Association between <i>MDM2</i> gene <i>T309G</i> polymorphism and prostate cancer susceptibility: a meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

LIU Shuangtai ¹ , XI Shu ¹ , LI Fei ¹ ,  TAN Xiaolin ²

1. Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan 437101, P. R. China;
2. Administrative Office of President, Zhongnan Hospital of Wuhan University, Wuhan 437101, P. R. China;

Corresponding author：

TAN Xiaolin, Email: winterlin6@126.com

Keywords：

Murine double minute 2 (MDMZ); Prostate cancer; Gene polymorphism; Systematic review; Meta-analysis

DOI：

10.7507/1672-2531.202401025

Video：

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Objective To systematically review the relationship between T309G polymorphism of murine double minute 2 (MDM2) gene and susceptibility of prostate cancer. Methods The PubMed, Embase, WanFang Data, CNKI databases were electronically searched to collect case-control studies related to the objectives from inception to May, 2023. Two reviewers independently screened literature, extracted data and assessed the risk of bias of the included studies. Meta-analysis was then performed by using Stata 14.0 software. Results A total of 10 studies involving 5 781 patients and 5 477 healthy controls were included. The results of meta-analysis showed that the MDM2 gene T309G polymorphism was not associated with preeclampsia (allele model G vs. T: OR=0.89, 95%CI 0.77 to 1.04, P=0.13; homozygote model GG vs. TT: OR=0.86, 95%CI 0.64 to 1.16, P=0.32; heterozygote model TG vs. TT: OR=1.04, 95%CI 0.86 to 1.26, P=0.12; dominant model GG+TG vs. TT: OR=0.96, 95%CI 0.89 to 1.04, P=0.36; recessive model GG vs. TG+TT: OR=0.84, 95%CI 0.63 to 1.14, P=0.27). The results of subgroup analysis based on ethnicity and source of control were similar to the overall results. Sensitivity analysis showed that the results were robust. Conclusion Current evidence shows that the MDM2 gene T309G polymorphism is not associated with prostate cancer susceptibility. Due to the limited quality and quantity of the included studies, more high quality studies are needed to verify the above conclusion.

