{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T11:05:39Z","timestamp":1784199939206,"version":"3.55.0"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100010817","name":"Stiftelsen Kronprinsessan Margaretas Arbetsn\u00e4mnd f\u00f6r Synskadade","doi-asserted-by":"publisher","award":["2025\u2010092"],"award-info":[{"award-number":["2025\u2010092"]}],"id":[{"id":"10.13039\/100010817","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Ocular melanoma (OM) incidence varies worldwide, but the relative impact of geographic latitude versus pigmentation genetics remains debated. We investigated whether the country\u2010level frequency of the rs12913832 derived (G) blue\u2010eye allele (G allele frequency), or latitude better explains international differences in OM incidence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed an observational ecological study of 29 countries using age\u2010standardized OM incidence data from the International Agency for Research on Cancer (IARC), G allele frequencies from publicly available databases, and population\u2010weighted centroids derived from nighttime lights data. We conducted correlation, linear regression, and mediation analyses to assess the associations among latitude, G allele frequency, and OM incidence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In univariate analyses, both latitude and the G allele frequency were positively associated with OM incidence. In multivariate regression, latitude was no longer significant, whereas the G allele frequency explained substantially more variance and uniquely accounted for 61 times more variance (partial\n                      <jats:italic>r<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      ) than latitude. Mediation analysis indicated that about 92% of latitude's effect on incidence was mediated through G allele frequency.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>At the population level, the G allele frequency is a markedly stronger predictor of OM incidence than geographic latitude. As an ecological analysis, this study identifies a population\u2010level association rather than individual\u2010level genetic risk and suggests that pigmentation genetics underlie much of the international variation in OM incidence.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.72038","type":"journal-article","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T04:39:26Z","timestamp":1781239166000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evolutionary Origin of Ocular Melanoma: Associations With rs12913832 G Allele Frequency and Latitude"],"prefix":"10.1002","volume":"15","author":[{"given":"Hans","family":"Witzenhausen","sequence":"first","affiliation":[{"name":"St. Erik Ophthalmic Pathology Laboratory St. Erik Eye Hospital  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hildur","family":"Helgadottir","sequence":"additional","affiliation":[{"name":"Department of Oncology and Pathology Karolinska Institutet  Stockholm Sweden"},{"name":"Theme Cancer Karolinska University Hospital  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"H\u00f6iom","sequence":"additional","affiliation":[{"name":"Department of Oncology and Pathology Karolinska Institutet  Stockholm Sweden"},{"name":"Theme Cancer Karolinska University Hospital  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Olofsson Bagge","sequence":"additional","affiliation":[{"name":"Sahlgrenska Center for Cancer Research, Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy University of Gothenburg  Gothenburg Sweden"},{"name":"Department of Surgery Sahlgrenska University Hospital  Gothenburg Sweden"},{"name":"Wallenberg Centre for Molecular and Translational Medicine University of Gothenburg  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9401-8911","authenticated-orcid":false,"given":"Gustav","family":"St\u00e5lhammar","sequence":"additional","affiliation":[{"name":"St. Erik Ophthalmic Pathology Laboratory St. Erik Eye Hospital  Stockholm Sweden"},{"name":"Department of Clinical Neuroscience, Division of Eye and Vision Karolinska Institutet  Stockholm Sweden"},{"name":"Ocular Oncology Service St. Erik Eye Hospital  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,11]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/(sici)1097\u20100142(19981015)83:8<1664::aid\u2010cncr23>3.0.co;2\u2010g"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.124.1.54"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2008.10.008"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439\u2010007\u20100460\u2010x"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.213"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.128652.111"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep31191"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djab167"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/mss207"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12886"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aao1887"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1316513111"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.64.13.45"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2025.03.002"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0277\u20109536(83)90386\u20106"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12672\u2010022\u201000584\u20100"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/php.12161"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2005.04.020"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010020\u201016276\u20108"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010020\u201015606\u20100"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1562\/2006\u201007\u201017\u2010RA\u2010970"},{"key":"e_1_2_11_23_1","volume-title":"Cancer Incidence in Five Continents","author":"Bray F.","year":"2017"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.20690"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.361"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkr924"},{"key":"e_1_2_11_27_1","volume-title":"The World Factbook 2024","author":"National Foreign Assessment Center (U.S.)","year":"2024"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/35098506"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes13040569"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.104485"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fsigss.2019.09.127"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41597\u2010019\u20100250\u2010z"},{"key":"e_1_2_11_33_1","first-page":"4602003","volume-title":"Ethical Review Act 2003:460","author":"Riksdag TS","year":"2003"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.12\u20109471"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjophthalmol\u20102021\u2010319700"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.3389\/fopht.2024.1414483"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1080\/02713683.2017.1297997"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox11061204"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2024.09.001"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2014.65"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msv256"}],"container-title":["Cancer Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.72038","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cam4.72038","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.72038","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T10:06:17Z","timestamp":1784196377000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cam4.72038"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":40,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1002\/cam4.72038"],"URL":"https:\/\/doi.org\/10.1002\/cam4.72038","archive":["Portico"],"relation":{},"ISSN":["2045-7634","2045-7634"],"issn-type":[{"value":"2045-7634","type":"print"},{"value":"2045-7634","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6]]},"assertion":[{"value":"2025-08-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e72038"}}