TITLE:
Association between the TP53 Arg72Pro Polymorphisms and Gastric Cancer Risk: An Updated Meta-Analysis and Re-Analysis of Systematic Meta-Analyses
AUTHORS:
Lili Huo, Yuwei Wang, Di Wang, Jingyi Chen, Changqing Yang, Xiaofeng He
KEYWORDS:
P53, Polymorphism, Gastric Cancer, Meta-Analysis, BFDP, FPRP
JOURNAL NAME:
Advances in Lung Cancer,
Vol.12 No.1,
March
31,
2023
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.