{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T13:07:21Z","timestamp":1783084041002,"version":"3.54.6"},"reference-count":56,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,3,8]],"date-time":"2024-03-08T00:00:00Z","timestamp":1709856000000},"content-version":"vor","delay-in-days":36,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21K07963"],"award-info":[{"award-number":["21K07963"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Esophageal squamous cell carcinoma (ESCC) is sometimes detected in non\u2010drinker and non\u2010smoker females who are considered to have very low risk of ESCC development in daily practice. This study examined the clinicopathological and genomic characteristics of ESCCs in females with no history of drinking and smoking.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The sample comprised 118 ESCC lesions occurring in 95 female patients who underwent endoscopic submucosal dissection at our department between January 2008 and December 2019. The patients were categorized into two groups: 51 lesions in 49 patients with no history of drinking and smoking (nondrinker\/nonsmoker [NDNS] group) and 69 lesions in 45 patients with a history of drinking or smoking (drinker\/smoker [DS] group). We analyzed the differences in clinicopathological and cancerous genomic characteristics between the groups. Significant genomic alterations were validated using immunohistochemistry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Multiple logistic regression revealed that older age, fewer multiple Lugol\u2010voiding lesions (LVLs), and reflux esophagitis (RE) were independently associated with the occurrence of ESCCs in the NDNS group. ESCC lesions in the NDNS group were predominantly located in the mid\u2010thoracic esophagus, posterior wall side, with 0\u2010IIa, the aspect ratio of the lesion &gt;2 (vertical\/horizontal), and endoscopic keratinization. Genetic analysis showed that <jats:italic>CDKN2A<\/jats:italic> driver alterations were significantly more frequent and <jats:italic>KMT2D<\/jats:italic> alterations were significantly less frequent in the NDNS group than in the DS group. <jats:italic>KMT2D<\/jats:italic> alterations were strongly correlated with immunostaining.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Older nondrinker, nonsmoker females with RE and fewer multiple LVLs may develop longitudinal 0\u2010IIa ESCC with keratinization of the posterior wall of the mid\u2010thoracic esophagus. ESCCs in nondrinker, nonsmoker females had fewer <jats:italic>KMT2D<\/jats:italic> alterations and more <jats:italic>CDKN2A<\/jats:italic> alterations, which may be a biomarker for treatment.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.7078","type":"journal-article","created":{"date-parts":[[2024,3,8]],"date-time":"2024-03-08T15:55:47Z","timestamp":1709913347000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Clinicopathological and genomic features of superficial esophageal squamous cell carcinomas in nondrinker, nonsmoker females"],"prefix":"10.1002","volume":"13","author":[{"given":"Motomitsu","family":"Fukuhara","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Graduate School of Biomedical and Health Sciences, Hiroshima University  Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0942-1541","authenticated-orcid":false,"given":"Yuji","family":"Urabe","sequence":"additional","affiliation":[{"name":"Gastrointestinal Endoscopy and Medicine Hiroshima University Hospital  Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hikaru","family":"Nakahara","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Graduate School of Biomedical and Health Sciences, Hiroshima University  Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Ishikawa","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology Graduate School of Biomedical and Health Sciences, Hiroshima University  Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuki","family":"Ishibashi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Graduate School of Biomedical and Health Sciences, Hiroshima University  Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirona","family":"Konishi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Graduate School of Biomedical and Health Sciences, Hiroshima University  Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junichi","family":"Mizuno","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Graduate School of Biomedical and Health Sciences, Hiroshima University  Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidenori","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Endoscopy Hiroshima University Hospital  Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiyoshi","family":"Tsuboi","sequence":"additional","affiliation":[{"name":"Department of Endoscopy Hiroshima University Hospital  Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Yamashita","sequence":"additional","affiliation":[{"name":"Department of Endoscopy Hiroshima University Hospital  Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichi","family":"Hiyama","sequence":"additional","affiliation":[{"name":"Department of Clinical Research Center Hiroshima University Hospital  Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6369-0641","authenticated-orcid":false,"given":"Hidehiko","family":"Takigawa","sequence":"additional","affiliation":[{"name":"Department of Endoscopy Hiroshima University Hospital  Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Kotachi","sequence":"additional","affiliation":[{"name":"Department of Endoscopy Hiroshima University Hospital  Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Yuge","sequence":"additional","affiliation":[{"name":"Department of Endoscopy Hiroshima University Hospital  Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. 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