Association of Chemerin Plasma Concentration With Risk of Colorectal Cancer

Abstract

Importance: Inflammatory processes have been suggested to have an important role in colorectal cancer (CRC) etiology. Chemerin is a recently discovered inflammatory biomarker thought to exert chemotactic, adipogenic, and angiogenic functions. However, its potential link with CRC has not been sufficiently explored. Objective: To evaluate the prospective association of circulating plasma chemerin concentrations with incident CRC. Design, Setting, and Participants: Prospective case-cohort study based on 27 548 initially healthy participants from the European Prospective Investigation Into Cancer and Nutrition (EPIC)-Potsdam cohort who were followed for up to 16 years. Baseline study information and samples were collected between August 23, 1994, and September 25, 1998. Recruitment was according to random registry sampling from the geographical area of Potsdam, Germany, and surrounding municipalities. The last date of study follow-up was May 10, 2010. Statistical analysis was conducted in 2018. Main Outcomes and Measures: Incident CRC, colon cancer, and rectal cancer. Baseline chemerin plasma concentrations were measured by enzyme-linked immunosorbent assay. Results: A random subcohort of 221 incident CRC cases and 2329 participants free of CRC with available blood sample measurements were included in the analysis. The participants' mean (SD) age was 50 (9) years, 62.1% were female, and 16.5% had a body mass index greater than 30. In multivariable-adjusted Cox proportional hazards regression models taking into account established CRC risk factors, higher chemerin concentrations were associated with a greater risk of CRC, with a hazard ratio (HR) of 1.81 (95% CI, 1.08-3.05; P for trend = .007) for the highest chemerin quartile vs the lowest. Analyses by cancer subsite indicated a stronger association with colon cancer (HR, 2.27; 95% CI, 1.18-4.34 for the highest quartile vs the lowest; P for trend = .005) compared with rectal cancer (HR, 1.27; 95% CI, 0.57-2.85; P for trend = .35). The association was particularly strong for proximal colon cancer (HR, 3.97; 95% CI, 1.51-10.50; P for trend = .001). Conclusions and Relevance: This study found that the association between chemerin concentration and the risk of incident CRC was linear and independent of established CRC risk factors. Further studies are warranted to evaluate chemerin as a novel immune-inflammatory agent in colorectal carcinogenesis.