Increased serological, cancer-associated protein biomarker levels at diagnosis of large bowel adenoma: Risk of subsequent primary malignancy?

Abstract

Background: Blood-based, cancer-associated biomarkers may detect subjects at risk of having neoplastic diseases. The aim of the present study was to evaluate whether elevated serological protein biomarker levels may identify adenoma patients, who are at increased risk of being diagnosed with subsequent primary malignancy.

Methods: Levels of CEA, CA19-9, TIMP-1 and YKL-40 were determined in blood samples collected prior to diagnostic bowel endoscopy due to symptoms of colorectal neoplasia. Follow-up time was ten years, and identified adenoma patients, who were diagnosed with subsequent primary intra- or extra-colonic malignant diseases. The biomarker levels were also determined in 400 subjects, who underwent diagnostic colonoscopy, had clean colorectum and were without apparent co-morbidity; these levels were used as reference levels. In the present study, biomarkers were interpreted as elevated when levels were above the reference intervals adjusting for age and gender. The 1-year and 5-years cumulative incidences were calculated.

Results: Primary malignancies were identified in 175 (19%) of the 923 subjects diagnosed with adenomas at the primary bowel endoscopy. In detail, 20 of the 175 subjects were diagnosed with colorectal cancer (CRC) and 155 subjects with extra-colonic cancers. Thirty patients were diagnosed with malignancy within the first year. Three groups were established: 0: no elevated biomarkers; 1: 1 of the 4 biomarkers elevated; and 2: ≥2 biomarkers elevated. The cumulative 5-years incidence of malignancy was: 0: 6.9%; 1: 11.8%; and 2: 17.5% (p = .0009).

Conclusion: Elevated blood-based, cancer-associated protein biomarker levels in subjects diagnosed with adenomas at large bowel endoscopy identifies subjects at increased risk of being diagnosed with subsequent primary malignancy.

Disclosure statement

Determinations of CEA, CA19-9 and TIMP-1 in plasma samples were performed at Abbott Centre’s of Excellence in Munich, Germany and Amsterdam the Netherlands free of charge. Gerard Davis is an employee of Abbott Laboratories Inc., Abbott Park, IL, USA.

Acknowledgments

The research nurses, secretaries and technicians at the participating hospital departments and laboratories are thanked for their skillful work.

Additional information

Funding

The study received financial support from The Danish Cancer Society, The Kornerup Fund, The Aage and Johanne Louis-Hansen Fund, The Aase and Ejnar Danielsen Fund, The Walter and O. Kristiane Christensen Fund, The Kathrine and Vigo Skovgaard Fund, Den Midtjyske Bladfond, The Agnes and Poul Friis Fund, The Glunz and Jensen Fund, The Sophus and Astrid Jacobsen Fund, The Arvid Nilsson Fund, The Danish Bank Fund, The Johannes Fog Fund, The Eva and Henry Fraenkel Fund, The Hartmann Bros. Fund, The KID Fund, The Henrik Henriksen Fund, The King Christian X’s Fund, The Oda and Hans Svenningsen Fund, The Else and Mogens Wedell-Wedellsborg Fund, The Einar Willumsen Fund, The Willy and Ingeborg Reinhard Fund, The Friedrich and Else Boehm Fund, The Toyota Fund, The IMK Fund, The Danish Medical Research Fund, The Beckett Fund and Hvidovre University Hospital.