A novel TP53 variant (rs78378222 A > C) in the polyadenylation signal is associated with increased cancer susceptibility: evidence from a meta-analysis.

Ying Wang,Tianjiao Ma,Zhen-Ya Shen,Xue-Song Wu,Jing He,Wei Lei

doi:10.18632/oncotarget.9056

Abstract

Polymorphisms in TP53 are involved in the progression of different types of cancer. A rare novel TP53 variant (rs78378222 A > C allele) was found via whole-genome sequencing in 2011. This variant was shown to significantly increase the risk of glioma, colorectal adenoma and prostate cancer. Functional analysis further revealed that this variant hindered TP53 expression and its downstream effect on apoptosis. Several studies have investigated the relationship between rs78378222 and cancer susceptibility. However, the results were not consistent. We conducted the first meta-analysis to give a more credible assessment on the association about this variant and cancer risk. Our meta-analysis included 34 studies consisting of 36599 cases and 91272 controls. These studies were mostly on the basis of high-grade data from Genome-wide association studies (GWASs). The results indicated that TP53 rs78378222 was significantly associated with an increased risk of overall cancer (AC vs. AA: OR = 1.511, 95% CI = 1.285–1.777). Furthermore, stratified analyses indicated that rs78378222 increased the risk of nervous system cancer, skin cancer and other cancer. To summarize, this meta-analysis suggested that rs78378222 C allele is a potent risk factor for overall cancer.

Highlights

Cancer has become an important challenge to public health
The results indicated that tumor protein 53 (TP53) rs78378222 was significantly associated with an increased risk of overall cancer (AC vs. AA: odds ratio (OR) = 1.511, 95% 95% confidence interval (CI) = 1.285–1.777)
15 publications were further removed for the following reasons:1 study was duplicated with study included in the meta-analysis; 5 were case only studies;7 had no adequate data to calculate OR and 95% CI; 2 were meta-analysis

Summary

Introduction

Cancer has become an important challenge to public health. High frequency of TP53 mutations was found in many types of human cancer [2]. Many researches focused on the p53 coding sequence (CDS) mutations, especially LiFraumeni mutations, which resulted in mutant p53 proteins that lacked normal functions and conferred oncogenic properties [6]. The function studies indicated that the p53 protein variant (72Pro/Pro) was likely to induce apoptosis with decreased kinetics, when compared with wild-type P53 (72Arg/Arg) [7]. Mouse models demonstrated that some genetic variations in TP53 enhancing oncogenic potential could not be attributed to defection of p53 CDS [8, 9]

Methods

Results

Conclusion