Risk Factors and Prevention of Viral Hepatitis-Related Hepatocellular Carcinoma

Zhang, Xinhe; Lin, Gen‐Min; Tian, Haoyu; Zeng, Zilu; Chen, Jiayu; Huang, Die; Sun, Ji; Guo, Jiaqi; Cui, Huipeng; Li, Yiling

doi:10.3389/fonc.2021.686962

Cited by 27 publications

(24 citation statements)

References 157 publications

(163 reference statements)

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“…HCC is caused by several genetic and environmental factors. Among these, large proportion of HCC cases occurred because of viral infection [ 11 ]. HCV-mediated HCC prevalence is increasing globally specifically in developing countries [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

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Analyzing PKC Gamma (+ 19,506 A/G) polymorphism as a promising genetic marker for HCV-induced hepatocellular carcinoma

et al. 2022

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Background HCC is a major health concern worldwide. PKC gamma, a member of the conventional PKC subclass, is involved in many cancer types, but the protein has received little attention in the context of single nucleotide polymorphisms and HCC. Therefore, the study aims to investigate the association of PKC gamma missense SNP with HCV-induced hepatocellular carcinoma. Methods The PKC gamma nsSNPs were retrieved from the ENSEMBL genome browser and the deleterious nsSNPs were filtered out through involvingPredictSNP2, CADD, DANN, FATHMM, FunSeq2 and GWAVA. Among the filtered nsSNPs, nsSNP rs1331262028 was identified to be the most pathogenic one. Through involving I-TASSER, ProjectHOPE, I-Mutant, MUpro, mCSM, SDM, DynaMut and MutPred, the influence of SNP rs1331262028 on protein structure, function and stability was estimated. A molecular Dynamic simulation was run to determine the conformational changes in mutant protein structure compared to wild. The blood samples were collected for genotyping analysis and for assessing ALT levels in the blood. Results The study identified for the first time an SNP (rs1331262028) of PRKCG to strongly decrease protein stability and induce HCC. The RMSD, RMSF, and Rg values of mutant and wild types found were significantly different. Based on OR and RR values of 5.194 and 2.287, respectively, genotype analysis revealed a higher correlation between the SNP homozygous wild Typeform, AA, and the disease while patients with genotype AG have higher viral load. Conclusion Outcomes of the current study delineated PKC gamma SNP rs1331262028 as a genetic marker for HCV-induced HCC that could facilitate disease management after further validation.

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Section: Discussionmentioning

confidence: 99%

“…Among these, large proportion of HCC cases occurred because of viral infection [ 11 ]. HCV-mediated HCC prevalence is increasing globally specifically in developing countries [ 11 ]. The major problem in most cancers is the early detection.…”

Section: Discussionmentioning

confidence: 99%

Analyzing PKC Gamma (+ 19,506 A/G) polymorphism as a promising genetic marker for HCV-induced hepatocellular carcinoma

et al. 2022

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“…This difference in gender distribution is thought to be closely related to hormone levels in men and their unhealthy lifestyles like overworking, staying up late and excessive drinking. Third, in terms of smoking status, studies have shown that smoking is a minor risk factor for HCC [ 30 , 31 ]. According to reports, smoking can increase the morbidity and mortality of HCC [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Contribution of PNPLA3 gene polymorphisms to hepatocellular carcinoma susceptibility in the Chinese Han population

Gong

et al. 2022

BMC Med Genomics

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Objectives The purpose of this study was to investigate the association of PNPLA3 single nucleotide polymorphisms (SNPs) (rs738409 C > G, rs3747207 G > A, rs4823173 G > A, and rs2896019 T > G) with hepatocellular carcinoma (HCC) susceptibility. Methods This case–control study included 484 HCC patients and 487 controls. Logistic regression analysis was performed to study the associations of PNPLA3 gene polymorphisms with HCC susceptibility, and odds ratios with their corresponding 95% confidence intervals were calculated to evaluate these correlations. Results In the overall analysis, we found that the G allele (OR = 1.25, 95% CI = 1.04–1.50, p = 0.018, false discovery rate (FDR)-p = 0.035) and GG genotype (OR = 1.59, 95% CI = 1.06–2.39, p = 0.024, FDR-p = 0.048) of rs2896019 were significantly associated with increased HCC susceptibility. In stratified analysis, we found that all four SNPs were related to increased HCC susceptibility in subjects aged > 55 years. In haplotype analysis, the GAAG haplotype was significantly associated with increased HCC susceptibility (OR = 1.25, 95% CI = 1.03–1.53, p = 0.023, FDR-p = 0.046). Besides, we noticed that rs738409 was significantly correlated with alpha-fetoprotein (AFP) (p = 0.007), and HCC patients with the GG genotype had a higher level of AFP. Conclusions Our study suggested that PNPLA3-rs2896019 was significantly associated with an increased susceptibility to HCC.

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“…The onset of HCC is frequently observed in patients with high alcohol intake and chronic viral hepatitis B or C infection, accounting for greater than 50% of cases [ 4 ]. Prevention of hepatitis-induced HCC occurs through prevention of exposure, inoculation with the hepatitis B vaccine (currently there is no hepatitis C vaccine), and/or treatment with targeted antiviral medications [ 5 ]. The expansion of vaccine inoculation in the United States, which was incorporated into the infant inoculation schedule in 1991, has greatly reduced the risk of hepatitis and cancer related mortality [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Obesity Management in the Primary Prevention of Hepatocellular Carcinoma

Zunica

Heintz

Axelrod

et al. 2022

Cancers

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Hepatocellular carcinoma (HCC) is the most frequent primary hepatic malignancy and a leading cause of cancer-related death globally. HCC is associated with an indolent clinical presentation, resulting in frequent advanced stage diagnoses where surgical resection or transplant therapies are not an option and medical therapies are largely ineffective at improving survival. As such, there is a critical need to identify and enhance primary prevention strategies to mitigate HCC-related morbidity and mortality. Obesity is an independent risk factor for the onset and progression of HCC. Furthermore, obesity is a leading cause of nonalcoholic steatohepatitis (NASH), the fasting growing etiological factor of HCC. Herein, we review evolving clinical and mechanistic associations between obesity and hepatocarcinogenesis with an emphasis on the therapeutic efficacy of prevailing lifestyle/behavioral, medical, and surgical treatment strategies for weight reduction and NASH reversal.

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Risk Factors and Prevention of Viral Hepatitis-Related Hepatocellular Carcinoma

Cited by 27 publications

References 157 publications

Analyzing PKC Gamma (+ 19,506 A/G) polymorphism as a promising genetic marker for HCV-induced hepatocellular carcinoma

Analyzing PKC Gamma (+ 19,506 A/G) polymorphism as a promising genetic marker for HCV-induced hepatocellular carcinoma

Contribution of PNPLA3 gene polymorphisms to hepatocellular carcinoma susceptibility in the Chinese Han population

Obesity Management in the Primary Prevention of Hepatocellular Carcinoma

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