Associations of serum cytokines and chemokines with the risk of incident cancer in a prospective rheumatoid arthritis cohort.

OBJECTIVES

We aimed to assess whether serum cytokine/chemokine concentrations predict incident cancer in RA patients.

METHODS

Data from cancer-free enrollees in the Veterans Affairs Rheumatoid Arthritis (VARA) Registry were linked to a national VA oncology database and the National Death Index (NDI) to identify incident cancers. Seventeen serum cytokines/chemokines were measured from enrollment serum and an overall weighted cytokine/chemokine score (CK score) was calculated. Associations of cytokines/chemokines with all-site, lung, and lymphoproliferative cancers were assessed in Cox regression models accounting for relevant covariates including age, sex, RA disease activity, and smoking.

RESULTS

In 1216 patients, 146 incident cancers (42 lung and 23 lymphoproliferative cancers) occurred over 10,072 patient-years of follow-up with a median time of 4.6 years from enrollment (cytokine/chemokine measurement) to cancer incidence. In fully adjusted models, CK score was associated with a higher risk of all-site (aHR 1.32, 95% CI 1.01-1.71, p < 0.001), lung (aHR 1.81, 1.40-2.34, p = 0.001), and lung/lymphoproliferative (aHR 1.54 [1.35-1.75], p < 0.001) cancer. The highest quartile of CK score was associated with a higher risk of all-site (aHR 1.91, 0.96-3.81, p = 0.07; p-trend = 0.005), lung (aHR 8.18, 1.63-41.23, p = 0.01; p-trend < 0.001), and lung/lymphoproliferative (aHR 4.56 [1.84-11.31], p = 0.001; p-trend < 0.001) cancer. Thirteen of 17 individual analytes were associated with incident cancer risk.

CONCLUSION

Elevated cytokine/chemokine concentrations are predictive of future cancer in RA patients, particularly lung and lymphoproliferative cancers. These results suggest that the measurement of circulating cytokines/chemokines could be informative in cancer risk stratification and could provide insight into future cancer prevention strategies in RA, and possibly individuals without RA.