Inflammatory diseases and risk of lung cancer among individuals who have never smoked

Monica E. D’Arcy (), Ruth M. Pfeiffer (), Marie C. Bradley, Phuc H. Hoang, Thi- Van-Trinh Tran, John P. McElderry, Mengying Li, Michael Kebede, Curt T. DellaValle, Sara Rivas, Youjin Wang, Shahinaz M. Gadalla and Maria Teresa Landi ()
Additional contact information
Monica E. D’Arcy: National Cancer Institute
Ruth M. Pfeiffer: National Cancer Institute
Marie C. Bradley: National Cancer Institute
Phuc H. Hoang: National Cancer Institute
Thi- Van-Trinh Tran: National Cancer Institute
John P. McElderry: National Cancer Institute
Mengying Li: National Cancer Institute
Michael Kebede: University of North Carolina
Curt T. DellaValle: National Cancer Institute
Sara Rivas: National Cancer Institute
Youjin Wang: National Cancer Institute
Shahinaz M. Gadalla: National Cancer Institute
Maria Teresa Landi: National Cancer Institute

Nature Communications, 2025, vol. 16, issue 1, 1-12

Abstract: Abstract Lung cancer in never-smokers (LCINS) is a leading cause of cancer death globally, but no screening programs for LCINS exist. To identify medical conditions that could serve as markers of LCINS risk, we conducted a nested case-control study within the United Kingdom’s Clinical Practice Research Datalink (CPRD-GOLD), consisting of 1581 LCINS cases and 14,318 never-smoking controls. Conditions significantly associated with LCINS 1-10 years before the index date were validated in an independent dataset, CPRD-Aurum (2188 LCINS cases, 19,597 never-smoking controls). These conditions include Chronic Obstructive Pulmonary Disease/Emphysema (COPD); gastroesophageal reflux disease (GERD); bronchitis and tracheitis; diabetes mellitus type 1; and gastritis and non-infective gastroenteritis and colitis. Adjusting for medication use only slightly attenuated these associations. Overall, inflammatory diseases appear to be important in LCINS pathogenesis although further studies need to confirm these associations. Conditions such as GERD or COPD could be considered as part of eligibility criteria for future LCINS screening programs.

Date: 2025
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DOI: 10.1038/s41467-025-56803-z

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