Association between the TP53 Arg72Pro Polymorphisms and Gastric Cancer Risk: An Updated Meta-Analysis and Re-Analysis of Systematic Meta-Analyses

Abstract

Background: A latest Meta-analysis on TP53 Arg72Pro polymorphism with gastric cancer (GC) risk was published in 2015 including 20 literatures, while our study included 43 studies. Moreover, the results of previously published original studies were inconsistent and the credibility of the significant correlation between the statistical results has been ignored. Therefore, an updated Meta-analysis was conducted to further explore these associations. Objective: To explore whether these two gene polymorphisms are related to the risk, clinical manifestations, and pathological features of GC. Methods: We searched several Chinese and English databases. The crude odds ratio (OR) with 95% confidence interval (CI) was used to evaluate the correlation. In addition, false positive reporting probability (FPRP), bayesian false discovery probability (BFDP), and Venice criteria were used to assess the reliability of statistically significant correlation. Results: Overall, the TP53 Arg72Pro polymorphism was related to a significantly increased GC risk (AP vs. AA: OR = 1.12, 95% CI = 1.02 - 1.24; PP + AP vs. AA: OR = 1.12, 95% CI = 1.02 - 1.24; P vs. A: OR = 1.07, 95% CI = 1.00 - 1.15). However, after excluding the low quality and Hardy–Weinberg Disequilibrium (HWD) studies, significant changes were found on the TP53 Arg72Pro polymorphism with GC risk in Caucasians (PP vs. AA: OR = 1.48, 95% CI = 1.01 - 2.16) and non-gastric cancer control groups (PP vs. AP + AA: OR = 1.33, 95% CI = 1.07 - 1.64)). However, the above significant results were considered unreliable after being adjusted with Bayesian error detection probability (BFDP) and false positive reporting probability (FPRP). These unreliable results were confirmed again, and no new reliable results were found in the further sensitivity analysis (only studies that met the quality assessment criteria). Conclusions: After considering the quality of the study and the reliability of the results, this Meta-analysis showed that TP53 codon 72 polymorphisms had no significant correlation with GC risk. Because of various confounding factors, the result that these polymorphisms increase GC risk is more likely to be a false positive result.