Combined effects of p53 and MDM2 polymorphisms on susceptibility and surgical prognosis in hepatitis B virus-related hepatocellular carcinoma.

Published on Jan 1, 2013in Protein & Cell10.164
· DOI :10.1007/S13238-012-2067-9
Yun Yang6
Estimated H-index: 6
('SMMU': Second Military Medical University),
Tian Xia8
Estimated H-index: 8
(CAS: Chinese Academy of Sciences)
+ 6 AuthorsWeiping Zhou49
Estimated H-index: 49
('SMMU': Second Military Medical University)
Sources
Abstract
The p53 signaling pathway works as a potent barrier to tumor progression. Two single nucleotide polymorphisms (SNPs) in the gene loci of p53 pathway, p53 codon 72 Arg72Pro and MDM2 SNP309 (T > G), have been shown to cause perturbation of p53 function, but the effect of the two SNPs on the risk of hepatocellular carcinoma (HCC) remains inconsistent. This study investigated the influence of combined p53 Arg72Pro and MDM2 SNP309 on the risk of developing HCC in patients with chronic hepatitis B virus infection, and evaluated the significance of the two combined SNPs on patient prognosis. In total, 350 HCC patients, 230 non-HCC patients, and 96 healthy controls were genotyped for the p53 Arg72Pro and MDM2 SNP309. The combined p53 Pro/Pro and MDM2 G/G genotype was significantly associated with HCC risk (P = 0.047). Multivariate analysis indicated that combined p53 Pro/Pro and MDM2 G/G genotype was an independent factor affecting recurrence and survival (P < 0.05). Patients with combined p53 Pro/Pro and MDM2 G/G genotypes had a poorer prognosis than other genotypes, P < 0.01 for both disease-free survival (DFS) and overall survival (OS). DFS and OS rates also differed significantly between Barcelona Clinic Liver Cancer (BCLC) stage A patients with combined p53 Pro/Pro and MDM2 G/G and other genotypes (P < 0.05). Thus, the combined p53 Pro/Pro and MDM2 G/G genotype is associated with increased risk of developing HCC and is an independent adverse prognostic indicator in early stage HCC.
📖 Papers frequently viewed together
107 Citations
21 Citations
48.6k Citations
References42
Newest
#1Cristina BosettiH-Index: 102
#2Federica TuratiH-Index: 31
Last. Carlo La Vecchia (University of Milan)H-Index: 135
view all 3 authors...
Primary liver cancer (namely hepatocellular carcinoma, HCC) is worldwide the fifth most common cancer in men and the seventh one in women, and it represents the third most frequent cause of cancer death. HCC rates are particularly high in eastern/south-eastern Asia and in Africa, intermediate in Southern Europe, and low in most high-income countries. Persistent infections by HBV or HCV are the main recognized risk factors for HCC. Aflatoxin exposure is also an important risk factor for HCC devel...
366 CitationsSource
#1Jean-Charles Nault (French Institute of Health and Medical Research)H-Index: 39
: Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) are two leading causes of cancer death in the world. Liver carcinogenesis is driven by genetic alterations in combination with viral and environmental factors. β-catenin and P53 mutations represent the two main genetic alterations described in HCC, and P53 and KRAS mutations in CC, but rare genetic alterations could be particularly valuable if they constitute drug-able targets (such as PIK3CA or EGFR mutations). Recent progress using g...
136 CitationsSource
#1Robert J. Clifford (NIH: National Institutes of Health)H-Index: 29
#2Jinghui ZhangH-Index: 86
Last. Kenneth H. Buetow (NIH: National Institutes of Health)H-Index: 81
view all 21 authors...
Primary liver cancer is the third most common cause of cancer-related death worldwide, with a rising incidence in Western countries. Little is known about the genetic etiology of this disease. To identify genetic factors associated with hepatocellular carcinoma (HCC) and liver cirrhosis (LC), we conducted a comprehensive, genome-wide variation analysis in a population of unrelated Asian individuals. Copy number variation (CNV) and single nucleotide polymorphisms (SNPs) were assayed in peripheral...
108 CitationsSource
#1Wojciech Blonski (UPenn: University of Pennsylvania)H-Index: 18
#2David KotlyarH-Index: 10
Last. Kimberly A. FordeH-Index: 26
view all 3 authors...
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and represents an international public health concern as one of the most deadly cancers worldwide. The main etiology of HCC is chronic infection with hepatitis B and hepatitis C viruses. However, there are other important factors that contribute to the international burden of HCC. Among these are obesity, diabetes, non-alcoholic steatohepatitis and dietary exposures. Emerging evidence suggests that the etiology of many ca...
