The Risk of Lung Cancer in Rheumatoid Arthritis and Rheumatoid Arthritis–Associated Interstitial Lung Disease - Article

Sep 21, 2026

Evaluate lung cancer risk in rheumatoid arthritis (RA) and RA-associated interstitial lung disease (RA-ILD) using a retrospective, matched cohort study in the Veterans Health Administration from 2000–2019. RA cases were matched up to 1:10 on age, gender, and VA enrollment year to non-RA individuals and analyzed with conditional Cox regression adjusting for race, ethnicity, smoking, Agent Orange exposure, and comorbidities. RA showed an elevated lung cancer hazard, with higher risk in prevalent RA-ILD and persistent associations in sensitivity analyses. Results support targeted surveillance in RA-ILD to reduce cancer-mortality burden.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages9

Reading Time23 min

AccessFree to download

Objective

Methods

Study design and matching

Outcome ascertainment and statistical analysis

Results

Conclusion

Introduction

Arthritis & Rheumatology Vol. 76, No. 12, December 2024, pp 1730–1738 DOI 10.1002/art.42961 Published 2024 . This article is a U.S. Government work and is in the public domain in the USA. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. The Risk of Lung Cancer in Rheumatoid Arthritis and Rheumatoid Arthritis–Associated Interstitial Lung Disease Rebecca T. Brooks,1 Brent Luedders,2 Austin Wheeler,2 Tate M. Johnson,2 Yangyuna Yang,2 Punyasha Roul,2 Apar Kishor Ganti,2 Namrata Singh,3 Brian C. Sauer,4 Grant W. Cannon,4 Joshua F. Baker,5 Ted R. Mikuls,2 and Bryant R. England2 Objective. We aimed to evaluate lung cancer risk in patients with rheumatoid arthritis (RA) and RA-interstitial lung disease (ILD) . Methods. We performed a retrospective, matched cohort study of RA and RA-ILD within the Veterans Health Administration (VA) between 2000 and 2019 . Patients with RA and RA-ILD were identiﬁed with validated administrative-based algorithms, then matched (up to 1:10) on age, gender, and VA enrollment year to individuals without RA. Lung cancers were identiﬁed from a VA oncology database and the National Death Index. Conditional Cox regression models assessed lung cancer risk adjusting for race, ethnicity, smoking status, Agent Orange exposure, and comorbidity burden among matched individuals. Several sensitivity analyses were performed. Results. We matched 72,795 patients with RA with 633,937 patients without RA (mean age 63 years; 88% male) . Over 4,481,323 patient-years, 17,099 incident lung cancers occurred. RA was independently associated with an increased lung cancer risk (adjusted hazard ratio [aHR] 1.58 [95% conﬁdence interval (CI) 1.52–1.64]), which persisted in never smokers (aHR 1 .65 [95% CI 1 .22–2.24]) and in those with incident RA (aHR 1 .54 [95% CI 1 .44–1.65]) . Compared to non-RA controls, prevalent RA-ILD (n = 757) was more strongly associated with lung cancer risk (aHR 3.25 [95% CI 2.13–4.95]) than RA without ILD (aHR 1.57 [95% CI 1.51–1.64]) . Analyses of both prevalent and incident RAILD produced similar results (RA-ILD vs non-RA aHR 2 .88 [95% CI 2 .45–3.40]) . Conclusion. RA was associated with a >50% increased risk of lung cancer, and those with RA-ILD represented a particularly high-risk group with an approximate three-fold increased risk. Increased lung cancer surveillance in RA, and especially RA-ILD, may be a useful strategy for reducing the burden posed by the leading cause of cancer death. INTRODUCTION Rheumatoid arthritis (RA) is a systemic autoimmune disease primarily manifesting as an inﬂammatory arthritis that can result in extra-articular manifestations, particularly in the lungs.1 Interstitial lung disease (ILD) clinically affects approximately 10% of The views expressed in this article are those of the authors and do not necessarily reﬂect the position or policy of the US Department of Veterans Affairs (VA) or the United States government. Dr Johnson’s work was supported by the Rheumatology Research Foundation. Dr Ganti’s work was supported by the VA Biomedical Laboratory Research and Development (BLRD) (grant I01-BX-004676) and the VA Lung Precision Oncology Program (grant I50-CU-000163-01) . Dr Singh’s work was supported by the Rheumatology Research Foundation and the American Heart Association. Dr Baker’s work was supported by the VA Clinical Science Research and Development (CSRD) (grant I01-CX-001703) . Dr Mikuls’ work was supported by the VA BLRD (grants I01-BX-004660 and I01-BX-003635), the Department of Defense (grant PR200793), the Rheumatology Research Foundation, and the National Institute of General Medical Sciences (grant U54-GM-115458) .

FAQs

What was the objective of the study?

To evaluate lung cancer risk in patients with rheumatoid arthritis (RA) and RA-associated interstitial lung disease (RA-ILD).

How was lung cancer risk assessed in the methods?

Through a retrospective, matched cohort study with conditional Cox regression, adjusting for race, ethnicity, smoking status, Agent Orange exposure, and comorbidity burden, using oncology and death index sources for identification.

What did the results show about RA and RA-ILD?

RA was independently associated with increased lung cancer risk, and RA-ILD showed a stronger association, with a particularly high-risk group and persistent findings in sensitivity analyses.

Sep 21, 2026

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