New research published in the European Journal of Cancer found that people with metabolic syndrome (MetS) that persisted for more than 2 years were at an increased risk of developing cholangiocarcinoma (CCA).

Of the factors related to metabolic syndrome, persistently elevated waist circumference (hazard ratio (HR): 1.13; 95% CI, 1.05-1.22), fasting glucose levels (HR: 1.25; 95% CI, 1.18-1.32), and blood pressure (HR: 1.11; 95% CI, 1.04-1.18) were significantly associated with increased risk of CCA. In contrast, persistently elevated triglyceride levels were associated with a decreased risk of CCA (HR: 0.89; 95% CI, 0.85-0.94).

The authors noted, “Our finding suggests that MetS may be a potentially modifiable risk factor for CCA.”

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“Increased insulin, insulin-like growth factor-1 (IGF-1), and insulin-like growth factor-2 (IGF-2) levels may play a role in CCA growth by promoting cell proliferation and angiogenesis and inhibiting apoptosis,” the authors wrote. Increased levels of visceral adipose tissue may also release pro-inflammatory cytokines, leading to the formation of reactive oxygen species, faster cell cycle rates, and decreased tumor suppression.

The retrospective study included the medical records of 8,203,492 Korean individuals who underwent national health screenings between January 2009 and December 2010, and who were re-examined after 2 years and did not meet exclusion criteria. Study participants were then observed until death, loss to follow-up, or December 31st, 2017, whichever came first.

Individuals were then stratified into 4 categories based on their MetS status changes between the 2 health screenings. These categories were: patients who did not have MetS (MetS-free; 65.1% of individuals), those whose MetS resolved (MetS-improved; 10.3%), those who developed MetS (MetS-developed; 7.8%), and those who had MetS at both screenings (MetS-persistent; 16.8%). MetS was diagnosed in individuals who met at least 3 of the following 5 criteria: elevated waist circumference, elevated triglyceride levels, reduced HDL cholesterol levels, elevated blood pressure, or elevated fasting glucose levels.

A total of 7506 patients were identified as having CCA based on hospitalizations with both the International Classification of Diseases (ICD)-10-code (C code; C24, C221) and the special reimbursement code (V code; V193). The incidence rates per 1000 person-years were 0.13 for the MetS-free group compared to 0.36 for the MetS-persistent group. Log-rank testing of Kaplan-Meier curves showed that the incidence of CCA was consistently higher in the MetS-persistent group compared to the MetS-free group (P <.001).


Park J-H, Hong JY, Park YS, Kang G, Han K, Park JO. Persistent status of metabolic syndrome and risk of cholangiocarcinoma: a Korean nationwide population-based cohort study. Eur J Cancer. 2021;155:97-105. doi:10.1016/j.ejca.2021.06.052