{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T10:06:48Z","timestamp":1793873208224,"version":"4.6.1"},"reference-count":53,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2021,10,18]],"date-time":"2021-10-18T00:00:00Z","timestamp":1634515200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2021,10,18]],"date-time":"2021-10-18T00:00:00Z","timestamp":1634515200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["206194"],"award-info":[{"award-number":["206194"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["206194"],"award-info":[{"award-number":["206194"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C98\/A24032"],"award-info":[{"award-number":["C98\/A24032"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C98\/A24032"],"award-info":[{"award-number":["C98\/A24032"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C98\/A24032"],"award-info":[{"award-number":["C98\/A24032"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C98\/A24032"],"award-info":[{"award-number":["C98\/A24032"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C98\/A24032"],"award-info":[{"award-number":["C98\/A24032"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C98\/A24032"],"award-info":[{"award-number":["C98\/A24032"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C98\/A24032"],"award-info":[{"award-number":["C98\/A24032"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C98\/A24032"],"award-info":[{"award-number":["C98\/A24032"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C98\/A24032"],"award-info":[{"award-number":["C98\/A24032"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C98\/A24032"],"award-info":[{"award-number":["C98\/A24032"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C98\/A24032"],"award-info":[{"award-number":["C98\/A24032"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C98\/A24032"],"award-info":[{"award-number":["C98\/A24032"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C98\/A24032"],"award-info":[{"award-number":["C98\/A24032"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C98\/A24032"],"award-info":[{"award-number":["C98\/A24032"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C98\/A24032"],"award-info":[{"award-number":["C98\/A24032"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C98\/A24032"],"award-info":[{"award-number":["C98\/A24032"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C98\/A24032"],"award-info":[{"award-number":["C98\/A24032"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C98\/A24032"],"award-info":[{"award-number":["C98\/A24032"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C98\/A24032"],"award-info":[{"award-number":["C98\/A24032"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C98\/A24032"],"award-info":[{"award-number":["C98\/A24032"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C98\/A24032"],"award-info":[{"award-number":["C98\/A24032"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C98\/A24032"],"award-info":[{"award-number":["C98\/A24032"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C98\/A24032"],"award-info":[{"award-number":["C98\/A24032"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C98\/A24032"],"award-info":[{"award-number":["C98\/A24032"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["RG81771\/84119"],"award-info":[{"award-number":["RG81771\/84119"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C98\/A24032"],"award-info":[{"award-number":["C98\/A24032"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C98\/A24032"],"award-info":[{"award-number":["C98\/A24032"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C98\/A24032"],"award-info":[{"award-number":["C98\/A24032"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C98\/A24032"],"award-info":[{"award-number":["C98\/A24032"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C98\/A24032"],"award-info":[{"award-number":["C98\/A24032"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C98\/A24032"],"award-info":[{"award-number":["C98\/A24032"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C98\/A24032"],"award-info":[{"award-number":["C98\/A24032"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C98\/A24032"],"award-info":[{"award-number":["C98\/A24032"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C98\/A24032"],"award-info":[{"award-number":["C98\/A24032"