Association between p53 Pro72Arg polymorphism and prostate cancer risk: a meta-analysis

Lifeng Zhang,Ning Shao,Qianqian Yu,Lixin Hua,Yuanyuan Mi,Ninghan Feng

doi:10.1016/s1674-8301(11)60003-1

Lifeng Zhang, Ning Shao + Show 4 more

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https://doi.org/10.1016/s1674-8301(11)60003-1

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Abstract

The tumor suppressor gene p53 appears to be important in the development of many human cancers, such as prostate cancer. The association of p53 codon72 polymorphism with prostate cancer has been widely reported; however, the results are inconsistent. To derive a more precise estimation of this relationship, we performed an updated meta-analysis from 10 case-control studies. We conducted a search in the PubMed database without a language limitation, covering all papers published until July 2010. Risk ratios (RR) with 95%confidence intervals (CIs) were used to assess the strength of the association. Ten studies including 1,196 cases and 1,704 controls were selected. Overall, no significant differences of total prostate cancer risk and p53 codon polymorphism was found (Pro/Pro vs Arg/Arg, RR = 1.12, 95%CI=0.74-1.70, Pheterogeneity = 0.016, I2 = 55.8%; Pro/Pro+Pro/Arg vs Arg/Arg, RR = 1.05, 95%CI=1.00-1.11, Pheterogeneity = 0.077, I2 = 51.1%). In the stratified analysis by ethnicity, the same results were found. However, in the control subgroup, there was a modest decreased association between prostate cancer risk and population-based control subjects under the recessive genetic model (RR = 0.31, 95%CI=0.10-0.91, Pheterogeneity = 0.110, I2 =60.8%). This meta-analysis suggested that p53 codon Pro72Arg polymorphism could be weakly associated with prostate cancer risk.

Highlights

Prostate cancer (PCa) is the most commonly seen male malignancy and the second leading cause of cancer deaths in men in the United States, with estimated 192,000 new cases and 27,000 deaths in 2009[1]
Studies testing the association between p53 codon Pro72Arg polymorphism and PCa were considered if all the following inclusion criteria were met: 1) the study assessed the correlation between global cancer and at least one of the polymorphisms cited above; 2) case-control studies; 3) control subjects were matched with case patients in age and gender; 4) only full-text manuscripts were included
For p53 codon Pro72Arg, we investigated the association between genetic variants and PCa risk in allelic contrast (Proallele vs Arg-allele), homozygote comparison (Pro/ Pro vs Arg/Arg), heterozygote comparison (Pro/Arg vs Arg/Arg), dominant genetic model (Pro/Pro+Pro/ Arg vs Arg/Arg) and recessive genetic model (Pro/Pro vs Pro/Arg+Arg/Arg)

Summary

Introduction

Prostate cancer (PCa) is the most commonly seen male malignancy and the second leading cause of cancer deaths in men in the United States, with estimated 192,000 new cases and 27,000 deaths in 2009[1]. PCa as a cause of death by cancer varies remarkably according to tumor grade, stage, age, and ethnic or racial groups. The p53 transcription factor is encoded by the TP53 gene, which is located on chromosome 17q13[3] and is one of the most commonly mutated genes in all types of human cancer. The p53 gene and its encoded protein play a central role in regulating cell cycle progression, DNA repair, cellular growth and apoptosis[4,5]; it can function as a tumor suppressor. Because p53 can suppuss tumor development, and control apoptosis and cell cycle checkpoint in cells under physiologicall stress, it is one of the most intensely studied human proteins and is often called the "guardian of the ge-

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