128 CitationsSource
#1Lukasz Filipp Grochola (Ludwig Institute for Cancer Research)H-Index: 8
#2Jorge Zeron-MedinaH-Index: 7
Last. Gareth L. Bond (University of Oxford)H-Index: 25
view all 4 authors...
The p53 tumor suppressor pathway is central both in reducing cancer frequency in vertebrates and in mediating the response of commonly used cancer therapies. This article aims to summarize and discuss a large body of evidence suggesting that the p53 pathway harbors functional inherited single-nucleotide polymorphisms (SNPs) that affect p53 signaling in cells, resulting in differences in cancer risk and clinical outcome in humans. The insights gained through these studies into how the functional ...
72 CitationsSource
#1Mang Xiao (SRRSH: Sir Run Run Shaw Hospital)H-Index: 6
#2Lei Zhang (SRRSH: Sir Run Run Shaw Hospital)H-Index: 4
Last. Yuehui Liu (NCU: Nanchang University)H-Index: 4
view all 7 authors...
Background The tumor suppressor TP53 and its negative regulator MDM2 play crucial roles in carcinogenesis. Previous case-control studies also revealed TP53 72Arg>Pro and MDM2 309T>G polymorphisms contribute to the risk of common cancers. However, the relationship between these two functional polymorphisms and nasopharyngeal carcinoma (NPC) susceptibility has not been explored.
28 CitationsSource
#1Christine Neuveut (Pasteur Institute)H-Index: 26
#2Yu Wei (Pasteur Institute)H-Index: 20
Last. Marie Annick Buendia (Pasteur Institute)H-Index: 25
view all 3 authors...
The hepatitis B virus (HBV) is a small enveloped DNA virus, which primarily infects hepatocytes and causes acute and persistent liver disease. Epidemiological studies have provided overwhelming evidence for a causal role of chronic HBV infection in the development of hepatocellular carcinoma, but the molecular mechanisms underlying virally-induced tumourigenesis remain largely debated. In the absence of a dominant oncogene encoded by the HBV genome, indirect roles have been proposed, including i...
295 CitationsSource
#1Jyh-Der LeuH-Index: 3
#2I-Feng LinH-Index: 3
Last. Yi-Jang LeeH-Index: 20
view all 6 authors...
CONCLUSION: Current data suggest that the association between MDM2-SNP309 GG genotype and HCC is not significant, while the risk may be enhanced in patients infected by hepatitis virus in Taiwan.
20 CitationsSource
#1Giuseppe ToffoliH-Index: 46
#2Paola BiasonH-Index: 13
Last. Massimo SerraH-Index: 65
view all 12 authors...
Purpose: The germ-line polymorphisms TP53 Arg72Pro and MDM2 SNP309 T>G are risk factors for tumor development and affect response to chemotherapy and survival in several cancers, but their prognostic and predictive value in patients with high-grade osteosarcomas is not yet defined. The purpose of this study was to investigate the effect of the TP53 Arg72Pro and the MDM2 SNP309 on the risk of osteosarcoma development and survival. Experimental Design: The relative risk to develop osteosarcomas an...
58 CitationsSource
#1David W. Cescon (U of T: University of Toronto)H-Index: 19
Last. Geoffrey LiuH-Index: 78
view all 17 authors...
Purpose: This study aimed to evaluate the prognostic significance of two functional single nucleotide polymorphisms (SNP) in the p53 pathway ( p53 Arg72Pro and MDM2 T309G ) in patients with esophageal cancer, and to determine the importance of histologic subtype in the SNP-outcome relationships. Experimental Design: A cohort of 371 patients with esophageal carcinoma enrolled in Boston, USA from 1999 to 2004 were genotyped for the p53 and MDM2 SNPs. Associations between genotypes and overall surv...
37 CitationsSource
Cited By24
Newest
#1Mingxue Yu (SYSU: Sun Yat-sen University)
#2Wenli Xu (SYSU: Sun Yat-sen University)
Last. Yutian Chong (SYSU: Sun Yat-sen University)H-Index: 7
view all 9 authors...
Hepatocellular carcinoma (HCC) is a common cancer and the leading cause is persistent hepatitis B virus (HBV) infection. We aimed to identify some core genes and pathways for HBV-related HCC. Gene expression profiles of GSE62232, GSE121248, and GSE94660 were available from Gene Expression Omnibus (GEO). The GSE62232 and GSE121248 profiles were the analysis datasets and GSE94660 was the validation dataset. The GEO2R online tool and Venn diagram software were applied to analyze commonly differenti...
3 CitationsSource
#1Chi Zhang (Xida: Guangxi University)H-Index: 2
#2Zhuo-Miao Ye (Xida: Guangxi University)H-Index: 2
Last. Li MengH-Index: 1
view all 8 authors...