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C98\/A24032"],"award-info":[{"award-number":["C98\/A24032"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C98\/A24032"],"award-info":[{"award-number":["C98\/A24032"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C98\/A24032"],"award-info":[{"award-number":["C98\/A24032"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C98\/A24032"],"award-info":[{"award-number":["C98\/A24032"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C98\/A24032"],"award-info":[{"award-number":["C98\/A24032"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C98\/A24032"],"award-info":[{"award-number":["C98\/A24032"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C98\/A24032"],"award-info":[{"award-number":["C98\/A24032"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Packard Fellowship"},{"name":"International Agency for Research on Cancer\/World Health Organization","id":[{"id":"https:\/\/ror.org\/01f80g185","id-type":"ROR","asserted-by":"crossref"}]},{"name":"International Agency for Research on Cancer \/ World Health Organisation","id":[{"id":"https:\/\/ror.org\/00v452281","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["206194"],"award-info":[{"award-number":["206194"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"RCUK | Medical Research Council","doi-asserted-by":"publisher","award":["RG84369"],"award-info":[{"award-number":["RG84369"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIHR Cambridge Biomedical Research Centre","id":[{"id":"https:\/\/ror.org\/05m8dr349","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP20ck0106547h0001"],"award-info":[{"award-number":["JP20ck0106547h0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"U.S. Department of Health & Human Services | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["R21CA19165"],"award-info":[{"award-number":["R21CA19165"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"U.S. Department of Health & Human Services | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["R21CA19165"],"award-info":[{"award-number":["R21CA19165"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000879","name":"Alfred P. Sloan Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000879","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Genet"],"published-print":{"date-parts":[[2021,11]]},"DOI":"10.1038\/s41588-021-00928-6","type":"journal-article","created":{"date-parts":[[2021,10,18]],"date-time":"2021-10-18T20:45:35Z","timestamp":1634589935000},"page":"1553-1563","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":183,"title":["Mutational signatures in esophageal squamous cell carcinoma from eight countries with varying incidence"],"prefix":"10.1038","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4904-1041","authenticated-orcid":false,"given":"Sarah","family":"Moody","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5848-005X","authenticated-orcid":false,"given":"Sergey","family":"Senkin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. M. Ashiqul","family":"Islam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0201-2369","authenticated-orcid":false,"given":"Jingwei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dariush","family":"Nasrollahzadeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Cortez Cardoso Penha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Fitzgerald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik N.","family":"Bergstrom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Atkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yudou","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azhar","family":"Khandekar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1932-7463","authenticated-orcid":false,"given":"Karl","family":"Smith-Byrne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Carreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie","family":"Gaborieau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Calli","family":"Latimer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4563-8695","authenticated-orcid":false,"given":"Emily","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Abnizova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pauline E.","family":"Bucciarelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0407-0386","authenticated-orcid":false,"given":"David","family":"Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon