Polymorphisms in TP53, MDM2 Genes and Risk of Renal Cell Carcinoma in a Mongolian Population
DOI:
https://doi.org/10.24079/CAJMS.2025.01.002Keywords:
TP53, MDM2, renal cell carcinoma, Polymorphism, Mongolia, Case-controlAbstract
Objective: Renal cell carcinoma (RCC) is one of the most common malignancies of the kidney, with genetic factors playing a critical role in its development. Among the key genetic factors, TP53 and MDM2 gene polymorphisms have been implicated in cancer susceptibility, but their association with RCC remains unclear in different populations. This study evaluated the association of TP53 and MDM2 gene polymorphisms with RCC risk among Mongolian individuals. Method: In a hospital-based case-control study, 88 RCC cases and 88 matched controls were analyzed for TP53 and MDM2 variants using RFLP-PCR based genotyping. Results: The TP53 CG and CC genotypes and MDM2 TG and GG genotypes were not significantly associated with RCC risk when considered individually. However, individuals carrying the MDM2 GG and TP53 CC genotypes showed elevated RCC risk, although statistical significance was not reached. No strong interaction effects between genotypes and clinical risk factors such as smoking or urinary tract disease were observed. Conclusion: While TP53 and MDM2 polymorphisms showed trends toward association with RCC, larger studies are warranted to clarify their roles in genetic susceptibility within the Mongolian population.
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1. Coggan JL, Tan A, Kuzel TM. Renal Cancer. Cancer Consult: Expertise in Clinical Practice, Volume 1: Solid Tumors and Supportive Care. 2024;1:361-373. https://doi.org/10.1002/9781119823766.ch30
2. Avirmed S, Khuanbai Y, Sanjaajamts A, et al. Modifying Effect of Smoking on GSTM1 and NAT2 in Relation to the Risk of Bladder Cancer in Mongolian Population: A Case-Control Study. Asian Pac J Cancer Prev. 2021;22(8):2479-2485. https://doi.org/10.31557/APJCP.2021.22.8.2479
3. Bigham AW. Genetics of Human Origin and Evolution: High-Altitude Adaptations. Curr Opin Genet Dev. 2016;41:8. https://doi.org/10.1016/j.gde.2016.06.018
4. Dugee O, Lin Khor G, Lye MS, et al. Association of Major Dietary Patterns with Obesity Risk among Mongolian Men and Women. Asia Pac J Clin Nutr. 2009;18(3):433-440
5. Shuch B, Zhang J. Genetic Predisposition to Renal Cell Carcinoma: Implications for Counseling, Testing, Screening, and Management. J Clin Oncol. 2018;36(36):3560-3566. https://doi.org/10.1200/JCO.2018.79.2523
6. Flaherty KT, Fuchs CS, Colditz GA, et al. A prospective study of body mass index, hypertension, and smoking and the risk of renal cell carcinoma (United States). Cancer Causes Control. 2005;16(9):1099-1106. https://doi.org/10.1007/S10552-005-0349-8
7. Lew JQ, Chow WH, Hollenbeck AR, et al. Alcohol consumption and risk of renal cell cancer: The NIH-AARP diet and health study. Br J Cancer. 2011;104(3):537-541. https://doi.org/10.1038/sj.bjc.6606089
8. Bellocco R, Pasquali E, Rota M, et al. Alcohol drinking and risk of renal cell carcinoma: results of a meta-analysis. Ann Oncol. 2012;23(9):2235-2244. https://doi.org/10.1093/annonc/mds022
9. Jin X, Qiu T, Li L, et al. Pathophysiology of obesity and its associated diseases. Acta Pharm Sin B. 2023;13(6):2403. https://doi.org/10.1016/j.apsb.2023.01.012
10. Pengpid S, Peltzer K. Trends in concurrent tobacco use and heavy drinking among individuals 15 years and older in Mongolia. Sci Rep. 2022;12(1). http://dx.doi.org/10.1038/s41598-022-21094-7
11. Wang H, Guo M, Wei H, et al. Targeting p53 pathways: mechanisms, structures and advances in therapy. Signal Transduct Target Ther. 2023;8(1):1-35. https://doi.org/10.1038/s41392-023-01347-1
