870 Increased Soluble Cancer-Associated Biomarker Levels at Colonoscopy and Subsequent Long-Term Risk of Primary Cancer

Background: The majority of patients with colorectal cancer (CRC) have increased levels of soluble cancer-associated biomarkers at diagnosis of primary disease. Subjects with clean colorectum at colonoscopy may however, also have increased levels of such biomarkers. The aim of the present study was to evaluate a possible association between increased levels of soluble TIMP-1, CEA, CA19-9 and YKL-40 in subjects offered colorectal endoscopy without findings of neoplastic bowel lesions and subsequent long-term risk of developing a primary malignant disease. Methods: During 2004/05 4,509 subjects were included in a multicenter study with collection of blood samples before sigmoidoand/or colonoscopy due to symptoms of CRC. The aim was to evaluate a possible relation between certain biomarkers and subsequent findings at endoscopy. A subgroup of 1,025 subjects had findings of diverticula and was chosen as research group, because the median age was similar to the subjects diagnosed with colorectal neoplasia. The levels of TIMP-1, CEA and CA19-9 were determined in EDTA plasma at an automatic analysis platform Architect® at Abbotts Center of Excellence, Amsterdam and YKL-40 was determined on a validated commercially available ELISA platform (Quidell, USA) at Herlev Hospital. With cut-point 12.31.2012 the subjects, who have developed a primarymalignant disease, except skin cancer, were identified and a relation between the biomarker levels at endoscopy and long-term risk of developing malignancy was calculated. On the basis of calculated normal levels, the relation with the biomarkers was separated into three groups: 0 = none of the four increased; 1 = one of the four increased; 2 = two or more of the four increased. In addition, the time from endoscopy to development of malignancy within the first five years was included; the model also includes an analysis of competing risk of dead before development of malignancy. Results: In total, 152 of the 1,025 subjects with diverticula developed a primary malignant disease within the observation period. Univariate analyses of the biomarker levels in the three predefined groups showed that TIMP-1 (p=0.0004), CEA (p=0.009) and CA19-9 (p=0.028) were significantly associated with development of malignancy. In a subsequent multivariate analysis including the three biomarkers showed that increased levels were associated with development of subsequent malignancy (p=0.0014). The cumulated risk of developing a primary malignant disease within the first five years was: group 0: 0.075 (0.055-0.099); group 1: 0.088 (0.059-0.126); group 2: 0.167 (0.120-0.221). Conclusion: Increased levels of the soluble biomarkers plasma TIMP-1, CEA and CA19-9 at endoscopy with findings of diverticula are associated with subsequent risk of developing a primary malignant disease.