Background and Aims: The MDM2 SNP309 polymorphism has been suggested as translating increased intracellular MDM2 levels and limits the cellular availability of functional p53. Thus, the aim of this study was to determine whether the MDM2 SNP309 polymorphism and MDM2 expression are associated with clinicopathological outcome and gastric cancer risk.
Methods: This cross-sectional study identified the MDM2 SNP309 polymorphism in a total of 68 patients by using Taq Man SNPs Genotyping assay. Immunohistochemistry was performed to evaluate MDM2 expression levels among patients with chronic gastritis, precancerous lesions, and gastric cancer. Logistic regression was used to estimate associations between polymorphisms, MDM2 expression, clinicopathological outcomes, and gastric cancer risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by multivariate Cox proportional hazards regression modelling, to determine the strength of any association with outcome.
Results:There was a significant link between the MDM2 SNP309 G/G homozygous polymorphism and MDM2 expression, and gastric cancer risk (OR=1.57, 95% CI=1.39–2.03, p=0.039). MDM2 expression was also suggested to be associated with gastric cancer risk. Poor clinicopathological outcome of gastric cancer indicated an association with MDM2 expression, including tumor location in the upper gastric region (OR=1.48, 95% CI=1.25–3.54, p=0.037), undifferentiated type (OR=2.47, 95% CI=1.38–4.14, p=0.016), presence of lymphatic invasion (OR=1.96, 95% CI=1.22–3.19, p=0.014), and unresectable tumor (OR=3.39, 95% CI=1.61–4.94 p=0.017).
Conclusion:Our study indicates an association between the MDM2 SNP309 G/G homozygous polymorphism, MDM2 protein expression, and clinicopathological outcome. Understanding genetic polymorphisms and expression of MDM2 may help explain gastric cancer risk in Thai populations.