The Metabolic Syndrome, Inflammation, and Colorectal Cancer Risk: An Evaluation of Large Panels of Plasma Protein Markers Using Repeated, Prediagnostic Samples

Abstract

Metabolic syndrome (MetS), a set of metabolic risk factors including obesity, dysglycemia, and dyslipidemia, is associated with increased colorectal cancer (CRC) risk. A putative biological mechanism is chronic, low-grade inflammation, both a feature of MetS and a CRC risk factor. However, excess body fat also induces a proinflammatory state and increases CRC risk. In order to explore the relationship between MetS, body size, inflammation, and CRC, we studied large panels of inflammatory and cancer biomarkers. We included 138 participants from the Västerbotten Intervention Programme with repeated sampling occasions, 10 years apart. Plasma samples were analyzed for 178 protein markers by proximity extension assay. To identify associations between plasma protein levels and MetS components, linear mixed models were fitted for each protein. Twelve proteins were associated with at least one MetS component, six of which were associated with MetS score. MetS alone was not related to any protein. Instead, BMI displayed by far the strongest associations with the biomarkers. One of the 12 MetS score-related proteins (FGF-21), also associated with BMI, was associated with an increased CRC risk (OR 1.71, 95% CI 1.19–2.47). We conclude that overweight and obesity, acting through both inflammation and other mechanisms, likely explain the MetS-CRC connection.

Plasma levels of the proprotein convertase furin and incidence of diabetes and mortality

“…Consistent with our results, in a recent study of 138 participants from the V€ asterbotten Intervention Programme, a positive association between plasma furin levels and BMI was established [9]. We also identified a positive association between plasma furin levels and plasma concentrations of glucose, insulin and LDL-C and a negative association with HDL-C.…”

“…Furthermore, it is established that furin is partially shed from most cells [17]. Plasma furin concentration has also recently been measured in healthy individuals in two small studies [9,18]. Here, we were able to measure furin levels in the circulation in a large number of individuals from a middleaged general population.…”

“…An association between a polymorphism in the furin gene and decreased triglycerides and increased high-density lipoprotein cholesterol (HDL-C) serum concentration was recently established [8]. Moreover, in a recent epidemiological study, elevated circulating furin levels were demonstrated to be associated with a score for the metabolic syndrome as well as with increased BMI and blood triglyceride concentration [9]. However, there is limited knowledge about the role of furin in the development of DM and risk of premature mortality.…”

Circulating levels of inflammatory markers and DNA methylation, an analysis of repeated samples from a population based cohort

“…Sixty-nine men and 51 women with two measurements, taken approximately 10 years apart, were included in the study ( Table 1). The study population was originally selected as part of a project investigating biomarkers for risk prediction and early detection of colorectal cancer, as previously described [11]. Thirty-one participants (26%) were current smokers at baseline.…”

Mucin 16 and kallikrein 13 as potential prognostic factors in colon cancer: Results of an oncological 92-multiplex immunoassay

“…9 Furthermore, by means of Olink technology, metabolic syndrome patients with low levels of hepatocyte growth factor and endothelial cell-specific molecule-1 carried an increased risk of developing CRC. 10 Thus, in this study, we aimed to screen for biomarkers that can be used to evaluate CC prognosis using the Proseek Multiplex Oncology II panel.…”