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Carcinogenesis Advance Access published online on April 4, 2008
Carcinogenesis, doi:10.1093/carcin/bgn090
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© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

MDM2 and p53 Polymorphisms are Associated with the Development of Hepatocellular Carcinoma in Patients with Chronic Hepatitis B Virus Infection

Young Joon Yoon1,3,{dagger}, Hye Young Chang2,3,{dagger}, Sang Hoon Ahn1,2,3, Ja Kyung Kim1,3, Yong Kwang Park3,4, Dae Ryong Kang5, Jun Yong Park1,3, Sung Min Myoung2,3, Do Young Kim1,2,3, Chae Yoon Chon1,2,3 and Kwang-Hyub Han1,2,3,*

1 Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
2 Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
3 Liver Cirrhosis Clinical Research Center, Seoul, Korea
4 Brain Korea 21 Project for Medical Science, Yonsei University, Seoul, Korea
5 Clinical Trial Center, Yonsei University Health System, Seoul, Korea

* To whom correspondence should be addressed. Tel.: +82 2 2228 1949; Fax: +82 2 393 6884; E-mail: gihankhys{at}yuhs.ac

A single nucleotide polymorphism (SNP) in the promoter region of MDM2, SNP 309, is associated with hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus infection. The effect of p53 codon 72 polymorphism Arg72Pro on HCC risk remains inconsistent. This study evaluated the association of MDM2 and p53 polymorphisms with the presence and early onset of HCC in Korean patients with chronic hepatitis B virus (HBV) infection. In total, 583 consecutive patients with chronic HBV infection were classified according to the presence (n = 287) or absence (n = 296) of HCC. The MDM2 SNP 309 and p53 Arg72Pro were genotyped using restriction fragment length polymorphism method. The MDM2 G/G and p53 Pro/Pro genotypes were more frequent in HCC group than in non-HCC group (P < 0.001 and P = 0.004, respectively). Multivariate analysis for the presence of HCC revealed that the odds ratio (OR) for MDM2 G/G over T/T was 4.89 (P < 0.001), and that of p53 Pro/Pro over Arg/Arg was 3.03 (P = 0.006). Combined, MDM2 G/G and p53 Pro/Pro had a synergistic effect on HCC risk, with an OR of 20.78 (P < 0.001). The mean age of tumor onset in patients with MDM2 G/G genotype was 50.9 years, compared to 55.1 with T/T genotype (P = 0.018), and that with p53 Pro/Pro was 49.7 compared to 52.9 with Arg/Arg (P = 0.040). Thus, MDM2 SNP309 and p53 Arg72Pro are associated with the early development of HCC in Korean patients with chronic HBV infection.

Key Words: Hepatocellular carcinoma • Hepatitis B virus • MDM2 • p53 • Single nucleotide polymorphism

{dagger} These authors contributed equally to this work

Received November 21, 2007; revised March 28, 2008; accepted March 31, 2008.


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