W.","family":"Teague","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0980-0587","authenticated-orcid":false,"given":"Behnoush","family":"Abedi-Ardekani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Serra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Yves","family":"Scoazec","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiva","family":"Saffar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farid","family":"Azmoudeh-Ardalan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masoud","family":"Sotoudeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arash","family":"Nikmanesh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hossein","family":"Poustchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmadreza","family":"Niavarani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samad","family":"Gharavi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Eden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Richman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lia S.","family":"Campos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3434-3568","authenticated-orcid":false,"given":"Rebecca C.","family":"Fitzgerald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis Felipe","family":"Ribeiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6742-3708","authenticated-orcid":false,"given":"Sheila Coelho","family":"Soares-Lima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Dzamalala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5550-1916","authenticated-orcid":false,"given":"Blandina Theophil","family":"Mmbaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0477-210X","authenticated-orcid":false,"given":"Tatsuhiro","family":"Shibata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Menya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7538-3582","authenticated-orcid":false,"given":"Alisa M.","family":"Goldstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9820-6335","authenticated-orcid":false,"given":"Reza","family":"Malekzadeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdolreza","family":"Fazel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie","family":"McCormack","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"McKay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Perdomo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghislaine","family":"Scelo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estelle","family":"Chanudet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Humphreys","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludmil B.","family":"Alexandrov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0518-8714","authenticated-orcid":false,"given":"Paul","family":"Brennan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6035-153X","authenticated-orcid":false,"given":"Michael R.","family":"Stratton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,10,18]]},"reference":[{"key":"928_CR1","first-page":"394","volume":"68","author":"F Bray","year":"2018","unstructured":"Bray, F. et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 68, 394\u2013424 (2018).","journal-title":"CA Cancer J. Clin."},{"key":"928_CR2","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1136\/gutjnl-2014-308124","volume":"64","author":"M Arnold","year":"2015","unstructured":"Arnold, M., Soerjomataram, I., Ferlay, J. & Forman, D. Global incidence of oesophageal cancer by histological subtype in 2012. Gut 64, 381\u2013387 (2015).","journal-title":"Gut"},{"key":"928_CR3","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1053\/j.gastro.2017.08.023","volume":"154","author":"CC Abnet","year":"2018","unstructured":"Abnet, C. C., Arnold, M. & Wei, W. Q. Epidemiology of esophageal squamous cell carcinoma. Gastroenterology 154, 360\u2013373 (2018).","journal-title":"Gastroenterology"},{"key":"928_CR4","doi-asserted-by":"publisher","first-page":"2086","DOI":"10.1093\/annonc\/mdx279","volume":"28","author":"G Murphy","year":"2017","unstructured":"Murphy, G. et al. International cancer seminars: a focus on esophageal squamous cell carcinoma. Ann. Oncol. 28, 2086\u20132093 (2017).","journal-title":"Ann. Oncol."