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 extracolonic 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 ¼ .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.

Serological cancer-associated protein biomarker levels at bowel endoscopy: Increased risk of subsequent primary malignancy

“…In detail, 33 subjects were subsequently diagnosed with CRC and 482 subjects with various extra-colonic cancers. In total, 455 subjects had high risk adenomas and 384 subjects had low risk adenomas -defined in a previous study [10].…”

“…The frozen samples were under 24/7 electronic surveillance. Plasma levels of the prespecified protein biomarkers CEA, CA19-9, TIMP-1 and serum levels of YKL-40 were determined as shown previously to identify a potential relation to endoscopy findings [8][9][10].…”

“…Events registered within 6 months from the initial bowel endoscopy were not included for further analysis (N = 127). Subjects with HNPCC or FAP were excluded, as described previously [10].…”

“…Previously our research group has analyzed three different subgroups from a population recruited in 2004-05 including 4,990 subjects with symptoms attributable to CRC in prospective studies. The three studies included subjects without findings at colorectal endoscopy, subjects with non-neoplastic lesions at colorectal endoscopy and subjects with colorectal adenomas [8][9][10]. Results from these three studies demonstrated an association between elevated cancer-associated biomarker levels and development of subsequent malignant diseases including CRC [8][9][10].…”

“…The three studies included subjects without findings at colorectal endoscopy, subjects with non-neoplastic lesions at colorectal endoscopy and subjects with colorectal adenomas [8][9][10]. Results from these three studies demonstrated an association between elevated cancer-associated biomarker levels and development of subsequent malignant diseases including CRC [8][9][10].…”