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Increased serological cancer-associated biomarkers and risk of development of primary malignancy after large bowel endoscopy

The results of the study by Hvolris et al [1] concerning a possible association between serological biomarker levels at large bowel endoscopy due to symptoms attributable to bowel neoplasia and the risk of developing a subsequent malignant disease have led to an editorial.[2] The original study (2004–2005) included pre-endoscopy blood collections and preand post-endoscopy data from 4,509 subjects.[3] The post-endoscopy diagnoses included in rank order: colorectal cancer, extra-colonic malignancies, adenomas, other non-neoplastic bowel findings and clean colorectum. Retrospectively, the serological protein biomarkers CA19-9, CEA, TIMP-1 and YKL-40 were determined in all available blood samples.[3,4] Subsequently, the value of the biomarkers for early detection of large bowel neoplasia was calculated.[3,4] Briefly, it was shown that the biomarker levels were increased among some subjects diagnosed with bowel neoplasia, but the levels were also increased among some subjects diagnosed with diverticula and infrequently among subjects with clean colorectum. Due to the unique 10-digit computerized, central personal registration (cpr) number given to all Danish Citizens the included subjects could be observed in the subsequent years. The well-established relation of the four biomarkers to neoplastic diseases directed an observational study of the entire study population with the aim of evaluating the biomarker levels and risk of developing subsequent malignant diseases. Indeed, results from subjects diagnosed with clean colorectum indicated an association between increased biomarker levels and increased risk of developing subsequent malignant diseases.[5] Subjects diagnosed with diverticula were evaluated in a subsequent study. Of the 1,021 patients, 148 were diagnosed with a subsequent primary malignancy, mostly extra-colonic diseases. The patients were separated into three groups: 0: none of four biomarkers were increased; 1: one of four biomarkers was increased; 2: two or more biomarkers were increased. As shown in the publication patients with diverticula and none of four biomarkers increased had a risk of subsequent malignancy similar to the back-ground population, while both groups 1 and 2 with increased biomarker levels had significantly increased risk of developing a subsequent primary malignant disease. It is needed to be stressed that the study did not focus on the diagnosis of diverticula and risk of subsequent development of a primary malignant disease. Due to group 0, an additional control group was not needed. Future study results will include subjects diagnosed with adenoma at the primary large bowel endoscopy, increased biomarker levels and risk of developing subsequent primary malignancy including intraand extra-colonic diseases. Finally, the achieved results will be validated in large cohorts of subjects, who have been offered colonoscopy due to a positive screen FIT test, and from whom blood samples have been collected.