1.	Siegel RL, Miller KD, Fuchs HE, et al. Cancer statistics, 2022. CA Cancer J Clin, 2022, 72(1): 7-33.
2.	Watling CZ, Schmidt JA, Dunneram Y, et al. Risk of cancer in regular and low meat-eaters, fish-eaters, and vegetarians: a prospective analysis of UK Biobank participants. BMC Med, 2022, 20(1): 73.
3.	Kang DW, Fairey AS, Boulé NG, et al. A randomized trial of the effects of exercise on anxiety, fear of cancer progression and quality of life in prostate cancer patients on active surveillance. J Urol, 2022, 207(4): 814-822.
4.	Kim JS, Wilson RL, Taaffe DR, et al. Myokine expression and tumor-suppressive effect of serum after 12 wk of exercise in prostate cancer patients on ADT. Med Sci Sports Exerc, 2022, 54(2): 197-205.
5.	Lim JE, Huang J, Männistö S, et al. Hair dye use and prostate cancer risk: a prospective analysis in the Alpha-Tocopherol, Beta-Carotene cancer prevention study cohort. Cancer, 2022, 128(6): 1260-1266.
6.	Brookman-May SD, Campi R, Henríquez JDS, et al. Latest evidence on the impact of smoking, sports, and sexual activity as modifiable lifestyle risk factors for prostate cancer incidence, recurrence, and progression: a systematic review of the literature by the European association of urology section of oncological urology (ESOU). Eur Urol Focus, 2019, 5(5): 756-787.
7.	Sandhu S, Moore CM, Chiong E, et al. Prostate cancer. Lancet, 2021, 398(10305): 1075-1090.
8.	Rebello RJ, Oing C, Knudsen KE, et al. Prostate cancer. Nat Rev Dis Primers, 2021, 7(1): 9.
9.	Arap W, Pasqualini R, Costello JF. Prostate cancer progression and the epigenome. N Engl J Med, 2020, 383(23): 2287-2290.
10.	Kibel AS, Jin CH, Klim A, et al. Association between polymorphisms in cell cycle genes and advanced prostate carcinoma. Prostate, 2008, 68(11): 1179-1186.
11.	Mandal RK, Mittal RD. Are cell cycle and apoptosis genes associated with prostate cancer risk in North Indian population. Urol Oncol, 2012, 30(5): 555-561.
12.	Stoehr R, Hitzenbichler F, Kneitz B, et al. MDM2-SNP309 polymorphism in prostate cancer: no evidence for association with increased risk or histopathological tumour characteristics. Br J Cancer, 2008, 99(1): 78-82.
13.	Hirata H, Hinoda Y, Kikuno N, et al. Bcl2 -938C/A polymorphism carries increased risk of biochemical recurrence after radical prostatectomy. J Urol, 2009, 181(4): 1907-1912.
14.	Zeng X, Zhang Y, Kwong JS, et al. The methodological quality assessment tools for preclinical and clinical studies, systematic review and meta-analysis, and clinical practice guideline: a systematic review. J Evid Based Med, 2015, 8(1): 2-10.
15.	Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol, 2010, 25(9): 603-605.
16.	曾宪涛, 刘慧, 陈曦, 等. Meta分析系列之四: 观察性研究的质量评价工具. 中国循证心血管医学杂志, 2012, 4(4): 297-299.
17.	曾宪涛, Kwong JW, 田国祥, 等. Meta分析系列之二: Meta分析的软件. 中国循证心血管医学杂志, 2012, 4(2): 89-91.
18.	Weng H, Li S, Huang JY, et al. Androgen receptor gene polymorphisms and risk of prostate cancer: a meta-analysis. Sci Rep, 2017, 7: 40554.
19.	贺艺, 刘菊芳, 龚青, 等. 血管紧张素原基因T174M多态性与子痫前期发病风险相关性的Meta分析. 中国循证心血管医学杂志, 2017, 9(1): 10-13.
20.	徐文斌, 龚乘丙, 李尧, 等. p53 codon 72基因多态性与中国女性乳腺癌发生风险关系的系统评价与Meta分析. 医学新知, 2022, 32(1): 23-32.
21.	Zhou J, Wu H, Su QX, et al. Impacts of chemokine (C-X-C Motif) receptor 2 C1208T polymorphism on cancer susceptibility. J Immunol Res, 2021, 2021: 8727924.
22.	Xu B, Xu Z, Cheng G, et al. Association between polymorphisms of TP53 and MDM2 and prostate cancer risk in southern Chinese. Cancer Genet Cytogenet, 2010, 202(2): 76-81.
23.	Knappskog S, Trovik J, Marcickiewicz J, et al. SNP285C modulates oestrogen receptor/Sp1 binding to the MDM2 promoter and reduces the risk of endometrial but not prostatic cancer. Eur J Cancer, 2012, 48(13): 1988-1996.
24.	Gansmo LB, Knappskog S, Romundstad P, et al. Influence of MDM2 SNP309 and SNP285 status on the risk of cancer in the breast, prostate, lung and colon. Int J Cancer, 2015, 137(1): 96-103.
25.	Xue L, Han X, Liu R, et al. MDM2 and P53 polymorphisms contribute together to the risk and survival of prostate cancer. Oncotarget, 2016, 7(22): 31825-31831.
26.	慕玉东, 郝妮娜, 原荣, 等. MDM2 T309G 基因多态性与前列腺癌的相关性. 现代肿瘤医学, 2020, 28(4): 614-616.
27.	Sivonova MK, Jurecekova J, Kaplan P, et al. Association of MDM2 T309G (rs2279744) polymorphism and expression changes with risk of prostate cancer in the Slovak population. Anticancer Res, 2020, 40(11): 6257-6264.
28.	邓通, 蔡林, 陈征, 等. 1990年与2017年中国前列腺癌疾病负担分析. 医学新知, 2020, 30(4): 252-259.
29.	罗丽莎, 栾航航, 郑航, 等. 中国1990-2019年归因于吸烟的前列腺癌、膀胱癌和肾癌疾病负担研究. 中国循证医学杂志, 2022, 22(5): 530-536.
30.	Cahilly-Snyder L, Yang-Feng T, Francke U, et al. Molecular analysis and chromosomal mapping of amplified genes isolated from a transformed mouse 3T3 cell line. Somat Cell Mol Genet, 1987, 13(3): 235-244.
31.	Klein AM, de Queiroz RM, Venkatesh D, et al. The roles and regulation of MDM2 and MDMX: it is not just about p53. Genes Dev, 2021, 35(9-10): 575-601.
32.	Jones SN, Roe AE, Donehower LA, et al. Rescue of embryonic lethality in MDM2-deficient mice by absence of p53. Nature, 1995, 378(6553): 206-208.
33.	Duan Y, Ma G, Huang X, et al. The clustered, regularly interspaced, short palindromic repeats-associated endonuclease 9 (CRISPR/Cas9)-created MDM2 T309G mutation enhances vitreous-induced expression of MDM2 and proliferation and survival of cells. J Biol Chem, 2016, 291(31): 16339-16347.
34.	Yadav P, Masroor M, Tanwer K, et al. Clinical significance of TP53 (R72P) and MDM2 (T309G) polymorphisms in breast cancer patients. Clin Transl Oncol, 2016, 18(7): 728-734.
35.	Tian X, Wang B, Guo J, et al. The MDM2 T309G polymorphism and risk of lung cancer: an updated meta-analysis of 10 186 cases and 14 155 controls. Panminerva Med, 2016, 58(4): 341-348.

