The mouse double minute 2 polymorphism is associated with both decreased p53 expression and poor clinicopathological outcomes of gastric cancer.

Abstract

This study aimed to determine the mouse double minute 2 (MDM2) SNP309 polymorphism and to evaluate MDM2 and p53 expression and the association of MDM2 positivity in gastric cancer and clinicopathological outcomes. A total of 400 patients with chronic gastritis, precancerous lesions, and gastric cancer were used to identify the MDM2 SNP309 polymorphism by using the Taq Man SNP Genotyping assay. Immunohistochemistry was performed to evaluate MDM2 and p53 expression. The associations of polymorphisms, protein expression, clinicopathological outcomes, and gastric cancer risk were calculated by multivariate Cox proportional hazards regression model analysis and expressed by odds ratios (ORs) and 95% confidence intervals (CIs). The MDM2 SNP309 G/G homozygous polymorphism was significantly associated with expressed MDM2 in gastric cancer (OR = 1.57, 95% CI = 1.39-2.03, P = 0.039). Moreover, in gastric cancer, p53 was significantly decreased compared to MDM2 (P = 0.007). However, MDM2 and p53 expression were not significantly different among genotypes, and the G/G genotype can result in the altered protein expression of p53 in gastric cancer. Clinicopathological outcome was significantly associated 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). Our study indicated associations of the MDM2 SNP309 G/G homozygous polymorphism, MDM2 and p53 expression. Therefore, G/G-associated MDM2 revealed that P53 expression was decreased in gastric cancer and poor clinicopathological outcomes. Understanding the genetic polymorphisms and expression of MDM2 may help explain gastric cancer risk.