Background/Purpose: Rheumatoid arthritis (RA) is characterized by chronic inflammation and the dysregulated expression of pro-inflammatory cytokines / chemokines (CK). Chronic inflammation has also been implicated in cancer pathogenesis, particularly through the intercommunication of immune and cancer cells mediated by CK signaling. In this study we sought to test the hypothesis that circulating CKs predict cancer mortality in RA.

Methods: Male participants in the Veterans Affairs RA registry were followed from enrollment until death or December 2013. Using banked serum from enrollment, CKs were measured using a bead-based multiplex assay. CK scores were calculated from individual CKs. Both CK scores and individual CKs were examined in quartiles and as log transformed values. Vital status and cause of death were determined through the National Death Index. Associations of CK score and individual CKs with cancer mortality were examined using multivariable competing-risks regression adjusting for age, race, smoking status, body mass index, comorbidity, visit frequency, nodules, RF concentration, enrollment DAS-28, baseline DMARDs and prednisone use.

Results: There were 1,294 RA patients included with 71 cancer deaths occurring over 5,585 patient-years of follow-up. Patients were older (mean 65 ± 11 years), had established disease (mean 12 ± 12 years), were seropositive for RF (80%) or anti-CCP antibody (77%), and had frequent smoking history (82% current or former). Lung cancer was the most common cause of cancer deaths (n = 30, 42%), followed by leukemia (n = 7) and lymphoma (n = 6). Adjusted associations of CK score with overall and lung cancer mortality are shown in Table 1. After MV adjustment, log-transformed CK score was associated with mortality from all cancers (HR 1.65, 95% CI 1.40 to 1.94, P < 0.001) and lung cancer (HR 1.81, 95% CI 1.47 to 2.22, P < 0.001). Fifteen of the 17 CK analytes examined were associated with cancer mortality after multivariable adjustment. In sub-analyses, excluding those with prevalent cancer at enrollment (n=190), CK score remained associated with overall cancer mortality (HR 3.82, 95% CI 2.19-6.65, P < 0.001 for highest quartile vs. lowest; P trend < 0.001) and lung cancer mortality (HR 9.47, 95% CI 0.85-105.90, P = 0.068 for highest quartile vs. lowest; P trend = 0.001).

Conclusion: Circulating CK concentrations are strongly associated with future cancer mortality in men with RA, an association that is independent of multiple factors including RA disease activity and medications. In addition to highlighting the potential value of CK as a predictive biomarker, these findings suggest that CK expression could act as a crucial link between RA and cancer. Further studies are needed to investigate the role of specific CKs in cancer development and the impact that therapies targeting CKs could yield in reducing cancer burden in RA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/circulating-cytokinechemokine-concentrations-predict-cancer-mortality-in-men-with-rheumatoid-arthritis/