{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T07:25:10Z","timestamp":1789457110463,"version":"build-2803163510"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,9]],"date-time":"2022-03-09T00:00:00Z","timestamp":1646784000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Background and Objective<\/jats:title><jats:p>Growing evidence added to the results from observational studies of lung cancer patients exhibiting eosinophilia. However, whether eosinophils contributed to tumor immune surveillance or neoplastic evolution was unknown. This study aimed to analyze the causal association between eosinophilia and lung cancer.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The causal effect of eosinophil count on lung cancer from a genome-wide association study (GWAS) was investigated using the two-sample Mendelian randomization (MR) method. Secondary results according to different histological subtypes of lung cancer were also implemented. Meanwhile, we compared the measured levels of blood eosinophil counts among different subtypes of lung cancer from real-world data.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The median absolute eosinophilic count (unit: 10<jats:sup>9<\/jats:sup>\/L) [median (min, max): Lung adenocarcinoma 0.7 (0.5, 15); Squamous cell lung cancer 0.7 (0.5, 1.3); Small cell lung cancer 0.7 (0.6, 1.3); <jats:italic>p<\/jats:italic> = 0.96] and the median eosinophil to leukocyte ratio [median (min, max): Lung adenocarcinoma 8.7% (2.1, 42.2%); Squamous cell lung cancer 9.3% (4.1, 17.7%); Small cell lung cancer 8.9% (5.1, 24.1%); <jats:italic>p<\/jats:italic> = 0.91] were similar among different histological subtypes of lung cancer. MR methods indicated that eosinophilia may provide 28% higher risk for squamous cell lung cancer in East Asian [Weighted median method: odds ratio (OR) = 1.28, 95% CI: 1.04\u20131.57, <jats:italic>p<\/jats:italic> = 0.02].<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study suggested that eosinophilia may be a potential causal risk factor in the progression of squamous cell lung cancer in East Asian.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2022.830754","type":"journal-article","created":{"date-parts":[[2022,3,9]],"date-time":"2022-03-09T06:49:56Z","timestamp":1646808596000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Eosinophilia and Lung Cancer: Analysis From Real-World Data and Mendelian Randomization Study"],"prefix":"10.3389","volume":"9","author":[{"given":"Zhufeng","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bigui","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changxing","family":"Ou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuping","family":"Rong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuetao","family":"Kong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangqing","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxing","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1002\/ajh.26352","article-title":"World Health Organization-defined eosinophilic disorders: 2022 update on diagnosis, risk stratification, and management","volume":"97","author":"Shomali","year":"2022","journal-title":"Am J Hematol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1111\/j.1365-2222.2008.02958.x","article-title":"Eosinophils: biological properties and role in health and disease","volume":"38","author":"Hogan","year":"2008","journal-title":"Clin Exp Allergy."},{"key":"B3","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1186\/s12885-020-06966-3","article-title":"Tumor-associated tissue eosinophilia predicts favorable clinical outcome in solid tumors: a meta-analysis","volume":"20","author":"Hu","year":"2020","journal-title":"BMC Cancer."},{"key":"B4","doi-asserted-by":"publisher","first-page":"213","DOI":"10.7326\/0003-4819-35-1-213","article-title":"Marked eosinophilia with cancer: a poor prognostic sign","volume":"35","author":"Brick","year":"1951","journal-title":"Ann Intern Med."},{"key":"B5","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1056\/NEJM198309293091307","article-title":"Pulmonary carcinoma with eosinophilia. demonstration of a tumor-derived eosinophilopoietic factor","volume":"309","author":"Slungaard","year":"1983","journal-title":"N Engl J Med."},{"key":"B6","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1158\/2326-6066.CIR-18-0494","article-title":"Activated eosinophils exert antitumorigenic activities in colorectal cancer","volume":"7","author":"Reichman","year":"2019","journal-title":"Cancer Immunol Res."},{"key":"B7","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1056\/NEJM198309293091310","article-title":"Cancer and eosinophilia","volume":"309","author":"Beeson","year":"1983","journal-title":"N Engl J Med."},{"key":"B8","doi-asserted-by":"publisher","first-page":"893","DOI":"10.7326\/0003-4819-25-6-893","article-title":"Eosinophilia in malignant tumors; its significance","volume":"25","author":"Isaacson","year":"1946","journal-title":"Ann Intern Med."},{"key":"B9","doi-asserted-by":"crossref","DOI":"10.1201\/b18084","volume-title":"Mendelian Randomization: Methods for Using Genetic Variants in Causal Estimation","author":"Burgess","year":"2015"},{"key":"B10","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1093\/ije\/dyh048","article-title":"Commentary: the concept of 'Mendelian Randomization'[J]","volume":"33","author":"Thomas","year":"2004","journal-title":"Int J Epidemiol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"3641","DOI":"10.1093\/hmg\/ddy271","article-title":"GIANT Consortium. 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