Association between host factor and hepatocellular carcinoma in non-viral patients with type 2 diabetes

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09388
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: National Center for Global Health and Medicine
• Principal Investigator: MASAAKI KORENAGA 国立研究開発法人国立国際医療研究センター, その他部局等, その他 (70420536)
• Co-Investigator(Kenkyū-buntansha): 西田 奈央 国立研究開発法人国立国際医療研究センター, その他部局等, 上級研究員 (50456109)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 2型糖尿病 / 肝細胞癌 / PNPLA3 / JAZF1

Outline of Final Research Achievements

Type 2 diabetes mellitus (T2DM) is an established independent risk factor for hepatocellular carcinoma (HCC). We recruited 389 patients with These patients were divided into two groups, T2DM patients with HCC (DM-HCC, n = 59) or those without HCC (DM-non-HCC, n = 330). The SNP rs738409 located in PNPLA3 was the greatest risk factor associated with HCC in non-viral hepatitis patients with T2DM. The frequency of the PNPLA3 G allele was significantly higher among DM-HCC individuals than DM-non-HCC individuals. Among individuals homozygous for the PNPLA3 G allele , the frequency of the JAZF1 rs864745 G allele was significantly higher among DM-HCC individuals than DM-non-HCC individuals. The influence of PNPLA3 and JAZF1 was independent of age, sex, and body mass index after multivariable logistic regression analysis. There were no HCC patients who had risk SNPs after 5 years observation.　To explorer HCC patients with DM、we used other markers such as M2BPGi, IL-34,Fibroscan, and MRI.

Free Research Field

消化器・肝臓病学

Academic Significance and Societal Importance of the Research Achievements

本研究により、2型糖尿病合併症例から肝発癌・予後の実態が明らかとなった。また十分とは言えなものの、わが国でも増加中の2型糖尿病患者さんに対してPNPLA3, JAZF1という遺伝子を用いることで肝発癌危険群が抽出可能となることで、我が国の肝炎治療後・脂肪肝・2型闘病尿医療の均てん化に貢献でき、更なる遺伝子検索と礎となった。更に今後欧米化が顕著となり、糖代謝異常が増加すると予測される東アジア地域医療にも利用可能であると考えられ、多くの地域に貢献できると推測する