Telomere length and risk of cirrhosis, hepatocellular carcinoma, and cholangiocarcinoma in 63,272 individuals from the general population

Hepatology. 2024 Apr 1;79(4):857-868. doi: 10.1097/HEP.0000000000000608. Epub 2023 Sep 19.

Abstract

Background and aims: Inherited short telomeres are associated with a risk of liver disease, whereas longer telomeres predispose to cancer. The association between telomere length and risk of HCC and cholangiocarcinoma remains unknown.

Approach and results: We measured leukocyte telomere length using multiplex PCR in 63,272 individuals from the Danish general population. Telomere length and plasma ALT concentration were not associated (β = 4 ×10 -6 , p -value = 0.06) in a linear regression model, without any signs of a nonlinear relationship. We tested the association between telomere length and risk of cirrhosis, HCC, and cholangiocarcinoma using Cox regression. During a median follow-up of 11 years, 241, 76, and 112 individuals developed cirrhosis, HCC, and cholangiocarcinoma, respectively. Telomere length and risk of cirrhosis were inversely and linearly associated ( p -value = 0.004, p for nonlinearity = 0.27). Individuals with telomeres in the shortest vs. longest quartile had a 2.25-fold higher risk of cirrhosis. Telomere length and risk of HCC were nonlinearly associated ( p -value = 0.009, p -value for nonlinearity = 0.01). This relationship resembled an inverted J-shape, with the highest risk observed in individuals with short telomeres. Individuals with telomeres in the shortest versus longest quartile had a 2.29-fold higher risk of HCC. Telomere length was inversely and linearly associated with the risk of cholangiocarcinoma. Individuals with telomeres in the shortest versus longest quartile had a 1.86-fold higher risk of cholangiocarcinoma.

Conclusions: Shorter telomere length is associated with a higher risk of cirrhosis, HCC, and cholangiocarcinoma.

MeSH terms

  • Bile Duct Neoplasms* / epidemiology
  • Bile Duct Neoplasms* / genetics
  • Bile Duct Neoplasms* / pathology
  • Bile Ducts, Intrahepatic / pathology
  • Carcinoma, Hepatocellular* / epidemiology
  • Carcinoma, Hepatocellular* / genetics
  • Carcinoma, Hepatocellular* / pathology
  • Cholangiocarcinoma* / epidemiology
  • Cholangiocarcinoma* / genetics
  • Cholangiocarcinoma* / pathology
  • Humans
  • Leukocytes
  • Liver Cirrhosis / genetics
  • Liver Cirrhosis / pathology
  • Liver Neoplasms* / epidemiology
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / pathology
  • Risk Factors
  • Telomere / genetics