The Pro variant of the p53 codon 72 polymorphism is associated with hepatocellular carcinoma in Moroccan population
- 15 June 2007
- journal article
- Published by Wiley in Hepatology Research
- Vol. 37 (9) , 748-754
- https://doi.org/10.1111/j.1872-034x.2007.00126.x
Abstract
Aim: Codon 72 polymorphism of the p53 gene has been implicated in cancer risk, and it has been suggested that it may have an impact on the clinical outcome of the disease. Our objective was to evaluate the association between p53 polymorphism at codon 72 and hepatocellular carcinoma (HCC) in the Moroccan population.Methods: Genomic DNA was extracted from peripheral blood cells of 96 patients with HCC and 222 controls without HCC matched for age, gender and ethnicity. Codon 72 polymorphism of p53 was identified by PCR‐restriction fragment length polymorphism, confirmed by sequencing.Results: Patients with HCC had higher frequencies of Pro/Pro (13.5% vs. 6.3%, P < 0.02) than controls and consequently a 2.3‐fold increased risk of liver cancer development (odds ratio [OR], 2.304; 95% confidence interval [CI], 1.014–5.234). In addition, we found a significant association between the p53Arg72Pro polymorphism and the female gender in HCC. Men with Pro/Pro genotype had a 1.57‐fold increased risk for HCC, whereas the corresponding genotype in women had a 4.4‐fold increased risk of HCC (OR, 4.4; 95% CI, 1.18–16.42). No correlation between the polymorphism and HCC risk was found when comparing the hepatitis C virus (HCV)‐positive cases to HCV‐positive controls. However, HCV‐negative subjects and Pro/Pro genotype had a 3.31‐fold increased risk for HCC.Conclusion: These results provide evidence that p53 polymorphism at codon 72 is a modifier of hepatocarcinogenesis, especially in women and HCV‐negative subjects.Keywords
This publication has 40 references indexed in Scilit:
- Clinical features of hepatitis C virus‐related hepatocellular carcinoma and their association with α‐fetoprotein and protein induced by vitamin K absence or antagonist‐IILiver International, 2006
- p53 Arg72Pro polymorphism and risk of colorectal adenoma and cancerInternational Journal of Cancer, 2006
- A p53 polymorphism modifies the risk of hepatocellular carcinoma among non-carriers but not carriers of chronic hepatitis B virus infectionCancer Letters, 2005
- Codon 72 polymorphism of P53 gene does not affect the risk of cirrhosis and hepatocarcinoma in HCV-infected patientsCancer Letters, 2004
- The genetics and genomics of cancerNature Genetics, 2003
- The codon 72 polymorphic variants of p53 have markedly different apoptotic potentialNature Genetics, 2003
- The proline-rich domain of p53 is required for cooperation with anti-neoplastic agents to promote apoptosis of tumor cellsOncogene, 2002
- Hepatocellular carcinomaPublished by Elsevier ,2000
- Differential regulation of cellular target genes by p53 devoid of the PXXP motifs with impaired apoptotic activityOncogene, 1999
- Clinical Implications of the p53 Tumor-Suppressor GeneNew England Journal of Medicine, 1993