},{"key":"928_CR5","doi-asserted-by":"publisher","first-page":"1416","DOI":"10.1053\/j.gastro.2018.12.024","volume":"156","author":"M Sheikh","year":"2019","unstructured":"Sheikh, M. et al. Individual and combined effects of environmental risk factors for esophageal cancer based on results from the Golestan Cohort Study. Gastroenterology 156, 1416\u20131427 (2019).","journal-title":"Gastroenterology"},{"key":"928_CR6","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1002\/ijc.30292","volume":"140","author":"VA McCormack","year":"2017","unstructured":"McCormack, V. A. et al. Informing etiologic research priorities for squamous cell esophageal cancer in Africa: a review of setting-specific exposures to known and putative risk factors. Int. J. Cancer 140, 259\u2013271 (2017).","journal-title":"Int. J. Cancer"},{"key":"928_CR7","doi-asserted-by":"publisher","first-page":"2849","DOI":"10.1007\/s00784-019-02958-1","volume":"23","author":"FW Mello","year":"2019","unstructured":"Mello, F. W. et al. The synergistic effect of tobacco and alcohol consumption on oral squamous cell carcinoma: a systematic review and meta-analysis. Clin. Oral Investig. 23, 2849\u20132859 (2019).","journal-title":"Clin. Oral Investig."},{"key":"928_CR8","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1038\/s41586-020-1943-3","volume":"578","author":"LB Alexandrov","year":"2020","unstructured":"Alexandrov, L. B. et al. The repertoire of mutational signatures in human cancer. Nature 578, 94\u2013101 (2020).","journal-title":"Nature"},{"key":"928_CR9","doi-asserted-by":"publisher","first-page":"1402","DOI":"10.1038\/ng.3441","volume":"47","author":"LB Alexandrov","year":"2015","unstructured":"Alexandrov, L. B. et al. Clock-like mutational processes in human somatic cells. Nat. Genet. 47, 1402\u20131407 (2015).","journal-title":"Nat. Genet."},{"key":"928_CR10","doi-asserted-by":"publisher","first-page":"618","DOI":"10.1126\/science.aag0299","volume":"354","author":"LB Alexandrov","year":"2016","unstructured":"Alexandrov, L. B. et al. Mutational signatures associated with tobacco smoking in human cancer. Science 354, 618\u2013622 (2016).","journal-title":"Science"},{"key":"928_CR11","doi-asserted-by":"publisher","first-page":"1189","DOI":"10.1038\/s41588-020-0692-4","volume":"52","author":"L Riva","year":"2020","unstructured":"Riva, L. et al. The mutational signature profile of known and suspected human carcinogens in mice. Nat. Genet. 52, 1189\u20131197 (2020).","journal-title":"Nat. Genet."},{"key":"928_CR12","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6135","volume":"5","author":"G Scelo","year":"2014","unstructured":"Scelo, G. et al. Variation in genomic landscape of clear cell renal cell carcinoma across Europe. Nat. Commun. 5, 5135 (2014).","journal-title":"Nat. Commun."},{"key":"928_CR13","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1038\/ng.3076","volume":"46","author":"YB Gao","year":"2014","unstructured":"Gao, Y. B. et al. Genetic landscape of esophageal squamous cell carcinoma. Nat. Genet. 46, 1097\u20131102 (2014).","journal-title":"Nat. Genet."},{"key":"928_CR14","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1038\/nature13176","volume":"508","author":"Y Song","year":"2014","unstructured":"Song, Y. et al. Identification of genomic alterations in oesophageal squamous cell cancer. Nature 508, 91\u201395 (2014).","journal-title":"Nature"},{"key":"928_CR15","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1016\/j.ajhg.2015.02.017","volume":"96","author":"L Zhang","year":"2015","unstructured":"Zhang, L. et al. Genomic analyses reveal mutational signatures and frequently altered genes in esophageal squamous cell carcinoma. Am. J. Hum. Genet. 96, 597\u2013611 (2015).","journal-title":"Am. J. Hum. Genet."},{"key":"928_CR16","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.1053\/j.gastro.2016.01.035","volume":"150","author":"G Sawada","year":"2016","unstructured":"Sawada, G. et al. Genomic landscape of esophageal squamous cell carcinoma in a Japanese population. Gastroenterology 150, 1171\u20131182 (2016).","journal-title":"Gastroenterology"},{"key":"928_CR17","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1038\/nature20805","volume":"541","author":"J Kim","year":"2017","unstructured":"Kim, J. et al. Integrated genomic characterization of oesophageal carcinoma. Nature 541, 169\u2013174 (2017).","journal-title":"Nature"},{"key":"928_CR18","doi-asserted-by":"crossref","unstructured":"Chang, J. et al. Genomic analysis of oesophageal squamous-cell carcinoma identifies alcohol drinking-related mutation signature and genomic alterations. Nat. Commun. 