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

doi:10.3748/wjg.v31.i34.109718

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Prospective Study

World J Gastroenterol. Sep 14, 2025; 31(34): 109718
Published online Sep 14, 2025. doi: 10.3748/wjg.v31.i34.109718

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

Francisco Xavier Cano, José María Duque, Lucia Seoane, Miguel Puga-Tejada, Alejandra Espinoza de los Monteros, Pablo Bermeo, Eduardo Junquera, Daniel Pérez, Jimmy Martin-Delgado, Monica Santelli, Carla Pérez, Francisco Javier Pérez Rivera

Francisco Xavier Cano, Alejandra Espinoza de los Monteros, Pablo Bermeo, Jimmy Martin-Delgado, Monica Santelli, Instituto de Investigación e Innovación en Salud Integral, Universidad Católica de Santiago de Guayaquil, Guayaquil 090615, Guayas, Ecuador

Francisco Xavier Cano, Department of Gastroenterology, Hospital de Especialidades Alfredo G. Paulson, Guayaquil 090514, Guayas, Ecuador

José María Duque, Eduardo Junquera, Daniel Pérez, Department of Digestive Service, Hospital Universitario San Agustín de Aviles, Aviles 33401, Asturias, Spain

Lucia Seoane, Department of Digestive Service, Hospital Universitario Lucus Augusti, Lugo 27003, Galicia, Spain

Miguel Puga-Tejada, Department of Clinical Research & Biostatistics, Instituto Ecuatoriano de Enfermedades Digestivas, Guayaquil 090505, Guayas, Ecuador

Alejandra Espinoza de los Monteros, Jimmy Martin-Delgado, Department of Clinical Research, Hospital de Especialidades Alfredo G. Paulson, Guayaquil 090514, Guayas, Ecuador

Carla Pérez, Department of Biochemistry Service, Hospital Público de Verín, Ourense 32600, Galicia, Spain

Francisco Javier Pérez Rivera, Doctoral Department, Universidad de Leon, Leon 24004, Castille-Leon, Spain

Author contributions: Cano FX designed and conducted the study; Seoane L, Junquera E, Pérez D, Santelli M, and Pérez D conducted the data collection and preliminary data review; Martin-Delgado J and Puga-Tejada M contributed to the statistical analysis; Pérez Rivera FJ and Duque JM supervised the study; Espinoza de los Monteros A and Bermeo P wrote and edited the manuscript.

Institutional review board statement: This study was approved by the Hospital Ethics Committee of Asturias (official letter No. 244-18) in addition to the Heads of the Digestive and Clinical Biochemistry Service of the San Agustín University Hospital.

Clinical trial registration statement: This study is a prospective observational cohort and was not registered as a clinical trial, as it did not involve assignment of interventions to human participants.

Informed consent statement: Patients were required to sign their informed consent prior to the endoscopic procedure according to the Organic Law on the Protection of Personal Data art. 15, 1999.

Conflict-of-interest statement: The authors report no relevant conflicts of interest.

CONSORT 2010 statement: The authors have read the CONSORT 2010 Statement, and the manuscript was prepared and revised accordingly.

Data sharing statement: sharing statement: The technical appendix, statistical code, and dataset are available from the corresponding author at francisco.cano@cu.ucsg.edu.ec.

Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

Corresponding author: Francisco Xavier Cano, MD, PhD, Professor, Researcher, Instituto de Investigación e Innovación en Salud Integral, Universidad Católica de Santiago de Guayaquil, Av. Pdte. Carlos Julio Arosemena Tola, Guayaquil 090615, Guayas, Ecuador. francisco.cano@cu.ucsg.edu.ec

Received: May 20, 2025
Revised: July 5, 2025
Accepted: August 13, 2025
Published online: September 14, 2025
Processing time: 109 Days and 4.2 Hours

Abstract

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.

Keywords: Homocysteine; Predictive value of a test; Colonoscopy; Colorectal cancer; Cancer screening

Core Tip: In this study, we propose a traffic-light triage model based on serum homocysteine levels, sex, and age to prioritize colonoscopy after a positive fecal occult blood test. A green light (≤ 12 micromoles per liter in both sexes) indicates low risk and allows colonoscopy within three months. A yellow light (12-15 micromoles) in men suggests high-risk polyps and requires colonoscopy within one month. In women, the same range is already associated with adenocarcinoma and warrants immediate intervention. A red light (> 15 micromoles) in either sex is strongly associated with cancer and indicates the need for urgent colonoscopy.