12. Zhu IY, Lloyd A, Critchley WR, et al. Structure and function of MDM2 and MDM4 in health and disease.
Biochem J. 2025;482(04):241-262. https://doi.org/10.1042/bcj20240757
13. Hernández Borrero LJ, El-Deiry WS. Tumor Suppressor p53: Biology, Signaling Pathways, and Therapeutic Targeting. Biochim Biophys Acta Rev Cancer. 2021;1876(1):188556. https://doi.org/10.1016/j.bbcan.2021.188556
14. Roos-Mattila M, Kallio P, Luck TJ, et al. Distinct molecular profiles and shared drug vulnerabilities in pancreatic metastases of renal cell carcinoma. Commun Biol. 2024;7(1):1355. https://doi.org/10.1038/s42003-024-07004-9
15. Clark PE. The role of VHL in clear-cell renal cell carcinoma and its relation to targeted therapy. Kidney Int. 2009;76(9):939. https://doi.org/10.1038/ki.2009.296
16. de Cubas AA, Rathmell WK. Epigenetic modifiers: activities in renal cell carcinoma. Nat Rev Urol. 2018;15(10):599. https://doi.org/10.1038/s41585-018-0052-7
17. González-Rodríguez P, Engskog-Vlachos P, Zhang H, SETD2 mutation in renal clear cell carcinoma suppress autophagy via regulation of ATG12. Cell Death Dis. 2020;11(1):1-15. https://doi.org/10.1038/s41419-020-2266-x
18. Kapur P, Rajaram S, Brugarolas J. The expanding role of BAP1 in clear cell renal cell carcinoma. Hum Pathol. 2022;133:22. https://doi.org/10.1016/j.humpath.2022.07.022
19. Bagnardi V, Rota M, Botteri E, et al. Alcohol consumption and site-specific cancer risk: A comprehensive dose-response meta-analysis. Br J Cancer. 2015;112(3):580-593. https://doi.org/10.1038/bjc.2014.579
20. Cui H, Du J, Xue H. The causal relationship between smoking, alcohol consumption, and renal clear cell carcinoma: a Mendelian randomization study. Front Genet. 2024;15:1391542. https://doi.org/10.3389/fgene.2024.1391542
21. Campi R, Rebez G, Klatte T, et al. Effect of smoking, hypertension and lifestyle factors on kidney cancer — perspectives for prevention and screening programmes. Nat Rev Urol. 2023;20(11):669-681. https://doi.org/10.1038/s41585-023-00781-8
22. MacLeod LC, Hotaling JM, Wright JL, et al. Risk Factors for Renal Cell Carcinoma in the Vitamin and Lifefstyle (VITAL) Study. J Urol. 2013;190(5):1657. https://doi.org/10.1016/j.juro.2013.04.130
23. Wan Y, Wu W, Yin Z. MDM2 SNP309, gene-gene interaction, and tumor susceptibility: an updated meta-analysis. BMC Cancer. 2011;11:208. https://doi.org/10.1186/1471-2407-11-208
24. Noon AP, Vlatković N, Polański R, et al. p53 and MDM2 in Renal Cell Carcinoma: Biomarkers for Disease Progression and Future Therapeutic Targets? Cancer. 2010;116(4):780. https://doi.org/10.1002/cncr.24841
25. Post SM, Quintás-Cardama A, Pant V, et al. A high-frequency regulatory polymorphism in the p53 pathway accelerates tumor development. Cancer Cell. 2010;18(3):220. https://doi.org/10.1016/j.ccr.2010.07.010
26. Swiatkowska A. p53 and Its Isoforms in Renal Cell Carcinoma Do They Matter Biomedicines. 2022;10(6):1330. https://doi.org/10.3390/biomedicines10061330
27. Noon AP, Vlatković N, Polański R, et al. p53 and MDM2 in Renal Cell Carcinoma: Biomarkers for Disease Progression and Future Therapeutic Targets? Cancer. 2010;116(4):780. https://doi.org/10.1002/cncr.24841
28. Suster D, Ronen S, Peterson JF, et al. MDM2 amplification and immunohistochemical expression in sarcomatoid renal cell carcinoma. Hum Pathol. 2019;87:28-36. https://doi.org/10.1016/j.humpath.2019.02.004
29. Chang SY, Chang WS, Shih HY, et al. Genetic Variations in MDM2 Gene Contribute to Renal Cell Carcinoma Susceptibility: A Genotype–Phenotype Correlation Study. Cancer. 2025;17(2):177. https://doi.org/10.3390/cancers17020177
30. Robles AI, Jen J, Harris CC. Clinical Outcomes of TP53 Mutations in Cancers. Cold Spring Harb Perspect Med. 2016;6(9):a026294. https://doi.org/10.1101/cshperspect.a026294
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