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

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.

Fig. 1. Forest plots showing the associations between the medical conditions identified in the 1-10 years prior to selection and lung cancer in individuals who have never smoked.

Data are presented as adjusted odds ratios with 95% confidence intervals from conditional logistic regression models. Estimates in blue are the associations from the discovery (CPRD-GOLD) dataset (1581 LCINS cases and 14,318 never smoking controls), and those in red are the associations in the validation dataset (CPRD-Aurum) (2188 LCINS cases and 19,597 never smoking controls). Source data are provided as a Source Data File.