Associations of Circulating Cytokines and Chemokines With Cancer Mortality in Men With Rheumatoid Arthritis

Bryant R. England, Jeremy Sokolove, William H. Robinson, Geoffrey M. Thiele, Apar K. Ganti, Harlan Sayles, Kaleb Michaud, Liron Caplan, Lisa A. Davis, Grant W. Cannon, Brian Sauer, Namrata Singh, E. Blair Solow, Andreas M. Reimold, Gail S. Kerr, Pascale Schwab, Josh F. Baker, Ted R. Mikuls

Research output: Contribution to journalArticle

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Abstract

Objective: To examine the potential of circulating cytokines and chemokines as biomarkers of cancer mortality risk in patients with rheumatoid arthritis (RA). Methods: Male participants in the Veterans Affairs RA registry were followed up from the time of enrollment until death or December 2013. Cytokines and chemokines were measured in banked serum obtained at the time of enrollment, using a bead-based multiplex assay, and a previously developed cytokine score was calculated. Vital status and cause of death were determined through the National Death Index. Associations of cytokines with cancer mortality were examined using multivariable competing-risks regression. Results: Among 1,190 men with RA, 60 cancer deaths (30 of which were attributable to lung cancer) occurred over 5,307 patient-years of follow-up. The patients had a mean age of 64.5 years, had established disease (median duration 8.7 years), were seropositive for rheumatoid factor (81%) or anti–cyclic citrullinated peptide antibody (77%), and frequently had a history of smoking (82% current or former). Seven of 17 analytes examined were individually associated with cancer mortality. The cytokine score was associated with overall cancer (subhazard ratio [SHR] 1.42, 95% confidence interval [95% CI] 1.08–1.85) and lung cancer (SHR 1.86, 95% CI 1.57–2.19) mortality in multivariable analyses. Those in the highest quartile of cytokine scores had a >2-fold increased risk of overall cancer mortality (P = 0.039) and a 6-fold increased risk of lung cancer mortality (P = 0.028) relative to the lowest quartile. A synergistic interaction between current smoking and high cytokine score was observed. Conclusion: Serum cytokines and chemokines are associated with cancer and lung cancer mortality in men with RA, independent of multiple factors including age, smoking status, and prevalent cancer.

Original languageEnglish (US)
Pages (from-to)2394-2402
Number of pages9
JournalArthritis and Rheumatology
Volume68
Issue number10
DOIs
StatePublished - Oct 1 2016

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Chemokines
Rheumatoid Arthritis
Cytokines
Mortality
Lung Neoplasms
Neoplasms
Smoking
Confidence Intervals
Rheumatoid Factor
Age Factors
Veterans
Tumor Biomarkers
Serum
Registries
Cause of Death
Peptides
Antibodies

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology

Cite this

England, B. R., Sokolove, J., Robinson, W. H., Thiele, G. M., Ganti, A. K., Sayles, H., ... Mikuls, T. R. (2016). Associations of Circulating Cytokines and Chemokines With Cancer Mortality in Men With Rheumatoid Arthritis. Arthritis and Rheumatology, 68(10), 2394-2402. https://doi.org/10.1002/art.39735

Associations of Circulating Cytokines and Chemokines With Cancer Mortality in Men With Rheumatoid Arthritis. / England, Bryant R.; Sokolove, Jeremy; Robinson, William H.; Thiele, Geoffrey M.; Ganti, Apar K.; Sayles, Harlan; Michaud, Kaleb; Caplan, Liron; Davis, Lisa A.; Cannon, Grant W.; Sauer, Brian; Singh, Namrata; Blair Solow, E.; Reimold, Andreas M.; Kerr, Gail S.; Schwab, Pascale; Baker, Josh F.; Mikuls, Ted R.

In: Arthritis and Rheumatology, Vol. 68, No. 10, 01.10.2016, p. 2394-2402.

