Polymorphisms in MICA, but not in DEPDC5, HCP5 or PNPLA3, are associated with chronic hepatitis C-related hepatocellular carcinoma

Abstract

Recently, the MICA rs2596542 and DEPDC5 rs1012068 variants in Japanese individuals as well as the HCP5 rs2244546 and PNPLA3 rs738409 variants in European individuals have been found associated with hepatocellular carcinoma (HCC). The present study determined which single nucleotide polymorphism (SNP) is the most predictive for developing hepatitis C virus (HCV)-related HCC in a Japanese cohort. Of the 4 SNPs analysed, only the MICA genotypes were significantly associated with development of HCC (p = 0.0185). The major (MA), hetero (HE), and minor (MI) genotypes occurred in 40%, 41%, and 19% of HCC patients and in 43%, 47%, and 10% of non-HCC patients, respectively. Interestingly, the MICA genotype was significantly correlated with MICA mRNA and soluble protein levels. In patients older than 70 years, the MI genotype was significantly associated with HCC development. In addition, the MI genotype was related to HCC development when the platelet count range was 10–15 × 104/μL, corresponding with the fibrosis stage; but not when the range was less than 10, indicating advanced fibrosis; or greater than 15 × 104/μL, as mild fibrosis. Thus, polymorphisms in MICA, but not in DEPDC5, HCP5 or PNPLA3, are associated with HCC development in Japanese patients with chronic HCV infection.

PNPLA3 and TM6SF2 variants as risk factors of hepatocellular carcinoma across various etiologies and severity of underlying liver diseases

“…In this analysis, we did not perform correction for multiple testing because we considered this part of our study as a replication of previous findings. 9,10,[33][34][35][36][37] The different results between our study and GWAS studies could be explained by the difference in term of control group (chronic liver disease population vs. healthy population) and the lack of adjustment on fibrosis stage in GWAS. This discrepancy could also be explained by the difference in ethnicity with Asian population included in GWAS studies and European ancestries in our study.…”

“…In the literature, SNP identified in GWAS failed to be validated in other GWAS and in casecontrol studies available in the literature. 9,10,[33][34][35][36][37] Similarly, we failed to confirm an association between these SNP and HCC development except for rs7574865 STAT4 that were linked with HCC occurrence in HBV related HCC in our study, confirming the results of the original GWAS. In this analysis, we did not perform correction for multiple testing because we considered this part of our study as a replication of previous findings.…”

“…We also tested 7 SNP previously described as associated with HCC risk in GWAS. In the literature, SNP identified in GWAS failed to be validated in other GWAS and in case–control studies available in the literature . Similarly, we failed to confirm an association between these SNP and HCC development except for rs7574865 STAT4 that were linked with HCC occurrence in HBV related HCC in our study, confirming the results of the original GWAS.…”

“…Similarly, we failed to confirm an association between these SNP and HCC development except for rs7574865 STAT4 that were linked with HCC occurrence in HBV related HCC in our study, confirming the results of the original GWAS. In this analysis, we did not perform correction for multiple testing because we considered this part of our study as a replication of previous findings . The different results between our study and GWAS studies could be explained by the difference in term of control group (chronic liver disease population vs .…”

Interplay of PNPLA3 and HSD17B13 Variants in Modulating the Risk of Hepatocellular Carcinoma among Hepatitis C Patients

“…In fact, while the rs738409 mutation has been convincingly associated to liver carcinogenesis in alcoholic liver disease [28,29] and in nonalcoholic steatohepatitis [30,31], this association in viral hepatitis has been the subject of controversy [32,33]. While some authors reported an increased risk of HCC development in HCV patients carrying the G allele [34][35][36][37][38], others failed to confirm these findings [4,[39][40][41][42]. The reason for this discrepancy may belong to the different ethnicities of the study populations; in fact, the largest part of the studies failing to demonstrate the association of this SNP with HCC has been conducted on Asian populations.…”