Identification of novel genetic factors and genetic risk assessment models for non-viral HCC

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09446
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Hiroshima University (2018-2019); Institute of Physical and Chemical Research (2017)
• Principal Investigator: Daiki Miki 広島大学, 医系科学研究科(医), 講師 (10584592)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: SNP / 肝癌 / NASH / NAFLD / SVR / HCV

Outline of Final Research Achievements

Recently, it was reported that a single nucleotide polymorphism (SNP) rs17047200 located within the intron of TLL1 gene was associated with development of hepatocellular carcinoma (HCC) after eradication of hepatitis C virus (HCV). As a result of our study, we observed protective tendencies of rs17047200 T allele for the risk of HCC development in SVR patients as well as chronic HCV patients and chronic HBV patients. We also observed a similar tendency for the risk of fibrosis severity in SVR patients.
The SNP in PLPNA3 is the most famous genetic factor which confers susceptibility to nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Our findings revealed that SNPs of PNPLA3 and neighbor genes were associated not only to NAFLD/NASH susceptibility, but also to HCC development with stronger effects than those for NAFLD/NASH susceptibility. In addition, a novel candidate SNP which causes T94A substitution in FABP1 might affect NASH/NAFLD-related HCC.

Free Research Field

肝臓学、ゲノム医科学

Academic Significance and Societal Importance of the Research Achievements

現在、肝炎ウイルス非存在下における肝癌が増加傾向であるが、そのリスク因子は十分に解明されていない。より効率的なスクリーニングを行うためにも、リスク因子のさらなる解明が急務である。遺伝的要因について解析を行った本研究の結果、これまでの報告とは異なる結果や、これまでに報告の無かった結果が得られた。これらの結果については、さらなる検証が必要ではあるものの、今後、肝発癌リスクの予測に役立つことが期待できる。