Increased plasma soluble uPAR level is a risk marker of respiratory cancer in initially cancer-free individuals

Anne A Langkilde; Tine Willum Hansen; Steen Ladelund; Ove Andersen; Steen Bendix Haugaard; Jorgen Jeppesen; Jesper Eugen-Olsen; Tine Willum Hansen; Allan Linneberg; Jørgen Lykke Jeppesen

doi:10.1158/1055-9965.epi-10-1009

Increased plasma soluble uPAR level is a risk marker of respiratory cancer in initially cancer-free individuals

Anne A Langkilde, Tine Willum Hansen, Steen Ladelund, Ove Andersen, Steen Bendix Haugaard, Jorgen Jeppesen, Jesper Eugen-Olsen, Tine Willum Hansen, Allan Linneberg, Jørgen Lykke Jeppesen

41 Citations (Scopus)

Abstract

Background: 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. Methods: 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. Results: 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, P < 0.001), 0.92 (95% CI: 0.69-1.24, P = 0.59), and 1.33 (95% CI: 1.13-1.58, P < 0.001) of being diagnosed with respiratory, gastrointestinal, and other cancer types, respectively. Conclusion: 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. Impact: 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.

Original language	English
Journal	Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Volume	20
Pages (from-to)	609
DOIs	https://doi.org/10.1158/1055-9965.epi-10-1009
Publication status	Published - Apr 2011

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Langkilde, A. A., Hansen, T. W., Ladelund, S., Andersen, O., Haugaard, S. B., Jeppesen, J., Eugen-Olsen, J., Hansen, T. W., Linneberg, A., & Jeppesen, J. L. (2011). Increased plasma soluble uPAR level is a risk marker of respiratory cancer in initially cancer-free individuals. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 20, 609. https://doi.org/10.1158/1055-9965.epi-10-1009

Increased plasma soluble uPAR level is a risk marker of respiratory cancer in initially cancer-free individuals. / Langkilde, Anne A; Hansen, Tine Willum; Ladelund, Steen et al.
In: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, Vol. 20, 04.2011, p. 609.

Research output: Contribution to journal › Journal article › Research › peer-review

Langkilde, AA, Hansen, TW, Ladelund, S, Andersen, O, Haugaard, SB, Jeppesen, J, Eugen-Olsen, J, Hansen, TW, Linneberg, A & Jeppesen, JL 2011, 'Increased plasma soluble uPAR level is a risk marker of respiratory cancer in initially cancer-free individuals', Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, vol. 20, pp. 609. https://doi.org/10.1158/1055-9965.epi-10-1009

Langkilde AA, Hansen TW, Ladelund S, Andersen O, Haugaard SB, Jeppesen J et al. Increased plasma soluble uPAR level is a risk marker of respiratory cancer in initially cancer-free individuals. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2011 Apr;20:609. doi: 10.1158/1055-9965.epi-10-1009

Langkilde, Anne A ; Hansen, Tine Willum ; Ladelund, Steen et al. / Increased plasma soluble uPAR level is a risk marker of respiratory cancer in initially cancer-free individuals. In: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2011 ; Vol. 20. pp. 609.

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title = "Increased plasma soluble uPAR level is a risk marker of respiratory cancer in initially cancer-free individuals",

abstract = "Background: 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. Methods: 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. Results: 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, P < 0.001), 0.92 (95% CI: 0.69-1.24, P = 0.59), and 1.33 (95% CI: 1.13-1.58, P < 0.001) of being diagnosed with respiratory, gastrointestinal, and other cancer types, respectively. Conclusion: 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. Impact: 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.",

author = "Langkilde, {Anne A} and Hansen, {Tine Willum} and Steen Ladelund and Ove Andersen and Haugaard, {Steen Bendix} and Jorgen Jeppesen and Jesper Eugen-Olsen and Hansen, {Tine Willum} and Allan Linneberg and Jeppesen, {J{\o}rgen Lykke}",

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T1 - Increased plasma soluble uPAR level is a risk marker of respiratory cancer in initially cancer-free individuals

AU - Langkilde, Anne A

AU - Hansen, Tine Willum

AU - Ladelund, Steen

AU - Andersen, Ove

AU - Haugaard, Steen Bendix

AU - Jeppesen, Jorgen

AU - Eugen-Olsen, Jesper

AU - Hansen, Tine Willum

AU - Linneberg, Allan

AU - Jeppesen, Jørgen Lykke

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N2 - Background: 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. Methods: 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. Results: 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, P < 0.001), 0.92 (95% CI: 0.69-1.24, P = 0.59), and 1.33 (95% CI: 1.13-1.58, P < 0.001) of being diagnosed with respiratory, gastrointestinal, and other cancer types, respectively. Conclusion: 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. Impact: 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.

AB - Background: 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. Methods: 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. Results: 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, P < 0.001), 0.92 (95% CI: 0.69-1.24, P = 0.59), and 1.33 (95% CI: 1.13-1.58, P < 0.001) of being diagnosed with respiratory, gastrointestinal, and other cancer types, respectively. Conclusion: 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. Impact: 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.

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DO - 10.1158/1055-9965.epi-10-1009

M3 - Journal article

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SN - 1538-7755

VL - 20

SP - 609

JO - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology

JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology

ER -

Increased plasma soluble uPAR level is a risk marker of respiratory cancer in initially cancer-free individuals

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