The role of PCSK9 in cancer risk: Population-level evidence and mechanistic insights

Proprotein convertase subtilisin/kexin type 9 (PCSK9), which promotes the degradation of low-density lipoprotein receptors, has become a major therapeutic target for hyperlipidemia and cardiovascular disease. Beyond lipid regulation, emerging evidence has identified potential roles for PCSK9 in cancer. Experimental studies support the multifaceted involvement of PCSK9 in malignancies, including immune regulation, apoptosis, metastasis, invasion, and lipid reprogramming. In recent years, a growing body of population-based evidence has drawn increasing epidemiological attention to the association between PCSK9 and cancer incidence and prognosis; however, the available evidence remains insufficient to support definitive conclusions. To date, a comprehensive synthesis of population-level evidence remains lacking. Thus, this review summarizes existing epidemiological findings and potential biological mechanisms underlying the role of PCSK9 in cancer and outlines perspectives for future research to bridge current knowledge gaps and provide evidence supporting interventions for populations at an elevated risk of both cardiovascular disease and cancer.