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Associations of Circulating Cytokines and Chemokines With Cancer Mortality in Men With Rheumatoid Arthritis
Author(s) -
England Bryant R.,
Sokolove Jeremy,
Robinson William H.,
Thiele Geoffrey M.,
Ganti Apar K.,
Sayles Harlan,
Michaud Kaleb,
Caplan Liron,
Davis Lisa A.,
Can Grant W.,
Sauer Brian,
Singh Namrata,
Blair Solow E.,
Reimold Andreas M.,
Kerr Gail S.,
Schwab Pascale,
Baker Josh F.,
Mikuls Ted R.
Publication year - 2016
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.39735
Subject(s) - medicine , lung cancer , rheumatoid arthritis , cancer , quartile , confidence interval , immunology , oncology
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.