Serum homocysteine-based traffic light triage colonoscopy screening in colorectal cancer at-risk patients: A prospective cohort study.

Background: Elevated plasma homocysteine (Hcy) levels are associated with increased risk of colorectal cancer (CRC), particularly in patients with systemic inflammation or chronic conditions.

Aim: To evaluate serum Hcy levels as a predictive marker of lesion risk and CRC to prioritize patients undergoing diagnostic colonoscopy.

Methods: We conducted a prospective cohort study of 301 fecal occult blood test-positive patients at San Agustín University Hospital in Asturias, Spain. Plasma Hcy levels were measured prior to the colonoscopy and classified into three thresholds: ≤ 12, 12-15, and > 15 μmol/L. Colonoscopy and histopathology determined the presence of low-risk, high-risk polyps or adenocarcinoma. Predictive performance of serum Hcy to detect lesions was assessed using logistic regression and diagnostic accuracy measures, including models adjusted for age and sex.

Results: Median Hcy levels rose progressively with lesion severity, reaching 15.3 μmol/L in adenocarcinoma (P < 0.001). Higher levels were also observed in men and individuals aged 65 or older. A threshold above 15 μmol/L showed good sensitivity (76.6%) and positive predictive value (87.2%) for detecting adenocarcinoma. When combined with age and sex, predictive accuracy improved (area under the receiver operating characteristic curve = 0.706). Based on these findings, we propose a three-tier triage system: Green (≤ 12 μmol/L in both sexes, colonoscopy within three months), Yellow (> 12-15 μmol/L in men, intervention within one month and red (≥ 15 in either sex or > 12 μmol/L in women, immediate colonoscopy).

Conclusion: Serum Hcy is a clinically useful biomarker for identifying high-risk colorectal lesions and cancer, particularly when interpreted in combination with age and sex. This composite model improves predictive accuracy and enables a structured three-tiered triage system that supports faster colonoscopy scheduling for at-risk groups. The traffic light approach offers a low cost, scalable strategy to reduce delays and optimize resource use in CRC screening, especially in public health systems with limited endoscopic capacity.