Chemoprevention of Colorectal Cancer-With Emphasis on Low-Dose Aspirin and Anticoagulants.

Background and Aims: Colorectal cancer (CRC) remains the third most common cancer worldwide and a leading cause of cancer-related death. Chemoprevention through widely used pharmaceutical agents has garnered increasing interest due to its potential cost-effectiveness and accessibility. This review summarizes current evidence from observational studies, randomized controlled trials, and meta-analyses on the association between commonly prescribed medications and CRC incidence and survival, with particular emphasis on low-dose aspirin and oral anticoagulants (OACs). Scope: Aspirin is the most extensively studied agent, with substantial evidence supporting its protective effect on CRC-specific survival, particularly in long-term users, those with COX-2 overexpression, or PIK3CA mutations. OACs have recently gained attention due to their association with increased gastrointestinal bleeding, which may facilitate earlier CRC detection. While emerging evidence suggests a possible survival benefit through this mechanism, data remain heterogeneous and affected by methodological challenges such as lead-time bias. Metformin is associated with improved CRC outcomes, primarily in patients with type 2 diabetes, though its direct anti-tumor potential remains under investigation. Corticosteroids, statins, and beta-blockers have both limited and inconclusive evidence. Finally, recent studies on vitamin D, calcium, and folic acid suggest inconsistent associations, often confounded by lifestyle factors or underlying comorbidities.

Conclusions

While promising, chemoprevention strategies require further validation in well-designed, mechanistically informed studies that account for confounding variables, treatment duration, and tumor biology. Personalized prevention-guided by genetic, molecular, and clinical risk factors-represents a promising path forward.