MDM2 –309 T>G Gene Polymorphism and Gastric Cancer Risk in Eastern Asian Population: A Meta-Analysis_Chinese Journal of Evidence-Based Medicine

Authors：

RAN HengQuan , ZHOU Yong , Chen Bo , YANG Ping ,  WU Xiaoting

Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, China;

Corresponding author：

WU Xiaoting, Email: wxt_0046@126.com

Keywords：

Gastric cancer; MDM2; Single nucleotide polymorphism; Meta-analysis; Case-control study

DOI：

10.7507/1672-2531.20130099

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective 　To investigate the correlation between MDM2 SNP309 and gastric cancer (GC) risk in Eastern Asian population.
Methods 　Two reviewers independently searched MEDLINE, EMbase and CBM (from January 1st, 1990 to October 23rd, 2012) for case-control studies on the correlation between MDM2 SNP309 and GC risk in Eastern Asian population. Two reviewers independently screen literature, extracted the data, and assessed the methodological quality. Then meta-analysis was performed using RevMan 5.0 software.
Results 　5 case-control studies were finally included involving 1 621 GC cases and 2 639 controls. The pooled results showed that the variant homozygote (309GG genotype) was significantly associated with an increased risk of GC as compared to wild-type homozygote (309TT genotype: OR=1.54, 95% CI 1.04 to 2.29, P=0.02). Nevertheless, no association was found in comparison of variant heterozygote (309TG genotype) between wild-homozygote (309TT genotype: OR=1.03, 95% CI 0.75 to 1.42, P=0.006). A significantly increased risk of GC was observed for the recessive model (GG vs. TT/TG: OR=1.49, 95% CI 1.20 to 1.84, P=0.07). While in the dominant model (GG/TG vs. TT), non-significant association was observed (OR=1.18, 95% CI 0.84 to 1.65, P=0.001).
Conclusion 　The MDM2 309GG may be significantly associated with an increased risk of GC among Eastern Asians.

Citation： RAN HengQuan,ZHOU Yong,Chen Bo,YANG Ping,WU Xiaoting. MDM2 –309 T>G Gene Polymorphism and Gastric Cancer Risk in Eastern Asian Population: A Meta-Analysis. Chinese Journal of Evidence-Based Medicine, 2013, 13(5): 560-563. doi: 10.7507/1672-2531.20130099 Copy

1.	Ahmedin J, Freddie B, Melissa M, et al. Global cancer statistics. Ca Cancer J Clin, 2011, 61(2): 69-90.
2.	Francesco G, Emma DF, Cornelia MvD, et al. A systematic review of meta-analyses on gene polymorphisms and gastric cancer risk. Current Genomics, 2008, 9(6): 361-374.
3.	Silva F, Carvalho F, Peixoto A, et al. MUC1 gene polymorphism in the gastric carcinogenesis pathway. Eur J Hum Genet, 2001, 9(7): 548- 552.
4.	Correa P, Schneider BG. Etiology of Gastric Cancer: What Is New? Cancer Epidem Biomar, 2005, 14(8): 1865-1868.
5.	Bose I, Ghosh B. The p53-MDM2 network: from oscillations to apoptosis. J Biosci, 2007, 32(5): 991-997.
6.	Colaluca IN, Tosoni D, Nuciforo P, et al. NUMB controls p53 tumour suppressor activity. Nature, 2008, 451(7174): 76-80.
7.	Daujat S, Neel H, Piette J. MDM2: life without p53. Trends in Genetics, 2001, 17(8): 459-464.
8.	Bond GL, Hu W, Bond EE, et al. A single nucleotide polymorphism in the MDM2 promoter attenuates the p53 tumor suppressor pathway and accelerates tumor formation in humans. Cell, 2004, 119(5): 591-602.
9.	Wan Y, Wu W, Yin Z, et al. MDM2 SNP309, gene-gene interaction, and tumor susceptibility: an updated meta-analysis. BMC cancer, 2011, 11(1): 208.
10.	Blok P, Craanen ME, Dekker W, et al. No evidence for functional inactivation of wild-type p53 protein by MDM2 overexpression in gastric carcinogenesis. J Patho, 1998, 186(1): 36-40.
11.	Well GA, Shea B, O’COnnell D, et al. the Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa Heath Research Institute.www.ohri. ca/ programs/ clinical_ epidemiology/ oxford asp(accessed Oct 20, 2012).
12.	Cao YY, Zhang XF, Guo W, et al. Association of the MDM2 polymorphisms with susceptibility of esophageal squamous cell carcinoma and that of gastric cardiac adenocarcinoma. Tumor, 2007, 27(8): 628-632.
13.	Wang XY, Yang J, Ho B, et al. Interaction of Helicobacter pylori with genetic variants in the MDM2 promoter, is associated with gastric cancer susceptibility in Chinese patients. Helicobacter, 2009, 14(5): 114-119.
14.	Yang M, Guo YL, Zhang XM, et al. Interaction of P53 Arg72Pro and MDM2 T309G polymorphisms and their associations with risk of gastric cardia cancer. Carcinogenesis, 2007, 28(9): 1996-2001.
15.	Ohmiya N, Taguchi A, Mabuchi N, et al. MDM2 promoter polymorphism is associated with both an increased susceptibility to gastric carcinoma and poor prognosis. J Clin Oncol, 2006, 24(27): 4434-4440.
16.	Cho YG, Cho BJ, Song JH, et al. No association of MDM2 T309G polymorphism with susceptibility to Korean gastric cancer patients. Neoplasma, 2008, 55(3): 256-260.
17.	Hirata H, Hinoda Y, Kikuno N, et al. MDM2 SNP309 polymorphism as risk factor for susceptibility and poor prognosis in renal cell carcinoma. Clin Cancer Res, 2007, 13(14): 4123-4129.
18.	Heidl G, Langhans P, Mellin W, et al. Adenocarcinomas of esophagus and cardia in comparison with gastric carcinoma. J Cancer Res Clin Oncol, 1993, 120(1-2): 95-99.
19.	Loeb LA, Loeb KR, Anderson JP. Multiple mutations and cancer. Proc Natl Acad Sci USA, 2003, 100(3): 776-781.
20.	Gao L, Nieters A, Brenner H. Cell proliferation-related genetic polymorphisms and gastric cancer risk: Systematic review and meta-analysis. Eur J Hum Genet, 2009, 17(12): 1658-1667.

