TP53 Codon 72 Polymorphism with Hepatocellular Carcinoma: A Meta-Analysis

Abstract

446OBJECTIVE: The association between codon 72 polymorphism of the tumour protein p53 (TP53) gene -which results in a missense mutation of arginine (R) to proline (P) -and susceptibility to hepatocellular carcinoma (HCC) is controversial. A metaanalysis was performed in order to define this relationship more precisely. METHODS: Published studies of TP53 codon 72 polymorphism and the risk of HCC were identified. Data were extracted, and summary odds ratios (OR) and 95% confidence intervals (95% CI) were calculated. Pooled ORs were determined for an additive model (R/R versus P/P), a dominant model ([R/R + R/P] versus P/P) and a recessive model (R/R versus [R/P + P/P]). RESULTS: The meta-analysis included seven case-control studies (total 1511 cases and 2165 controls). The risk of cancer was significantly decreased in the overall dominant model and the dominant model in Asian populations. A significantly decreased risk was found for all models in hospital-based but not population-based studies. There was no association between polymorphism and cancer risk when data were stratified according to hepatitis B or C virus infection status. CONCLUSION: The TP53 codon 72 polymorphism may be a risk factor for HCC. KEY WORDS: HEPATOCELLULAR CARCINOMA (HCC); TUMOUR PROTEIN P53 (TP53); CODON 72; POLYMORPHISM; META-ANALYSIS IntroductionHepatocellular carcinoma (HCC) accounts for 85 -90% of primary liver cancers, which are the fifth most common cancers worldwide. 1 The distribution of HCC varies among geographic regions and ethnic groups. 2 The incidence of this disease is increasing in developed countries in spite of considerable diagnostic and therapeutic progress. Tumour protein p53 is a tumour suppressor that plays an important role in cell cycle regulation and the maintenance of genome integrity. 9 TP53 mediates the cellular response to DNA damage via effects on gene transcription, DNA synthesis and repair, genomic plasticity and apoptosis. 10 Mutation of TP53 can result in uncontrolled cell proliferation and is associated with an increased risk of several cancers, including HCC. 11Several studies have investigated the association of TP53 polymorphisms with the risk of cancer.12 -14 The most studied polymorphism in the TP53 gene is a G>C replacement in exon 4, at codon 72. 15 This results in a mis-sense mutation of arginine (R) to proline (P) 16 and the production of a protein with different biological and biochemical characteristics. There are three possible distinct TP53 genotypes: homozygous for arginine (R/R); homozygous for proline (P/P); and heterozygous (R/P). Studies regarding the possible association of this polymorphism with HCC have shown inconclusive results, and most have included only small numbers of cases and controls. This meta-analysis was conducted in order to determine the effects of this polymorphism on the risk of HCC. Materials and methods IDENTIFICATION OF STUDIESA literature search was conducted in order to identify studies that examined the association of the TP53 codon 72 polymorphism with HCC. T...

P53 codon 72 Arg/Pro polymorphism and lung cancer risk in Asians: an updated meta-analysis

“…Mutations of the p53 gene may result in loss of its tumor suppressor function and thus contribute to the carcinogenesis and/or tumor progression. The polymorphism of p53 codon 72, a transversion of G to C (Arg to Pro), has been shown to be related to the risk of some malignant tumors [7–9]. It has been confirmed that the two polymorphic variants, Arg and Pro, of p53 codon 72 differ biochemically and biologically [10, 11].…”

TP53 and MDM2 Gene Polymorphisms, Gene-Gene Interaction, and Hepatocellular Carcinoma Risk: Evidence from an Updated Meta-Analysis

“…Six of these articles were excluded including 3 publications containing overlapping data [26]–[28], and 3 were meta-analyses [13], [17], [18]. Manual search of references cited in the published studies did not reveal any additional articles.…”

“…With respect to MDM2 SNP309 polymorphism, a meta-analysis by Ma et al [13] found that the MDM2 SNP309 polymorphism was associated with an increased HCC risk in Asians and Caucasians, however, they failed to include all eligible studies in the meta-analysis [14], [15], [16], which make their conclusions questionable. With respect to TP53 R72P polymorphism, two meta-analyses [17], [18] investigating the same hypothesis, quite similar in methods and performed almost at the same time, yielded different conclusions. Furthermore, the two previous meta-analyses did not cover all eligible studies.…”

Association Between MDM2 Promoter SNP309 T/G Polymorphism and Liver Cancer Risk - a Meta-analysis

“…Finally, gene-gene and gene-environmental factors interactions were not fully addressed in this meta-analysis for the lack of sufficient data. HBV, HCV and several gene polymorphisms, such as P53 codon72, GSTM1 and GSTT1, are associated with liver cancer, and there may be gene-gene or gene-environmental factors interactions (Wang et al, 2010, Ding et al, 2012. However, we could not perform gene-gene and gene-environmental analyses owing to the limited reported information on such associations in the included studies.…”