Novel findings on risk factors for cholangiocarcinoma (CCA) may suggest how to prevent this disease, according to a recent study.

Nonalcoholic fatty liver disease (NAFLD), cholelithiasis, and liver fat content (LFC) are among the putative risk factors that can causally increase the risk of CCA following false discovery rate correction, reported Guoyue Lv, of the First Hospital of Jilin University in Changchun, China, and colleagues.

“The results suggested that the genetic predispositions to higher LFC, NAFLD, and cholelithiasis were causal risk factors of CCA, and LFC and cholelithiasis were two independent ones,” the authors wrote.

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These data were published online in the journal Frontiers in Pharmacology.

Read more about CCA epidemiology

This Mendelian randomization (MR) study included 26 potential risk factors associated with CCA. The researchers used the Genome-Wide Association Study to determine each risk factor’s corresponding genetic variant. Inverse-variance weighted, multivariable, mediation Mendelian randomization, and false discovery rate analysis aided in identifying casualty and independent factors.

Moreover, an inherited increase in LFC independently increased the risk of CCA from cholelithiasis with an odds ratio of 1.88 (95% CI, 1.39 to 2.55). Notably, both entities can be prevented, hence lowering the risk of CCA.

Other results showed that the odds of CCA went up with a rise in the LFC as indicated by an odds ratio of 2.12 (95% CI, 1.66 to 2.71). The risk of developing CCA also rose, given a hereditary predisposition to cholelithiasis, as demonstrated by an odds ratio of 2.17 (95% CI, 1.47 to 3.20).

When managing the mediator cholelithiasis, the indirect effect was not statistically significant, with an indirect odds ratio of 0.95 (95% CI, 0.85 to 1.07) in the mediation MR analysis.

“This MR study fills the gap of the empirical risk factors of CCA between basic research and clinical observation to some extent,” the study concluded.


Chen L, Fan Z, Sun X et al. Examination on the risk factors of cholangiocarcinoma: a Mendelian randomization study. Front Pharmacol. Published online August 26, 2022. doi:10.3389/fphar.2022.900424