Association of Murine Double Minute 2 polymorphisms with gastric cancer: A systematic review with meta-analysis

Gastric cancer (GC) is the 5th most common type of cancer, with the 3rd highest mortality rate worldwide in both sexes. Murine double minute 2 (MDM2) protein is the major negative regulator of p53, and genetic polymorphisms in this gene have shown to be associated with several types of cancer. In the present study, a literature search was performed using PubMed and Scopus with the following key word combinations 'gastric cancer AND polymorphism AND MDM2'. Studies were carefully revised according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify eligible studies that matched the inclusion criteria. Statistical analysis was performed to assess the association between the different genetic polymorphisms and GC risk, by calculating the odds ratios (OR) and the confidence intervals (CI), with a 5% level of significance. A total of 11 manuscripts studied MDM2 polymorphisms in GC: rs937283 (n=1), rs3730485 (n=1) and rs2279744 (n=9). Both the rs937283 and rs3730485 reports showed an association with GC; however, there was only one study on each of these polymorphisms in the literature. A meta-analysis was performed for the rs2279744 polymorphism, of which studies showed a positive association between the G allele and risk of GC, either in the dominant model (OR=1.46; 95% CI 1.21-1.75; P<0.001) or recessive model (OR 1.65; 95% CI 1.45-1.87; P<0.001). In conclusion, genetic polymorphisms in MDM2 seemed to be associated with an increased risk of GC development, nevertheless, the number of studies were relatively low and the studied populations were primarily Chinese. The present meta-analysis emphasizes the need for additional studies in other populations to corroborate the association of these polymorphisms with GC.