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Proposed risk factors include male sex, smoking, and RA-associated interstitial lung disease (RA-ILD). However, whether a direct genetic causal link exists between RA-ILD and lung cancer remains unexplored. We used Mendelian randomization with East Asian genetic instruments to evaluate this relationship.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a two-sample Mendelian randomization, in which genetic instruments for RA-ILD were derived from an East Asian genome-wide association study (358 RA-ILD cases and 4550 RA controls), and lung cancer associations were obtained from a cross-ancestry genome-wide association study meta-analysis (20,378 cases, 18,696 controls). Causal effects were estimated using inverse-variance weighted, Mendelian randomization-Egger, and weighted median methods.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Ten single nucleotide polymorphisms were identified as genetic instruments. Inverse-variance weighted analysis revealed no significant causal association between genetically predicted RA-ILD and lung cancer (odds ratio\u2009=\u20091.00; 95% confidence interval: 0.99\u20131.01; P-value\u2009=\u2009.78). Sensitivity analyses showed no horizontal pleiotropy or heterogeneity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings suggest that these severe lung complications of rheumatic arthritis do not inherently share a direct, genetically driven pathway with malignancy. The observed clinical risk may be explained by shared environmental factors, such as smoking or chronic immune dysregulation, rather than inherent genetic pleiotropy, although further investigation is needed to clarify these mechanisms.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/mr\/roag068","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T11:50:20Z","timestamp":1787140220000},"source":"Crossref","is-referenced-by-count":0,"title":["Association between rheumatoid arthritis-interstitial lung disease and lung cancer: A two-sample Mendelian randomization study with East Asian genetic instruments"],"prefix":"10.1093","author":[{"given":"Chueh-Hsuan","family":"Hsu","sequence":"first","affiliation":[{"name":"Graduate Institute of Biomedical Sciences, College of Medicine, China Medical University , Taichung ,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo-Chueh","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital , Taichung ,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9745-1726","authenticated-orcid":false,"given":"Yung-Luen","family":"Yu","sequence":"additional","affiliation":[{"name":"Graduate Institute of Biomedical Sciences, College of Medicine, China Medical University , Taichung ,","place":["Taiwan"]},{"name":"Institute of Translational Medicine and New Drug Development, College of Medicine, China Medical University , Taichung ,","place":["Taiwan"]},{"name":"Center for Molecular Medicine, China Medical University Hospital , Taichung ,","place":["Taiwan"]},{"name":"Office of Research and Development, Asia University , Taichung ,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,8,20]]},"reference":[{"key":"2026090813220283500_ref1","doi-asserted-by":"crossref","first-page":"102776","DOI":"10.1016\/j.autrev.2021.102776","article-title":"Rheumatoid arthritis: extra-articular manifestations and comorbidities","volume":"20","author":"Figus","year":"2021","journal-title":"Autoimmun Rev"},{"key":"2026090813220283500_ref2","doi-asserted-by":"crossref","first-page":"2221","DOI":"10.3899\/jrheum.150166","article-title":"A study of multiple causes of death in rheumatoid arthritis","volume":"42","author":"Pinheiro","year":"2015","journal-title":"J Rheumatol"},{"key":"2026090813220283500_ref3","doi-asserted-by":"crossref","first-page":"2332406","DOI":"10.1080\/07853890.2024.2332406","article-title":"The prevalence and risk factors of rheumatoid arthritis-associated interstitial lung disease: a systematic review and meta-analysis","volume":"56","author":"Wang","year":"2024","journal-title":"Ann Med"},{"key":"2026090813220283500_ref4","doi-asserted-by":"crossref","first-page":"1700","DOI":"10.1136\/annrheumdis-2017-211138","article-title":"A population-based cohort study of rheumatoid arthritis-associated interstitial lung disease: comorbidity and mortality","volume":"76","author":"Hyldgaard","year":"2017","journal-title":"Ann Rheum Dis"},{"key":"2026090813220283500_ref5","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1378\/chest.127.6.2019","article-title":"Histopathologic pattern and clinical features of rheumatoid arthritis-associated interstitial lung disease","volume":"127","author":"Lee","year":"2005","journal-title":"Chest"},{"key":"2026090813220283500_ref6","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1055\/s-0039-1683995","article-title":"Pulmonary complications of rheumatoid arthritis","volume":"40","author":"Farquhar","year":"2019","journal-title":"Semin Respir Crit Care Med"},{"key":"2026090813220283500_ref7","doi-asserted-by":"crossref","first-page":"e44","DOI":"10.1164\/rccm.201807-1255ST","article-title":"Diagnosis of idiopathic pulmonary fibrosis. 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