Abstract Background Single nucleotide polymorphisms (SNPs) have been inconsistently associated with hepatocellular carcinoma (HCC) risk. This meta-analysis aimed to synthesize relevant data on SNPs associated with HCC in the Asian population. Methods Databases were searched to identify association studies of SNPs and HCC in Asians published through January 2019. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated based on 41 studies (13,167 patients with HCC and 15,886 n...
5 CitationsSource
#1Missiani Ochwoto (Kenya Medical Research Institute)
#2Colins O. Oduma (Egerton University)H-Index: 1
Last. Elijah M. Songok (Kenya Medical Research Institute)H-Index: 13
view all 10 authors...
Background: Human TP53 is the gatekeeper for generation of human cells and is highly conserved. Any alteration/mutation to TP53 adversely affects the regulatory function of the protein, potentially resulting in cancer. This study investigated mutations in codons 7 and 249 of TP53 , among patients with hepatocellular carcinoma (HCC) and chronic hepatitis B virus (HBV) infection at the Moi Teaching and Referral Hospital (MTRH), Eldoret, Kenya. Methods: In total, 33 HBV-positive patients attending ...
Source
Source
#1Zhen-Biao Zhang (Guangzhou University of Chinese Medicine)H-Index: 14
#2Dandan Luo (Guangzhou University of Chinese Medicine)H-Index: 12
Last. Jianping ChenH-Index: 15
view all 10 authors...
The biological activity of curcumin (CUR), a promising naturally occurring dietary compound for the treatment of hepatocellular carcinoma (HCC), was closely associated with its metabolite. Octahydrocurcumin (OHC) is the final hydrogenated metabolite of CUR and has been reported to have potential biological activities. However, difficulties in access have hampered its biological studies. In the current investigation, we designed an efficient synthesis method to produce OHC, and comparatively expl...
13 CitationsSource
#1Samy A. Azer (KSU: King Saud University)H-Index: 25
Human hepatocellular carcinoma (HCC) is the fifth most common cancer and is associated with poor prognosis worldwide. The molecular mechanisms underlying the pathogenesis of HCC have been an area of continuing interest, and recent studies using next generation sequencing (NGS) have revealed much regarding previously unsettled issues. Molecular studies using HCC samples have been mainly targeted with the aim to identify the fundamental mechanisms contributing to HCC and identify more effective tr...
12 CitationsSource
#1Weihai LiuH-Index: 2
#2Zhen-Biao Zhang (Guangzhou University of Chinese Medicine)H-Index: 14
Last. Hongying Cao (Guangzhou University of Chinese Medicine)H-Index: 1
view all 11 authors...
Curcumin (CUR), a widely used food additive, is derived mainly from Curcuma species that has been applied traditionally for the treatment of various diseases, including hepatocellular carcinoma (HCC). However, its poor systemic bioavailability hampers its clinical application, which may be related to its wide metabolism. Tetrahydrocurcumin (THC) is a major metabolite of CUR and has been reported to have multiple biologic activities. We investigated, for the first time, the efficacy and associate...
15 CitationsSource
Epidemiological studies have determined the associations between polymorphisms on the promoter of MDM2 (SNP309) and the codon 72 on exon 4 of p53 (p53 Arg72Pro) and the risk of hepatocellular carcinoma (HCC); however, the results were not always consistent. The aim of the present meta-analysis was to evaluate the overall associations between these 2 variants and HCC risk. The MEDLINE, Web of science, EMBASE, Cochrane Library, and CNKI databases were searched for eligibility studies and the data ...
3 CitationsSource
#1Bosheng He (Nantong University)H-Index: 3
#2Jianbing YinH-Index: 1
Last. Ying HeH-Index: 3
view all 8 authors...
AbstractObjective:We aimed to identify some pivotal genes and pathways for hepatocellular carcinoma (HCC) transformation from cirrhosis and explore potential targets for treatment of the disease.Methods:The GSE17548 microarray data were downloaded from Gene Expression Omnibus database, and 37 sample
18 CitationsSource
#1Wei Chang (Anhui Medical University)H-Index: 1
#2Wei He (Anhui Medical University)H-Index: 28
Last. Wei Wei (Anhui Medical University)H-Index: 73
view all 7 authors...
Abstract Celastrol , an active ingredient of Tripterygium Wilfordii , is a traditional Chinese medicinal herb, which has attracted interests for its potential anti-inflammatory and anti-cancer activities. The aim of this study was to evaluate the anti-tumor effect of Celastrol against diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) in rats and furthermore, to explore the underlying mechanism. Sprague-Dawley rats were intragastrically administered with DEN (10 mg/kg) for 6 days ev...
28 CitationsSource