8, 15290 (2017).","DOI":"10.1038\/ncomms15290"},{"key":"928_CR19","doi-asserted-by":"publisher","first-page":"938","DOI":"10.1093\/annonc\/mdy011","volume":"29","author":"XC Li","year":"2018","unstructured":"Li, X. C. et al. A mutational signature associated with alcohol consumption and prognostically significantly mutated driver genes in esophageal squamous cell carcinoma. Ann. Oncol. 29, 938\u2013944 (2018).","journal-title":"Ann. Oncol."},{"key":"928_CR20","doi-asserted-by":"publisher","first-page":"1457","DOI":"10.3389\/fonc.2020.01457","volume":"10","author":"KK Mangalaparthi","year":"2020","unstructured":"Mangalaparthi, K. K. et al. Mutational landscape of esophageal squamous cell carcinoma in an Indian cohort. Front. Oncol. 10, 1457 (2020).","journal-title":"Front. Oncol."},{"key":"928_CR21","doi-asserted-by":"publisher","unstructured":"Islam, S. M. A. et al. Uncovering novel mutational signatures by de novo extraction with SigProfilerExtractor. Preprint at bioRxiv https:\/\/doi.org\/10.1101\/2020.12.13.422570 (2020).","DOI":"10.1101\/2020.12.13.422570"},{"key":"928_CR22","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1016\/j.cell.2017.09.042","volume":"171","author":"I Martincorena","year":"2017","unstructured":"Martincorena, I. et al. Universal patterns of selection in cancer and somatic tissues. Cell 171, 1029\u20131041 (2017).","journal-title":"Cell"},{"key":"928_CR23","doi-asserted-by":"publisher","first-page":"1330","DOI":"10.1038\/ng.3670","volume":"48","author":"CD Middlebrooks","year":"2016","unstructured":"Middlebrooks, C. D. et al. Association of germline variants in the APOBEC3 region with cancer risk and enrichment with APOBEC-signature mutations in tumors. Nat. Genet. 48, 1330\u20131338 (2016).","journal-title":"Nat. Genet."},{"key":"928_CR24","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1038\/ng.2955","volume":"46","author":"S Nik-Zainal","year":"2014","unstructured":"Nik-Zainal, S. et al. Association of a germline copy number polymorphism of APOBEC3A and APOBEC3B with burden of putative APOBEC-dependent mutations in breast cancer. Nat. Genet. 46, 487\u2013491 (2014).","journal-title":"Nat. Genet."},{"key":"928_CR25","doi-asserted-by":"crossref","unstructured":"Kidd, J. M., Newman, T. L., Tuzun, E., Kaul, R. & Eichler, E. E. Population stratification of a common APOBEC gene deletion polymorphism. PLoS Genet. 3, e63 (2007).","DOI":"10.1371\/journal.pgen.0030063"},{"key":"928_CR26","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1038\/s41586-020-1969-6","volume":"578","author":"PJ Campbell","year":"2020","unstructured":"Campbell, P. J. et al. Pan-cancer analysis of whole genomes. Nature 578, 82\u201393 (2020).","journal-title":"Nature"},{"key":"928_CR27","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1038\/nature15393","volume":"526","author":"A Auton","year":"2015","unstructured":"Auton, A. et al. A global reference for human genetic variation. Nature 526, 68\u201374 (2015).","journal-title":"Nature"},{"key":"928_CR28","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1093\/hmg\/ddn372","volume":"18","author":"S MacGregor","year":"2009","unstructured":"MacGregor, S. et al. Associations of ADH and ALDH2 gene variation with self report alcohol reactions, consumption and dependence: an integrated analysis. Hum. Mol. Genet. 18, 580\u2013593 (2009).","journal-title":"Hum. Mol. Genet."},{"key":"928_CR29","doi-asserted-by":"publisher","first-page":"1768","DOI":"10.1053\/j.gastro.2009.07.070","volume":"137","author":"R Cui","year":"2009","unstructured":"Cui, R. et al. Functional variants in ADH1B and ALDH2 coupled with alcohol and smoking synergistically enhance esophageal cancer risk. Gastroenterology 137, 1768\u20131775 (2009).","journal-title":"Gastroenterology"},{"key":"928_CR30","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1038\/ng.849","volume":"43","author":"C Wu","year":"2011","unstructured":"Wu, C. et al. Genome-wide association study identifies three new susceptibility loci for esophageal squamous-cell carcinoma in Chinese populations. Nat. Genet. 43, 679\u2013684 (2011).","journal-title":"Nat. Genet."