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Here, we examine the role of genetic ancestry, skin pigmentation, and sun exposure in Hispanic\/Latinos and non-Hispanic whites on cSCC risk. We observe an increased cSCC risk with greater European ancestry (<jats:italic>P<\/jats:italic>\u2009=\u20091.27\u2009\u00d7\u200910<jats:sup>\u221242<\/jats:sup>) within Hispanic\/Latinos and with greater northern (<jats:italic>P<\/jats:italic>\u2009=\u20092.38\u2009\u00d7\u200910<jats:sup>\u221265<\/jats:sup>) and western (<jats:italic>P<\/jats:italic>\u2009=\u20092.28\u2009\u00d7\u200910<jats:sup>\u221249<\/jats:sup>) European ancestry within non-Hispanic whites. These associations are significantly, but not completely, attenuated after considering skin pigmentation-associated loci, history of actinic keratosis, and sun-protected versus sun-exposed anatomical sites. We also report an association of the well-known pigment variant <jats:italic>Ala111Thr<\/jats:italic> (rs1426654) at <jats:italic>SLC24A5<\/jats:italic> with cSCC in Hispanic\/Latinos. These findings demonstrate a strong correlation of northwestern European genetic ancestry with cSCC risk in both Hispanic\/Latinos and non-Hispanic whites, largely but not entirely mediated through its impact on skin pigmentation.<\/jats:p>","DOI":"10.1038\/s42003-020-01461-8","type":"journal-article","created":{"date-parts":[[2020,12,14]],"date-time":"2020-12-14T11:04:43Z","timestamp":1607943883000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Genetic ancestry, skin pigmentation, and the risk of cutaneous squamous cell carcinoma in Hispanic\/Latino and non-Hispanic white populations"],"prefix":"10.1038","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5829-8191","authenticated-orcid":false,"given":"Eric","family":"Jorgenson","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9839-8667","authenticated-orcid":false,"given":"H\u00e9l\u00e8ne","family":"Choquet","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Yin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6893-4449","authenticated-orcid":false,"given":"Thomas J.","family":"Hoffmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yambazi","family":"Banda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark N.","family":"Kvale","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neil","family":"Risch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2644-055X","authenticated-orcid":false,"given":"Catherine","family":"Schaefer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1582-3475","authenticated-orcid":false,"given":"Maryam M.","family":"Asgari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,12,14]]},"reference":[{"key":"1461_CR1","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1097\/DSS.0000000000000694","volume":"42","author":"TY Loh","year":"2016","unstructured":"Loh, T. 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