| dc.description.abstract | Objective: Obesity is associated with increased risk of colorectal cancer (CRC), but the mechanisms linking the two conditions are not completely understood. The primary objective of this thesis was to investigate weight status in relation to comorbidities and biomarkers of obesity and inflammation in a subgroup of CRC patients from a multicenter randomized controlled intervention trial. In this trial, dried blood spot (DBS) will be used as the main blood collection method for measuring long-term effects of intervention, thus demanding the validation of new and relevant biomarkers. Therefore, we aimed at developing and validating a method to measure suPAR, a novel diagnostic biomarker, in DBS samples.
Subjects and methods: By May 2013, 41 newly diagnosed CRC patients aged 50-78 years were included in this study. Anthropometric measures and measures of physical function were recorded pre- and two months post-surgery. Pre-surgery, plasma adipokines and cytokines were analyzed by multiplex technology. suPAR was measured pre-surgery in DBS samples using a modified commercially available ELISA assay, and validated against plasma levels.
Results: We found that it was possible to measure suPAR in DBS and that DBS levels correlated significantly with that of plasma (p<0.001). A high prevalence of overweight and obesity was found in the study population with a mean BMI of 27.5 (26.0-29.0) kg/m2. Both BMI and waist circumference were positively associated with several adipokines (resistin, adipsin, lipocalin-2, PAI-1 and leptin) and with insulin and suPAR. However, these anthropometric measures were not associated with established biomarkers of inflammation (CRP, MCP-1, TNFα, IL-1β, IL-6, and IL-8). Hypertension was significantly more common in obese compared to normal weight patients (p<0.01), and could be independently predicted by leptin, insulin and suPAR. During the two months period from pre- to post-surgery there was a significant reduction in body weight, BMI, waist circumference and waist-hip ratio.
Conclusions: We confirm the association between CRC and obesity and find an association between obesity, adipokines, insulin and suPAR. However, we do not find a link between obesity and inflammation with regards to the inflammatory markers measured. Although most CRC patients experienced weight loss during the postoperative period, these changes were not correlated with changes in physical function. Our work also adds suPAR to the growing panel of diagnostically valuable analytes validated in DBS samples, and report for the first time on an association between suPAR and diagnosed hypertension. | eng |