},{"key":"928_CR31","doi-asserted-by":"crossref","unstructured":"Gao, Y. et al. Risk factors for esophageal and gastric cancers in Shanxi Province, China: a case\u2013control study. Cancer Epidemiol. 35, e91\u2013e99 (2011).","DOI":"10.1016\/j.canep.2011.06.006"},{"key":"928_CR32","doi-asserted-by":"publisher","first-page":"1290","DOI":"10.1038\/sj.onc.1210739","volume":"27","author":"MR Akbari","year":"2008","unstructured":"Akbari, M. R. et al. Germline BRCA2 mutations and the risk of esophageal squamous cell carcinoma. Oncogene 27, 1290\u20131296 (2008).","journal-title":"Oncogene"},{"key":"928_CR33","doi-asserted-by":"publisher","first-page":"1042","DOI":"10.1002\/ijc.32619","volume":"146","author":"JMY Ko","year":"2020","unstructured":"Ko, J. M. Y. et al. BRCA2 loss-of-function germline mutations are associated with esophageal squamous cell carcinoma risk in Chinese. Int. J. Cancer 146, 1042\u20131051 (2020).","journal-title":"Int. J. Cancer"},{"key":"928_CR34","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01730-x","volume":"8","author":"J Deng","year":"2017","unstructured":"Deng, J. et al. Comparative genomic analysis of esophageal squamous cell carcinoma between Asian and Caucasian patient populations. Nat. Commun. 8, 1533 (2017).","journal-title":"Nat. Commun."},{"key":"928_CR35","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1126\/science.aau3879","volume":"362","author":"I Martincorena","year":"2018","unstructured":"Martincorena, I. et al. Somatic mutant clones colonize the human esophagus with age. Science 362, 911\u2013917 (2018).","journal-title":"Science"},{"key":"928_CR36","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1038\/s41586-018-0811-x","volume":"565","author":"A Yokoyama","year":"2019","unstructured":"Yokoyama, A. et al. Age-related remodelling of oesophageal epithelia by mutated cancer drivers. Nature 565, 312\u2013317 (2019).","journal-title":"Nature"},{"key":"928_CR37","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1053\/j.gastro.2017.03.033","volume":"153","author":"X Liu","year":"2017","unstructured":"Liu, X. et al. Genetic alterations in esophageal tissues from squamous dysplasia to carcinoma. Gastroenterology 153, 166\u2013177 (2017).","journal-title":"Gastroenterology"},{"key":"928_CR38","doi-asserted-by":"publisher","first-page":"1407","DOI":"10.1016\/S1470-2045(20)30611-2","volume":"21","author":"S Warnakulasuriya","year":"2020","unstructured":"Warnakulasuriya, S. et al. Carcinogenicity of opium consumption. Lancet Oncol. 21, 1407\u20131408 (2020).","journal-title":"Lancet Oncol."},{"key":"928_CR39","doi-asserted-by":"publisher","first-page":"1139","DOI":"10.1038\/s41588-020-00727-5","volume":"52","author":"A Balmain","year":"2020","unstructured":"Balmain, A. The critical roles of somatic mutations and environmental tumor-promoting agents in cancer risk. Nat. Genet. 52, 1139\u20131143 (2020).","journal-title":"Nat. Genet."},{"key":"928_CR40","doi-asserted-by":"publisher","first-page":"3196","DOI":"10.1093\/bioinformatics\/btw389","volume":"32","author":"EA Bergmann","year":"2016","unstructured":"Bergmann, E. A., Chen, B. J., Arora, K., Vacic, V. & Zody, M. C. Conpair: concordance and contamination estimator for matched tumor\u2013normal pairs. Bioinformatics 32, 3196\u20133198 (2016).","journal-title":"Bioinformatics"},{"key":"928_CR41","first-page":"15.10.1","volume":"2016","author":"D Jones","year":"2016","unstructured":"Jones, D. et al. cgpCaVEManWrapper: simple execution of CaVEMan in order to detect somatic single nucleotide variants in NGS data. Curr. Protoc. Bioinformatics 2016, 15.10.1\u201315.10.18 (2016).","journal-title":"Curr. Protoc. Bioinformatics"},{"key":"928_CR42","doi-asserted-by":"publisher","first-page":"15.7.1","DOI":"10.1002\/0471250953.bi1507s52","volume":"52","author":"KM Raine","year":"2015","unstructured":"Raine, K. M. et al. cgpPindel: identifying somatically acquired insertion and deletion events from paired end sequencing. Curr. Protoc. Bioinformatics 52, 15.7.1\u201315.7.12 (2015).","journal-title":"Curr. Protoc. Bioinformatics"},{"key":"928_CR43","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1038\/s41592-018-0051-x","volume":"15","author":"S Kim","year":"2018","unstructured":"Kim, S. et al. Strelka2: fast and accurate calling of germline and somatic variants. Nat. Methods 15, 591\u2013594 (2018).","journal-title":"Nat. Methods"},{"key":"928_CR44","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-019-6041-2","volume":"20","author":"EN Bergstrom","year":"2019","unstructured":"Bergstrom, E. N. et al. SigProfilerMatrixGenerator: a tool for visualizing and exploring patterns of small mutational events. BMC Genomics 20, 685 (2019).","journal-title":"BMC Genomics"},{"key":"928_CR45","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1038\/s43018-020-0027-5","volume":"1","author":"A Degasperi","year":"2020","unstructured":"Degasperi, A. et al. A practical framework and online tool for mutational signature analyses show intertissue variation and driver dependencies. Nat. Cancer 1, 249\u2013263 (2020).","journal-title":"Nat. Cancer"},{"key":"928_CR46","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1038\/nature17676","volume":"534","author":"S Nik-Zainal","year":"2016","unstructured":"Nik-Zainal, S. et al. Landscape of somatic mutations in 560 breast cancer whole-genome sequences. Nature 534, 47\u201354 (2016).","journal-title":"Nature"},{"key":"928_CR47","doi-asserted-by":"publisher","unstructured":"Senkin, S. MSA: reproducible mutational signature attribution with confidence based on simulations. Preprint at bioRxiv https:\/\/doi.org\/10.1101\/2020.12.14.422764 (2020).","DOI":"10.1101\/2020.12.14.422764"},{"key":"928_CR48","doi-asserted-by":"publisher","first-page":"eaaw2872","DOI":"10.1126\/science.aaw2872","volume":"364","author":"R Buisson","year":"2019","unstructured":"Buisson, R. et al. Passenger hotspot mutations in cancer driven by APOBEC3A and mesoscale genomic features. Science 364, eaaw2872 (2019).","journal-title":"Science"},{"key":"928_CR49","doi-asserted-by":"crossref","unstructured":"Bergstrom, E. N., Barnes, M., Martincorena, I. & Alexandrov, L. B. Generating realistic null hypothesis of cancer mutational landscapes using SigProfilerSimulator. BMC Bioinformatics 21, 438 (2020).","DOI":"10.1186\/s12859-020-03772-3"},{"key":"928_CR50","doi-asserted-by":"publisher","first-page":"958","DOI":"10.1038\/s41588-020-0674-6","volume":"52","author":"D Mas-Ponte","year":"2020","unstructured":"Mas-Ponte, D. & Supek, F. DNA mismatch repair promotes APOBEC3-mediated diffuse hypermutation in human cancers. Nat. Genet. 52, 958\u2013968 (2020).","journal-title":"Nat. Genet."},{"key":"928_CR51","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1016\/j.cell.2012.04.024","volume":"149","author":"S Nik-Zainal","year":"2012","unstructured":"Nik-Zainal, S. et al. Mutational processes molding the genomes of 21 breast cancers. Cell 149, 979\u2013993 (2012).","journal-title":"Cell"},{"key":"928_CR52","doi-asserted-by":"publisher","DOI":"10.1186\/s13742-015-0047-8","volume":"4","author":"CC Chang","year":"2015","unstructured":"Chang, C. C. et al. Second-generation PLINK: rising to the challenge of larger and richer datasets. Gigascience 4, 7 (2015).","journal-title":"Gigascience"},{"key":"928_CR53","doi-asserted-by":"publisher","first-page":"1857","DOI":"10.1038\/sj.bjc.6604369","volume":"98","author":"D Nasrollahzadeh","year":"2008","unstructured":"Nasrollahzadeh, D. et al. Opium, tobacco, and alcohol use in relation to oesophageal squamous cell carcinoma in a high-risk area of Iran. Br. J. Cancer 98, 1857\u20131863 (2008).","journal-title":"Br. J. Cancer"}],"container-title":["Nature Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41588-021-00928-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41588-021-00928-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41588-021-00928-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T11:08:50Z","timestamp":1786964930000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41588-021-00928-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,18]]},"references-count":53,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2021,11]]}},"alternative-id":["928"],"URL":"https:\/\/doi.org\/10.1038\/s41588-021-00928-6","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.04.29.21255920","asserted-by":"object"}]},"ISSN":["1061-4036","1546-1718"],"issn-type":[{"value":"1061-4036","type":"print"},{"value":"1546-1718","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,18]]},"assertion":[{"value":"16 December 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 July 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 October 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}]}}