1. Siegel RL, Miller KD, Fuchs HE, et al. Cancer statistics, 2022. CA Cancer J Clin, 2022, 72(1): 7-33.
2. Watling CZ, Schmidt JA, Dunneram Y, et al. Risk of cancer in regular and low meat-eaters, fish-eaters, and vegetarians: a prospective analysis of UK Biobank participants. BMC Med, 2022, 20(1): 73.
3. Kang DW, Fairey AS, Boulé NG, et al. A randomized trial of the effects of exercise on anxiety, fear of cancer progression and quality of life in prostate cancer patients on active surveillance. J Urol, 2022, 207(4): 814-822.
4. Kim JS, Wilson RL, Taaffe DR, et al. Myokine expression and tumor-suppressive effect of serum after 12 wk of exercise in prostate cancer patients on ADT. Med Sci Sports Exerc, 2022, 54(2): 197-205.
5. Lim JE, Huang J, Männistö S, et al. Hair dye use and prostate cancer risk: a prospective analysis in the Alpha-Tocopherol, Beta-Carotene cancer prevention study cohort. Cancer, 2022, 128(6): 1260-1266.
6. Brookman-May SD, Campi R, Henríquez JDS, et al. Latest evidence on the impact of smoking, sports, and sexual activity as modifiable lifestyle risk factors for prostate cancer incidence, recurrence, and progression: a systematic review of the literature by the European association of urology section of oncological urology (ESOU). Eur Urol Focus, 2019, 5(5): 756-787.
7. Sandhu S, Moore CM, Chiong E, et al. Prostate cancer. Lancet, 2021, 398(10305): 1075-1090.
8. Rebello RJ, Oing C, Knudsen KE, et al. Prostate cancer. Nat Rev Dis Primers, 2021, 7(1): 9.
9. Arap W, Pasqualini R, Costello JF. Prostate cancer progression and the epigenome. N Engl J Med, 2020, 383(23): 2287-2290.
10. Kibel AS, Jin CH, Klim A, et al. Association between polymorphisms in cell cycle genes and advanced prostate carcinoma. Prostate, 2008, 68(11): 1179-1186.
11. Mandal RK, Mittal RD. Are cell cycle and apoptosis genes associated with prostate cancer risk in North Indian population. Urol Oncol, 2012, 30(5): 555-561.
12. Stoehr R, Hitzenbichler F, Kneitz B, et al. MDM2-SNP309 polymorphism in prostate cancer: no evidence for association with increased risk or histopathological tumour characteristics. Br J Cancer, 2008, 99(1): 78-82.
13. Hirata H, Hinoda Y, Kikuno N, et al. Bcl2 -938C/A polymorphism carries increased risk of biochemical recurrence after radical prostatectomy. J Urol, 2009, 181(4): 1907-1912.
14. Zeng X, Zhang Y, Kwong JS, et al. The methodological quality assessment tools for preclinical and clinical studies, systematic review and meta-analysis, and clinical practice guideline: a systematic review. J Evid Based Med, 2015, 8(1): 2-10.
15. Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol, 2010, 25(9): 603-605.
16. 曾宪涛, 刘慧, 陈曦, 等. Meta分析系列之四: 观察性研究的质量评价工具. 中国循证心血管医学杂志, 2012, 4(4): 297-299.
17. 曾宪涛, Kwong JW, 田国祥, 等. Meta分析系列之二: Meta分析的软件. 中国循证心血管医学杂志, 2012, 4(2): 89-91.
18. Weng H, Li S, Huang JY, et al. Androgen receptor gene polymorphisms and risk of prostate cancer: a meta-analysis. Sci Rep, 2017, 7: 40554.
