Evaluating the association between p53 codon 72 Arg>pro polymorphism and risk of ovary cancer: a meta-analysis.

Mohammed A A Alqumber,Aditya K Panda,Shafiul Haque,Raju K Mandal,Naseem Akhter,Klaus Roemer

doi:10.1371/journal.pone.0094874

Abstract

AimAllelic polymorphism in codon 72 of the p53 tumor suppressor gene causes imbalance of p53 protein expression. Earlier studies have shown association between allelic polymorphism in codon 72 of the p53 gene with risk of ovary cancer (OC); however the results are inconclusive and conflicting. Therefore, we performed this meta-analysis to investigate the relation between p53 codon 72 Arg>Pro polymorphism and overall OC susceptibility.MethodsWe searched all eligible published studies based on the association between codon 72 of the p53 Arg>Pro polymorphism and risk of OC. Data were pooled together from individual studies and meta-analysis was performed. Pooled odds ratios (ORs) and 95% CI were calculated for allele contrast, homozygous, heterozygous, dominant and recessive genetic models.ResultsA total of twelve studies comprising of 993 OC cases and 1264 healthy controls were included in this meta-analysis. Overall, no significant association was detected for Pro allele carrier (Pro vs. Arg: p = 0.916; OR = 0.980, 95% CI = 0.677 to 1.419), homozygous (Pro/Pro vs. Arg/Arg: p = 0.419; OR = 0.731, 95% CI = 0.341 to 1.564), heterozygous (Arg/Pro vs. Arg/Arg: p = 0.248; OR = 1.237, 95% CI = 0.862 to 1.773), dominant (Pro/Pro+Arg/Pro vsArg/Arg: p = 0.699; OR = 1.089, 95% CI = 0.706 to 1.681), and recessive (Pro/Pro vs Arg/Arg+Arg/Pro: p = 0.329; OR = 0.754, 95% CI = 0.428 to 1.329) genetic models, respectively. Also, in the stratified analysis by ethnicity, no significant association of this polymorphism with risk of OC was found in the Caucasian population.ConclusionsThis meta-analysis suggested that codon 72 of the p53 Arg>Pro polymorphism may not significantly contribute in ovary cancer susceptibility. However, future large studies with gene-gene and gene-environment interactions are needed to validate these findings.

Highlights

Ovary cancer (OC) is the most common carcinoma among females with poor prognosis
The etiology of OC is still unclear and epidemiological studies have suggested that susceptibility to OC of an individual is influenced by several genetic factors [3]
This is a meta-analysis of published articles based on the association of p53 codon 72 Arg.Pro polymorphism and OC risk, so ethical approval was not required for this study

Summary

Introduction

Ovary cancer (OC) is the most common carcinoma among females with poor prognosis. It is the sixth leading cause of death among gynecological malignancies in females worldwide [1,2]. The p53 tumor suppressor gene (TP53 at 17p13), recognized as ‘‘the guardian of the genome’’, plays a significant role in the cell cycle arrest, senescence, DNA damage repair, regulates the cell cycle and requires loss of function mutations for tumor formation [4]. The p53 protein functions by interfering with central regulators of hypoxia which mediate angiogenesis, and eventually inhibit production of pro-angiogenic factors and endogenous angiogenesis inhibitors [5,6,7]. The major modes of TP53 inactivation are single-base substitutions and loss of alleles, with inactivation by viral or cellular proteins [10]

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