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

Abstract

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