Plasma miR-145-5p levels and risk of cancer-associated thrombosis-results from the HUNT study

The incidence of cancer-associated venous thromboembolism (CAT) has risen in recent decades, underscoring the need for novel risk biomarkers and mechanistic insights. MicroRNAs (miRNAs) have emerged as promising biomarkers for various diseases, with elevated miRNA-145-5p (miR-145-5p) levels linked to reduced venous thromboembolism (VTE) risk. We aimed to investigate the association between plasma miR-145-5p levels and risk of future VTE related to (CAT) and unrelated to cancer (non-CAT).

Plasma miR-145-5p levels were measured in a case cohort derived from the Trøndelag Health Study (HUNT3; N = 50 807). The study included 455 VTEs (95 CATs), occurring during 9 years of follow-up, and 1740 randomly sampled age-weighted subcohort participants. VTEs were classified as CAT if they occurred within 1 year before or 2 years after a cancer diagnosis. Multivariable adjusted hazard ratios (HRs) for CAT and non-CAT were estimated using weighted Cox regression, with cancer modeled as a time-varying covariate.

Increasing miR-145-5p levels were associated with lower risk of CAT (HR per 1 SD, 0.70; 95% CI, 0.52-0.96) and non-CAT (HR, 0.81; 95% CI, 0.72-0.91). Individuals in the highest miR-145-5p quartile had lower risk of both CAT (HR, 0.55; 95% CI, 0.25-1.20) and non-CAT (HR, 0.48; 95% CI, 0.33-0.69) than those in the lowest quartile.

High plasma miR-145-5p levels were associated with lower risk of CAT and non-CAT, suggesting that miR-145-5p has the potential to serve as a risk biomarker for CAT.