Journal
INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 97, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.intimp.2021.107719
Keywords
Rheumatoid arthritis; Cancer; Cytokines; Chemokines; Biomarkers; Lung cancer
Categories
Funding
- National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health [R25AA020818-07]
- Rheumatology Research Foundation Scientist Development Award
- National Institute of General Medical Sciences [U54 GM115458]
- Great Plains IDeA-CTR Network
- National Cancer Institute [2P30CA036727-30]
- VA BSRD [I01 BX004676]
- VA BLRD [I01 BX004660]
- Rheumatology Research Foundation
- VA CSRD [I01 CX001703]
- [CX002203]
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Elevated serum cytokine/chemokine concentrations in rheumatoid arthritis (RA) patients are associated with an increased risk of future cancer, particularly lung and lymphoproliferative cancers. These findings suggest that measuring circulating cytokines/chemokines could be informative for cancer risk stratification and future cancer prevention strategies, not only in RA patients but possibly in individuals without RA.
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.
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