19. 贺艺, 刘菊芳, 龚青, 等. 血管紧张素原基因T174M多态性与子痫前期发病风险相关性的Meta分析. 中国循证心血管医学杂志, 2017, 9(1): 10-13.
20. 徐文斌, 龚乘丙, 李尧, 等. p53 codon 72基因多态性与中国女性乳腺癌发生风险关系的系统评价与Meta分析. 医学新知, 2022, 32(1): 23-32.
21. Zhou J, Wu H, Su QX, et al. Impacts of chemokine (C-X-C Motif) receptor 2 C1208T polymorphism on cancer susceptibility. J Immunol Res, 2021, 2021: 8727924.
22. Xu B, Xu Z, Cheng G, et al. Association between polymorphisms of TP53 and MDM2 and prostate cancer risk in southern Chinese. Cancer Genet Cytogenet, 2010, 202(2): 76-81.
23. Knappskog S, Trovik J, Marcickiewicz J, et al. SNP285C modulates oestrogen receptor/Sp1 binding to the MDM2 promoter and reduces the risk of endometrial but not prostatic cancer. Eur J Cancer, 2012, 48(13): 1988-1996.
24. Gansmo LB, Knappskog S, Romundstad P, et al. Influence of MDM2 SNP309 and SNP285 status on the risk of cancer in the breast, prostate, lung and colon. Int J Cancer, 2015, 137(1): 96-103.
25. Xue L, Han X, Liu R, et al. MDM2 and P53 polymorphisms contribute together to the risk and survival of prostate cancer. Oncotarget, 2016, 7(22): 31825-31831.
26. 慕玉东, 郝妮娜, 原荣, 等. MDM2 T309G 基因多态性与前列腺癌的相关性. 现代肿瘤医学, 2020, 28(4): 614-616.
27. Sivonova MK, Jurecekova J, Kaplan P, et al. Association of MDM2 T309G (rs2279744) polymorphism and expression changes with risk of prostate cancer in the Slovak population. Anticancer Res, 2020, 40(11): 6257-6264.
28. 邓通, 蔡林, 陈征, 等. 1990年与2017年中国前列腺癌疾病负担分析. 医学新知, 2020, 30(4): 252-259.
29. 罗丽莎, 栾航航, 郑航, 等. 中国1990-2019年归因于吸烟的前列腺癌、膀胱癌和肾癌疾病负担研究. 中国循证医学杂志, 2022, 22(5): 530-536.
30. Cahilly-Snyder L, Yang-Feng T, Francke U, et al. Molecular analysis and chromosomal mapping of amplified genes isolated from a transformed mouse 3T3 cell line. Somat Cell Mol Genet, 1987, 13(3): 235-244.
31. Klein AM, de Queiroz RM, Venkatesh D, et al. The roles and regulation of MDM2 and MDMX: it is not just about p53. Genes Dev, 2021, 35(9-10): 575-601.
32. Jones SN, Roe AE, Donehower LA, et al. Rescue of embryonic lethality in MDM2-deficient mice by absence of p53. Nature, 1995, 378(6553): 206-208.
33. Duan Y, Ma G, Huang X, et al. The clustered, regularly interspaced, short palindromic repeats-associated endonuclease 9 (CRISPR/Cas9)-created MDM2 T309G mutation enhances vitreous-induced expression of MDM2 and proliferation and survival of cells. J Biol Chem, 2016, 291(31): 16339-16347.
34. Yadav P, Masroor M, Tanwer K, et al. Clinical significance of TP53 (R72P) and MDM2 (T309G) polymorphisms in breast cancer patients. Clin Transl Oncol, 2016, 18(7): 728-734.
35. Tian X, Wang B, Guo J, et al. The MDM2 T309G polymorphism and risk of lung cancer: an updated meta-analysis of 10 186 cases and 14 155 controls. Panminerva Med, 2016, 58(4): 341-348.

Chinese Journal of Evidence-Based Medicine

Latest ArticlesAssociation between MDM2 gene T309G polymorphism and prostate cancer susceptibility: a meta-analysis

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