Research output: Contribution to journalArticle

England, BR, Sokolove, J, Robinson, WH, Thiele, GM, Ganti, AK, Sayles, H, Michaud, K, Caplan, L, Davis, LA, Cannon, GW, Sauer, B, Singh, N, Blair Solow, E, Reimold, AM, Kerr, GS, Schwab, P, Baker, JF & Mikuls, TR 2016, 'Associations of Circulating Cytokines and Chemokines With Cancer Mortality in Men With Rheumatoid Arthritis', Arthritis and Rheumatology, vol. 68, no. 10, pp. 2394-2402. https://doi.org/10.1002/art.39735
England, Bryant R. ; Sokolove, Jeremy ; Robinson, William H. ; Thiele, Geoffrey M. ; Ganti, Apar K. ; Sayles, Harlan ; Michaud, Kaleb ; Caplan, Liron ; Davis, Lisa A. ; Cannon, Grant W. ; Sauer, Brian ; Singh, Namrata ; Blair Solow, E. ; Reimold, Andreas M. ; Kerr, Gail S. ; Schwab, Pascale ; Baker, Josh F. ; Mikuls, Ted R. / Associations of Circulating Cytokines and Chemokines With Cancer Mortality in Men With Rheumatoid Arthritis. In: Arthritis and Rheumatology. 2016 ; Vol. 68, No. 10. pp. 2394-2402.
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abstract = "Objective: To examine the potential of circulating cytokines and chemokines as biomarkers of cancer mortality risk in patients with rheumatoid arthritis (RA). Methods: Male participants in the Veterans Affairs RA registry were followed up from the time of enrollment until death or December 2013. Cytokines and chemokines were measured in banked serum obtained at the time of enrollment, using a bead-based multiplex assay, and a previously developed cytokine score was calculated. Vital status and cause of death were determined through the National Death Index. Associations of cytokines with cancer mortality were examined using multivariable competing-risks regression. Results: Among 1,190 men with RA, 60 cancer deaths (30 of which were attributable to lung cancer) occurred over 5,307 patient-years of follow-up. The patients had a mean age of 64.5 years, had established disease (median duration 8.7 years), were seropositive for rheumatoid factor (81{\%}) or anti–cyclic citrullinated peptide antibody (77{\%}), and frequently had a history of smoking (82{\%} current or former). Seven of 17 analytes examined were individually associated with cancer mortality. The cytokine score was associated with overall cancer (subhazard ratio [SHR] 1.42, 95{\%} confidence interval [95{\%} CI] 1.08–1.85) and lung cancer (SHR 1.86, 95{\%} CI 1.57–2.19) mortality in multivariable analyses. Those in the highest quartile of cytokine scores had a >2-fold increased risk of overall cancer mortality (P = 0.039) and a 6-fold increased risk of lung cancer mortality (P = 0.028) relative to the lowest quartile. A synergistic interaction between current smoking and high cytokine score was observed. Conclusion: Serum cytokines and chemokines are associated with cancer and lung cancer mortality in men with RA, independent of multiple factors including age, smoking status, and prevalent cancer.",
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T1 - Associations of Circulating Cytokines and Chemokines With Cancer Mortality in Men With Rheumatoid Arthritis

AU - England, Bryant R.

AU - Sokolove, Jeremy

AU - Robinson, William H.

AU - Thiele, Geoffrey M.

AU - Ganti, Apar K.

AU - Sayles, Harlan

AU - Michaud, Kaleb

AU - Caplan, Liron

AU - Davis, Lisa A.

AU - Cannon, Grant W.

AU - Sauer, Brian

AU - Singh, Namrata

AU - Blair Solow, E.

AU - Reimold, Andreas M.

AU - Kerr, Gail S.

AU - Schwab, Pascale

AU - Baker, Josh F.

AU - Mikuls, Ted R.

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N2 - Objective: To examine the potential of circulating cytokines and chemokines as biomarkers of cancer mortality risk in patients with rheumatoid arthritis (RA). Methods: Male participants in the Veterans Affairs RA registry were followed up from the time of enrollment until death or December 2013. Cytokines and chemokines were measured in banked serum obtained at the time of enrollment, using a bead-based multiplex assay, and a previously developed cytokine score was calculated. Vital status and cause of death were determined through the National Death Index. Associations of cytokines with cancer mortality were examined using multivariable competing-risks regression. Results: Among 1,190 men with RA, 60 cancer deaths (30 of which were attributable to lung cancer) occurred over 5,307 patient-years of follow-up. The patients had a mean age of 64.5 years, had established disease (median duration 8.7 years), were seropositive for rheumatoid factor (81%) or anti–cyclic citrullinated peptide antibody (77%), and frequently had a history of smoking (82% current or former). Seven of 17 analytes examined were individually associated with cancer mortality. The cytokine score was associated with overall cancer (subhazard ratio [SHR] 1.42, 95% confidence interval [95% CI] 1.08–1.85) and lung cancer (SHR 1.86, 95% CI 1.57–2.19) mortality in multivariable analyses. Those in the highest quartile of cytokine scores had a >2-fold increased risk of overall cancer mortality (P = 0.039) and a 6-fold increased risk of lung cancer mortality (P = 0.028) relative to the lowest quartile. A synergistic interaction between current smoking and high cytokine score was observed. Conclusion: Serum cytokines and chemokines are associated with cancer and lung cancer mortality in men with RA, independent of multiple factors including age, smoking status, and prevalent cancer.

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