Dataset Information

Effects of RAGE Gene Polymorphisms on the Risk and Progression of Hepatocellular Carcinoma.

ABSTRACT: Hepatocellular carcinoma (HCC) is a common malignancy of the liver, whose heterogeneous incidence reflects genetic variations among individuals in the main risk factors. The receptor for advanced glycosylation endproducts (RAGE) is a multiligand receptor and known to be implicated in various pathogenic conditions, such as diabetes, inflammatory disorder, Alzheimer disease, and cancer. In this study, the impact of RAGE gene polymorphisms on the susceptibility to hepatocarcinogenesis was explored. Four single-nucleotide polymorphisms (SNPs), rs184003 (1704G?>?T), rs1800624 (-374T?>?A), rs1800625 (-429T?>?C), and rs2070600 (Gly82Ser), as well as 1 gene polymorphism of RAGE gene, a 63?bp deletion allele (-407 to -345) were analyzed between 300 cancer-free subjects and 265 HCC cases. We detected a significant association of rs1800625 with the increased risk of HCC (odds ratio [OR], 2.565; 95% confidence interval [CI], 1.492-4.409 and adjusted odds ratio [AOR], 2.568; 95% CI, 1.418-4.653). However, patients who possess at least 1 polymorphic allele of rs1800625 are less prone to develop late-stage (stage III/IV, OR, 0.502; 95% CI, 0.243-1.037; P?=?0.059 and AOR, 0.461; 95% CI, 0.219-0.970; P?=?0.041) and large-size tumors (OR, 0.398; 95% CI, 0.183-0.864; P?=?0.017 and AOR, 0.351; 95% CI, 0.157-0.781; P?=?0.010). Furthermore, individuals bearing specific haplotypes of 4 RAGE SNPs tested are more inclined to have HCC. In conclusion, our data suggest a correlation of RAGE gene polymorphism rs1800625 with the early stage of liver tumorigenesis and implicate its protective role in the progression of HCC.

SUBMITTER: Su SC

PROVIDER: S-EPMC4602925 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Effects of RAGE Gene Polymorphisms on the Risk and Progression of Hepatocellular Carcinoma.

Su Shih-Chi SC Hsieh Ming-Ju MJ Chou Ying-Erh YE Fan Wen-Lang WL Yeh Chao-Bin CB Yang Shun-Fa SF

Medicine 20150801 34

Hepatocellular carcinoma (HCC) is a common malignancy of the liver, whose heterogeneous incidence reflects genetic variations among individuals in the main risk factors. The receptor for advanced glycosylation endproducts (RAGE) is a multiligand receptor and known to be implicated in various pathogenic conditions, such as diabetes, inflammatory disorder, Alzheimer disease, and cancer. In this study, the impact of RAGE gene polymorphisms on the susceptibility to hepatocarcinogenesis was explored. ...[more]

PMID: 26313784

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Project description:AimTo investigate the associiations between the polymorphisms of cell cycle pathway genes and the risk of hepatocellular carcinoma (HCC).MethodsWe enrolled 1127 cases newly diagnosed with HCC from the Tumor Hospital of Guangxi Medical University and 1200 non-tumor patients from the First Affiliated Hospital of Guangxi Medical University. General demographic characteristics, behavioral information, and hematological indices were collected by unified questionnaires. Genomic DNA was isolated from peripheral venous blood using Phenol-Chloroform. The genotyping was performed using the Sequenom MassARRAY iPLEX genotyping method. The association between genetic polymorphisms and risk of HCC was shown by P-value and the odd ratio (OR) with 95% confidence interval (CI) using the unconditional logistic regression after adjusting for age, sex, nationality, smoking, drinking, family history of HCC, and hepatitis B virus (HBV) infection. Moreover, stratified analysis was conducted on the basis of the status of HBV infection, smoking, and alcohol drinking.ResultsThe HCC risk was lower in patients with the MCM4 rs2305952 CC (OR = 0.22, 95%CI: 0.08-0.63, P = 0.01) and with the CHEK1 rs515255 TC, TT, TC/TT (OR = 0.73, 95%CI: 0.56-0.96, P = 0.02; OR = 0.67, 95%CI: 0.46-0.97, P = 0.04; OR = 0.72, 95%CI: 0.56-0.92, P = 0.01, respectively). Conversely, the HCC risk was higher in patients with the KAT2B rs17006625 GG (OR = 1.64, 95%CI: 1.01-2.64, P = 0.04). In addition, the risk was markedly lower for those who were carriers of MCM4 rs2305952 CC and were also HBsAg-positive and non-drinking and non-smoking (P < 0.05, respectively) and for those who were carriers of CHEK1 rs515255 TC, TT, TC/TT and were also HBsAg-negative and non-drinking (P < 0.05, respectively). Moreover, the risk was higher for those who were carriers of KAT2B rs17006625 GG and were also HBsAg-negative (P < 0.05).ConclusionOf 12 cell cycle pathway genes, MCM4, CHEK1 and KAT2B polymorphisms may be associated with the risk of HCC.

Project description:BackgroundThe association between TP53 R72P and/or MDM2 SNP309 polymorphisms and hepatocellular carcinoma (HCC) risk has been widely reported, but results were inconsistent. To clarify the effects of these polymorphisms on HCC risk, an updated meta-analysis of all available studies was conducted.MethodsEligible articles were identified by search of databases including PubMed, Cochrane Library, EMBASE and Chinese Biomedical Literature database (CBM) for the period up to July 2013. Data were extracted by two independent authors and pooled odds ratio (OR) with 95% confidence interval (CI) was calculated. Metaregression and subgroup analyses were performed to identify the source of heterogeneity.ResultsFinally, a total of 10 studies including 2,243 cases and 3,615 controls were available for MDM2 SNP309 polymorphism and 14 studies containing 4,855 cases and 6,630 controls were included for TP53 R72P polymorphism. With respect to MDM2 SNP309 polymorphism, significantly increased HCC risk was found in the overall population. In subgroup analysis by ethnicity and hepatitis virus infection status, significantly increased HCC risk was found in Asians, Caucasians, Africans, and HCV positive patients. With respect to TP53 R72P polymorphism, no significant association with HCC risk was observed in the overall and subgroup analyses. In the MDM2 SNP309-TP53 R72P interaction analysis, we found that subjects with MDM2 309TT and TP53 Pro/Pro genotype, MDM2 309 TG and TP53 Arg/Pro genotype, and MDM2 309 GG and TP53 Pro/Pro genotype were associated with significantly increased risk of developing HCC as compared with the reference MDM2 309TT and TP53 Arg/Arg genotype.ConclusionsWe concluded that MDM2 SNP309 polymorphism may play an important role in the carcinogenesis of HCC. In addition, our findings further suggest that the combination of MDM2 SNP 309 and TP53 Arg72Pro genotypes confers higher risk to develop HCC. Further large and well-designed studies are needed to confirm this association.

Dataset Information

Effects of RAGE Gene Polymorphisms on the Risk and Progression of Hepatocellular Carcinoma.

Publications

Effects of RAGE Gene Polymorphisms on the Risk and Progression of Hepatocellular Carcinoma.

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