Data from Increased Plasma Soluble uPAR Level Is a Risk Marker of Respiratory Cancer in Initially Cancer-Free Individuals

Abstract

<div>Abstract<p><b>Background:</b> Soluble urokinase plasminogen activator receptor (suPAR) is a stable plasma biomarker associated with inflammation and disease. This study tested the association between suPAR levels and incident respiratory, gastrointestinal, or other types of cancer in initially cancer-free individuals from a general population-based prospective study.</p><p><b>Methods:</b> Baseline plasma samples, baseline characteristics, and follow-up data were available from 2,656 individuals from the population-based Danish MONICA10 (MONItoring trends and determinants of CArdiovascular disease) study, followed for a median of 12.6 years. Cancer was diagnosed according to international classification of diseases (ICD) 8 and ICD-10 codes and suPAR levels were measured using a commercially available ELISA. The association of suPAR levels with incident cancer during follow-up was analyzed using Cox regression, adjusted for established risk factors and the inflammatory markers C-reactive protein (CRP) and leukocyte numbers.</p><p><b>Results:</b> suPAR levels ranged from 0.6 to 22 ng/mL and median suPAR level was 4.01 ng/mL. An increase of 1 ng/mL in baseline suPAR was associated with adjusted HR of 1.61 (95% CI: 1.23–2.11, <i>P</i> < 0.001), 0.92 (95% CI: 0.69–1.24, <i>P</i> = 0.59), and 1.33 (95% CI: 1.13–1.58, <i>P</i> < 0.001) of being diagnosed with respiratory, gastrointestinal, and other cancer types, respectively.</p><p><b>Conclusion:</b> Elevated suPAR levels were associated with increased risk of incident respiratory cancer and other types of cancer, but not gastrointestinal cancers, independently of established risk factors, CRP, and leukocyte numbers.</p><p><b>Impact:</b> These findings suggest that inflammation is involved in cancer development. Risk algorithms based on established risk factors and risk-associated biomarkers should be developed and evaluated in large, general population-based studies. We suggest suPAR as a candidate for evaluation in cancer risk algorithms. <i>Cancer Epidemiol Biomarkers Prev; 20(4); 609–18. ©2011 AACR.</i></p></div>