Serum p53 gene polymorphisms and severity of hepatitis B or C-related chronic liver diseases in Taiwan

Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan, .
Hepatology International (Impact Factor: 1.78). 02/2011; 5(3):814-21. DOI: 10.1007/s12072-010-9248-5
Source: PubMed


Polymorphisms of p53 gene are known to play an important role in hepatocarcinogenesis. We aimed to investigate the impact of p53 polymorphisms on disease progression by evaluating their prevalence among chronic hepatitis B (CHB) or hepatitis C (CHC) patients with different stages of liver disease.
A total of 215 CHB, 108 CHC patients with different stages of liver disease and 49 healthy controls were consecutively enrolled. The codon 249 p53 mutations as well as codon 72 polymorphisms were assayed by molecular methods, and their prevalence among the enrolled subjects was evaluated.
All patients and controls had codon 249 wild-type sequences. Among codon 72 sequences, Pro/Pro allele frequency of Hepatitis B-related HCC (31.4%), cirrhosis (26.9%), HBV carriers (26.3%), hepatitis C-related cirrhosis (39.1%), and CHC patients (24%) were higher than that of healthy controls (18.4%). After adjustment for sex and age, codon 72 mutant and mixed type were associated with a higher likelihood of asymptomatic carrier state than those with wild type in CHB patients [odd ratio (OR): 2.53, 95% confidence interval (CI) 1.06-6.03, P = 0.037]. However, the prevalence of codon 72 mutant and mixed type were comparable with wild type among CHC patients with HCC (OR 0.70, 95% CI 0.28-1.72, P = 0.433).
Although serum 249(serine) p53 mutation is rarely found in Taiwanese patients, HBV carriers have a higher prevalence of codon 72 mutants than patients with much severe liver diseases or HCV infection, which implies that codon 72 mutants may affect at an earlier stage of HBV infection. Further studies are necessary to delineate the interactions of p53 mutations with HBV infection.

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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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