• Summarizes current screening guidance for familial colorectal cancer. • Highlights advances in genetic risk models and personalized surveillance. • Reviews emerging non-invasive molecular tests improving early CRC detection. • Examines lifestyle–genetic interactions shaping hereditary CRC risk. • Discusses AI-enhanced colonoscopy and precision tools for risk-based screening. Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, with approximately 25–30% of cases exhibiting a familial component driven by germline mutations in DNA mismatch repair genes (Lynch syndrome) or the APC gene (familial adenomatous polyposis). Despite advances in screening and early detection, significant challenges persist in identifying at-risk individuals, optimizing surveillance strategies and addressing disparities in access to genetic testing and preventive care. This narrative review synthesizes current evidence on the genetic underpinnings, modifiable risk factors and personalized screening approaches for familial CRC. We highlight the critical interplay between hereditary predisposition and environmental exposures including diet, obesity, smoking and gut microbiome alterations, which cumulatively influence disease penetrance and clinical outcomes. Emerging predictive models integrating family history, polygenic risk scores and proteomic biomarkers offer unprecedented opportunities for risk stratification, enabling tailored screening initiation and intervals that balance clinical efficacy with cost-effectiveness. Novel non-invasive biomarkers, such as circulating tumor DNA and stool RNA tests, demonstrate promising sensitivity and specificity, potentially enhancing patient adherence while complementing gold-standard colonoscopy. Furthermore, artificial intelligence-assisted endoscopy and comprehensive genetic panels are reshaping precision oncology by improving adenoma detection rates and guiding targeted therapies. Addressing social determinants of health and implementing structured genetic counseling remain essential to achieving equitable CRC prevention. By transitioning from age-based to individualized, risk-adapted screening paradigms, healthcare systems can significantly reduce CRC incidence and mortality, particularly among genetically predisposed populations.
Maria-Alexia et al. (Sun,) studied this question.