer Prev. 13:2349–2354. 2012. View Article : Google Scholar : PubMed/NCBI
12	Yang Z, Nie S, Zhu H, Wu X, Jia S, Luo Y and Tang W: Association of p53 Arg72Pro polymorphism with bladder cancer: A meta-analysis. Gene. 512:408–413. 2013. View Article : Google Scholar : PubMed/NCBI
13	Bond GL, Hu W, Bond EE, Robins H, Lutzker SG, Arva NC, Bargonetti J, Bartel F, Taubert H, Wuerl P, et al: A single nucleotide polymorphism in the MDM2 promoter attenuates the p53 tumor suppressor pathway and accelerates tumor formation in humans. Cell. 119:591–602. 2004. View Article : Google Scholar : PubMed/NCBI
14	Freedman DA and Levine AJ: Regulation of the p53 protein by the MDM2 oncoprotein-thirty-eighth G.H.A. Clowes Memorial Award Lecture. Cancer Res. 59:1–7. 1999.PubMed/NCBI
15	Knappskog S and Lønning PE: Effects of the MDM2 promoter SNP285 and SNP309 on Sp1 transcription factor binding and cancer risk. Transcription. 2:207–210. 2011. View Article : Google Scholar : PubMed/NCBI
16	Hitzenbichler F, Stoehr CG, Rogenhofer M, Wieland WF, Ruemmele P, Hartmann A and Stoehr R: Mdm2 SNP309 G-variant is associated with invasive growth of human urinary bladder cancer. Pathobiology. 81:53–59. 2014. View Article : Google Scholar : PubMed/NCBI
17	Onat OE, Tez M, Ozçelik T and Törüner GA: MDM2 T309G polymorphism is associated with bladder cancer. Anticancer Res. 26:3473–3475. 2006.PubMed/NCBI
18	Sanchez-Carbayo M, Socci ND, Kirchoff T, Erill N, Offit K, Bochner BH and Cordon-Cardo C: A polymorphism in HDM2 (SNP309) associates with early onset in superficial tumors, TP53 mutations, and poor outcome in invasive bladder cancer. Clin Cancer Res. 13:3215–3220. 2007. View Article : Google Scholar : PubMed/NCBI
19	Horikawa Y, Nadaoka J, Saito M, Kumazawa T, Inoue T, Yuasa T, Tsuchiya N, Nishiyama H, Ogawa O and Habuchi T: Clinical implications of the MDM2 SNP309 and p53 Arg72Pro polymorphisms in transitional cell carcinoma of the bladder. Oncol Rep. 20:49–55. 2008.PubMed/NCBI
20	Leu JD, Wang CY, Tsai HY, Lin IF, Chen RC and Lee YJ: Involvement of p53 R72P polymorphism in the association of MDM2-SNP309 with breast cancer. Oncol Rep. 25:1755–1763. 2011.PubMed/NCBI
21	Janković S and Radosavljević V: Risk factors for bladder cancer. Tumori. 93:4–12. 2007.PubMed/NCBI
22	Srivastava P, Jaiswal PK, Singh V and Mittal RD: Role of p53 gene polymorphism and bladder cancer predisposition in northern India. Cancer Biomark. 8:21–28. 2010–2011. View Article : Google Scholar
23	Hosen MB, Salam MA, Islam MF, Hossain A, Hawlader MZ and Kabir Y: Association of TP53 gene polymorphisms with susceptibility of bladder cancer in Bangladeshi population. Tumour Biol. 36:6369–6374. 2015. View Article : Google Scholar : PubMed/NCBI
24	Li DB, Wei X, Jiang LH, Wang Y and Xu F: Meta-analysis of epidemiological studies of association of P53 codon 72 polymorphism with bladder cancer. Genet Mol Res. 9:1599–1605. 2010. View Article : Google Scholar : PubMed/NCBI
25	Fajkovic H, Halpern JA, Cha EK, Bahadori A, Chromecki TF, Karakiewicz PI, Breinl E, Merseburger AS and Shariat SF: Impact of gender on bladder cancer incidence, staging, and prognosis. World J Urol. 29:457–463. 2011. View Article : Google Scholar : PubMed/NCBI