1. Ahmedin J, Freddie B, Melissa M, et al. Global cancer statistics. Ca Cancer J Clin, 2011, 61(2): 69-90.
2. Francesco G, Emma DF, Cornelia MvD, et al. A systematic review of meta-analyses on gene polymorphisms and gastric cancer risk. Current Genomics, 2008, 9(6): 361-374.
3. Silva F, Carvalho F, Peixoto A, et al. MUC1 gene polymorphism in the gastric carcinogenesis pathway. Eur J Hum Genet, 2001, 9(7): 548- 552.
4. Correa P, Schneider BG. Etiology of Gastric Cancer: What Is New? Cancer Epidem Biomar, 2005, 14(8): 1865-1868.
5. Bose I, Ghosh B. The p53-MDM2 network: from oscillations to apoptosis. J Biosci, 2007, 32(5): 991-997.
6. Colaluca IN, Tosoni D, Nuciforo P, et al. NUMB controls p53 tumour suppressor activity. Nature, 2008, 451(7174): 76-80.
7. Daujat S, Neel H, Piette J. MDM2: life without p53. Trends in Genetics, 2001, 17(8): 459-464.
8. Bond GL, Hu W, Bond EE, et al. A single nucleotide polymorphism in the MDM2 promoter attenuates the p53 tumor suppressor pathway and accelerates tumor formation in humans. Cell, 2004, 119(5): 591-602.
9. Wan Y, Wu W, Yin Z, et al. MDM2 SNP309, gene-gene interaction, and tumor susceptibility: an updated meta-analysis. BMC cancer, 2011, 11(1): 208.
10. Blok P, Craanen ME, Dekker W, et al. No evidence for functional inactivation of wild-type p53 protein by MDM2 overexpression in gastric carcinogenesis. J Patho, 1998, 186(1): 36-40.
11. Well GA, Shea B, O’COnnell D, et al. the Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa Heath Research Institute.www.ohri. ca/ programs/ clinical_ epidemiology/ oxford asp(accessed Oct 20, 2012).
12. Cao YY, Zhang XF, Guo W, et al. Association of the MDM2 polymorphisms with susceptibility of esophageal squamous cell carcinoma and that of gastric cardiac adenocarcinoma. Tumor, 2007, 27(8): 628-632.
13. Wang XY, Yang J, Ho B, et al. Interaction of Helicobacter pylori with genetic variants in the MDM2 promoter, is associated with gastric cancer susceptibility in Chinese patients. Helicobacter, 2009, 14(5): 114-119.
14. Yang M, Guo YL, Zhang XM, et al. Interaction of P53 Arg72Pro and MDM2 T309G polymorphisms and their associations with risk of gastric cardia cancer. Carcinogenesis, 2007, 28(9): 1996-2001.
15. Ohmiya N, Taguchi A, Mabuchi N, et al. MDM2 promoter polymorphism is associated with both an increased susceptibility to gastric carcinoma and poor prognosis. J Clin Oncol, 2006, 24(27): 4434-4440.
16. Cho YG, Cho BJ, Song JH, et al. No association of MDM2 T309G polymorphism with susceptibility to Korean gastric cancer patients. Neoplasma, 2008, 55(3): 256-260.
17. Hirata H, Hinoda Y, Kikuno N, et al. MDM2 SNP309 polymorphism as risk factor for susceptibility and poor prognosis in renal cell carcinoma. Clin Cancer Res, 2007, 13(14): 4123-4129.
18. Heidl G, Langhans P, Mellin W, et al. Adenocarcinomas of esophagus and cardia in comparison with gastric carcinoma. J Cancer Res Clin Oncol, 1993, 120(1-2): 95-99.
19. Loeb LA, Loeb KR, Anderson JP. Multiple mutations and cancer. Proc Natl Acad Sci USA, 2003, 100(3): 776-781.
20. Gao L, Nieters A, Brenner H. Cell proliferation-related genetic polymorphisms and gastric cancer risk: Systematic review and meta-analysis. Eur J Hum Genet, 2009, 17(12): 1658-1667.

Chinese Journal of Evidence-Based Medicine

MDM2 –309 T>G Gene Polymorphism and Gastric Cancer Risk in Eastern Asian Population: A Meta-Analysis

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