D'Arcy Monica E, Pfeiffer Ruth M, Bradley Marie C, Hoang Phuc H, Tran Thi-Van-Trinh, McElderry John P, Li Mengying, Kebede Michael, DellaValle Curt T, Rivas Sara, Wang Youjin, Gadalla Shahinaz M, Landi Maria Teresa
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Rutgers Center for Pharmacoepidemiology and Treatment Sciences, New Brunswick, NJ, USA.
Nat Commun. 2025 Jun 2;16(1):5095. doi: 10.1038/s41467-025-56803-z.
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.
从不吸烟者肺癌（LCINS）是全球癌症死亡的主要原因之一，但目前尚无针对LCINS的筛查项目。为了确定可作为LCINS风险标志物的医学状况，我们在英国临床实践研究数据链（CPRD-GOLD）中开展了一项巢式病例对照研究，该研究包括1581例LCINS病例和14318例从不吸烟的对照。在索引日期前1至10年与LCINS显著相关的状况在一个独立数据集CPRD-Aurum（2188例LCINS病例，19597例从不吸烟的对照）中得到验证。这些状况包括慢性阻塞性肺疾病/肺气肿（COPD）、胃食管反流病（GERD）、支气管炎和气管炎、1型糖尿病以及胃炎和非感染性肠胃炎及结肠炎。仅对药物使用情况进行调整只会略微减弱这些关联。总体而言，炎症性疾病在LCINS发病机制中似乎很重要，尽管还需要进一步研究来证实这些关联。诸如GERD或COPD等状况可被视为未来LCINS筛查项目纳入标准的一部分。
