p53 codon 72 polymorphism is associated with susceptibility to hepatocellular carcinoma in the Turkish population: a case–control study

Department of Internal Medicine, Faculty of Medicine, Çukurova University, 01330 Adana, Turkey.
Molecular Biology Reports (Impact Factor: 1.96). 05/2011; 39(2):1639-47. DOI: 10.1007/s11033-011-0903-2
Source: PubMed

ABSTRACT The tumor suppressor p53 gene plays a crucial role in preventing carcinogenesis through its ability to induce cell cycle arrest and apoptosis following DNA damage and oncogene activation. A guanine (G)/cytosine (C) common single nucleotide polymorphism (SNP) at second position of codon 72 in exon 4 of p53 gene determines a arginine (Arg) to proline (Pro) (Arg72Pro) aminoacidic substitution within the proline-rich domain of p53 protein. Arg72 and Pro72 allele are different from a biochemical and biological point of view and many reports suggest that they can modulate individual cancer susceptibility. To determine the association of the p53 Arg72Pro polymorphism with the risk of hepatocellular carcinoma (HCC) development in a Turkish population, a hospital-based case-control study was designed consisting of 119 subjects with HCC and 119 cancer-free control subjects matched for age, gender, smoking and alcohol status. The genotype frequency of the p53 Arg72Pro polymorphism was determined by using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Our data shows that the Pro/Pro genotype of the p53 Arg72Pro polymorphism is associated with increased risk of HCC development in this Turkish population (OR = 3.20, 95% CI: 1.24-8.22, P = 0.02). Furthermore, according to stratified analysis, a significant association was observed between the homozygote Pro/Pro genotype and HCC risk in the subgroups of male gender (OR = 3.01, 95% CI: 1.14-7.97, P = 0.03) and patients with hepatitis B virus (HBV)-related HCC (OR = 4.04, 95% CI: 1.46-11.15, P = 0.007). Because our results suggest for the first time that the Pro/Pro homozygote of p53 Arg72Pro polymorphism may be a genetic susceptibility factor for HCC (especially in the male gender and HBV-infected patients) in the Turkish population, further independent studies are required to validate our findings in a larger series, as well as in patients of different ethnic origins.

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    ABSTRACT: Background: Previous studies on the association between the TP53 Arg72Pro polymorphism and hepatocellular carcinoma (HCC) risk obtained controversial findings. This study aimed to quantify the strength of the association by meta-analysis. Methods: We searched PubMed and Wangfang databases for published studies on the association between the TP53 Arg72Pro polymorphism and HCC risk, using the pooled odds ratio (OR) with its 95% confidence intervals (95% CI) for assessment. Results: 10 studies with a total of 2,026 cases and 2,733 controls were finally included into this meta-analysis. Overall, the TP53 Arg72Pro polymorphism was not associated with HCC risk (all P values greaterth HCC risk in Caucasians in three genetic models (For Pro versus Arg, OR = 1.20, 95%CI 1.03-1.41; For ProPro versus ArgArg, OR = 1.74, 95%CI 1.23-2.47; For ProPro versus ArgPro/ArgArg, OR = 1.85, 95%CI 1.33-2.57). However, there was no significant association between the TP53 Arg72Pro polymorphism and HCC risk in East Asians (all P values greater than 0.10). No evidence of publication bias was observed. Conclusion: Meta-analyses of available data suggest an obvious association between the TP53 Arg72Pro and HCC risk in Caucasians. However, the TP53 Arg72Pro polymorphism may have a race-specific effect on HCC risk and further studies are needed to elucidate this possible effect.
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    ABSTRACT: Background Hepatocellular carcinoma (HCC) is one of the most common malignant neoplasms worldwide. The p53 gene is frequently mutated in some histological subtypes of HCC. The role of p53 mutations and polymorphic variant of codon 72 in the prognosis of disease is still unclear. The p53 tumor suppressor gene Arg72Pro polymorphism has been associated with HCC. However, results were inconsistent. This meta-analysis was performed to estimate the association between p53 Arg72Pro polymorphism and HCC or HCC infected by HBV/HCV. Methods Electronic search of PubMed was conducted to select studies. Studies containing available genotype frequencies of Arg72Pro were chosen, and pooled odds ratio (OR) with 95 % confidence interval (CI) was used to assess the association. Results Ten published studies, including 1,371 HCC cases and 2,517 controls were identified. The overall results suggested that the variant genotypes were associated with the HCC risk (Pro/Pro vs. Pro/Arg + Arg/Arg: OR 1.355, 95 % CI 1.041–1.764, p = 0.024). In the stratified analysis, individuals with the Pro/Pro in the recessive model had increased risk of HCC (OR 1.927, 95 % CI 1.127–3.297, p = 0.017) in Caucasian. A symmetric funnel plot, the Begg’s test, was suggestive of the lack of publication bias. There was no association between the p53 codon 72 polymorphism and HBV/HCV-positive HCC. Conclusion This meta-analysis suggests that p53 condon 72 Pro/Progenotypes are associated with increased risk of HCC in Caucasian. To validate this association, further studies with larger participants worldwide are needed to examine the associations between this polymorphism and HCC.
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