Risk of Colorectal Neoplasia in First-Degree Relatives of Colorectal Advanced Adenoma Patients: A Systematic Review
Chuong Dinh Nguyen, Luan Minh Dang, Nhan Quang Le, Thong Duy Vo, Duc Trong Quach, Siew C. NgBackground:
Colorectal advanced adenomas (CAAs) are key colorectal cancer (CRC) precursors. While familial CRC risk is well-established, the neoplastic risk (adenoma, CAA, CRC) in first-degree relatives (FDRs) of CAA patients is unclear.
Aims:
This systematic review aimed to quantify this risk and identify risk-modifying factors.
Methods:
Per PRISMA guidelines, we systematically searched MEDLINE, EMBASE, and CENTRAL through May 2025 for observational studies comparing neoplasm risk in FDRs of CAA probands versus controls. Two reviewers independently extracted data and assessed bias (Newcastle-Ottawa Scale). A qualitative synthesis was performed due to heterogeneity.
Results:
Of 421 records identified, four studies from diverse populations were included. FDRs of CAA patients had a significantly increased risk for any adenoma (OR/RR 1.33-3.29, with 95% CIs ranging from 0.96 to 5.03) and advanced neoplasia (CAA/CRC) (OR/RR 1.65-6.33, 95% CIs 1.01-43.8). CRC risk findings were inconsistent; two larger studies showed a modest risk increase (RR/OR 1.7-2.3, 95% CIs 1.01-5.09), while two smaller studies reported non-significant results. Proband age <60 years, adenoma multiplicity, and male sex of the FDR emerged as potential risk modifiers in individual studies, though evidence is limited. Regarding proband adenoma location, a distal lesion was more consistently associated with increased familial risk, although an association with proximal lesions was also reported.
Conclusion:
FDRs of CAA patients appear to have an elevated risk for colorectal adenomas, particularly CAAs, although evidence certainty is limited. Documented family history of CAA may warrant consideration as one of several factors in future risk-stratified screening approaches; however, the current evidence is insufficient to define CAA-specific screening intervals beyond existing guideline frameworks. Further research is needed to validate risk estimates and optimize screening strategies.