{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T16:50:19Z","timestamp":1776099019342,"version":"3.50.1"},"reference-count":33,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,1,14]],"date-time":"2021-01-14T00:00:00Z","timestamp":1610582400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Germline variants of the melanocortin\u20101\u2010receptor (<jats:italic>MC1R<\/jats:italic>) gene are the most common genetic trait predisposing to cutaneous melanoma (CM). Here, we performed a literature review and meta\u2010analysis of the association between <jats:italic>MC1R<\/jats:italic> gene variants and the frequency of somatic mutations of the <jats:italic>BRAF, NRAS<\/jats:italic>, and <jats:italic>TERT<\/jats:italic> genes in CM patients. We included studies published until January 2020 in MEDLINE, EMBASE, Ovid Medline, and two grey literature databases. Random effect models were used to pool study\u2010specific estimates into summary odds ratio (SOR) and 95% confidence intervals (CIs). Subgroup and sensitivity analyses were conducted to identify potential sources of heterogeneity and assess the robustness of pooled estimates. Twelve studies published between 2006 and 2018 (encompassing 3566 CM, mostly on nonacral sites) were included. <jats:italic>MC1R<\/jats:italic> gene variants were not significantly associated with the frequency of somatic mutations of the <jats:italic>BRAF<\/jats:italic> and <jats:italic>NRAS<\/jats:italic> genes. Only three studies focused on somatic mutations of the <jats:italic>TERT<\/jats:italic> gene promoter, all of which reported moderate\u2010to\u2010strong positive associations with <jats:italic>MC1R<\/jats:italic> germline variants. <jats:italic>MC1R<\/jats:italic> gene variants appear to make only moderate changes, if any, to the risk of <jats:italic>BRAF\u2010<\/jats:italic> or <jats:italic>NRAS<\/jats:italic>\u2010mutant CM. The association with <jats:italic>TERT<\/jats:italic> promoter mutations is suggestive, yet it warrants confirmation as it is based on a still limited number of studies<\/jats:p>","DOI":"10.1002\/mc.23280","type":"journal-article","created":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T20:01:42Z","timestamp":1610740902000},"page":"167-171","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Germline <i>MC1R<\/i> variants and frequency of somatic <i>BRAF, NRAS<\/i>, and <i>TERT<\/i> mutations in melanoma: Literature review and meta\u2010analysis"],"prefix":"10.1002","volume":"60","author":[{"given":"Ines","family":"Zanna","sequence":"first","affiliation":[{"name":"Cancer Risk Factors and Lifestyle Epidemiology Unit, Institute for Cancer Research Prevention and Clinical Network  Florence Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2262-1102","authenticated-orcid":false,"given":"Saverio","family":"Caini","sequence":"additional","affiliation":[{"name":"Cancer Risk Factors and Lifestyle Epidemiology Unit, Institute for Cancer Research Prevention and Clinical Network  Florence Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Raimondi","sequence":"additional","affiliation":[{"name":"Department of Experimental Oncology, European Institute of Oncology IRCCS  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Calogero","family":"Saieva","sequence":"additional","affiliation":[{"name":"Cancer Risk Factors and Lifestyle Epidemiology Unit, Institute for Cancer Research Prevention and Clinical Network  Florence Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanna","family":"Masala","sequence":"additional","affiliation":[{"name":"Cancer Risk Factors and Lifestyle Epidemiology Unit, Institute for Cancer Research Prevention and Clinical Network  Florence Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Massi","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Section of Pathological Anatomy University of Florence  Florence Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emilia","family":"Cocorocchio","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology of Melanoma, Sarcoma and Rare Tumors, European Institute of Oncology IRCCS  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Queirolo","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology of Melanoma, Sarcoma and Rare Tumors, European Institute of Oncology IRCCS  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ignazio","family":"Stanganelli","sequence":"additional","affiliation":[{"name":"Skin Cancer Unit, Scientific Institute of Romagna for the Study and Treatment of Cancer IRCSS  Meldola Italy"},{"name":"Department of Dermatology University of Parma  Parma Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Gandini","sequence":"additional","affiliation":[{"name":"Department of Experimental Oncology, European Institute of Oncology IRCCS  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,1,14]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.23396"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.29018"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0749.2005.00278.x"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/pcmr.12257"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh043"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2005.03.034"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.2147\/CMAR.S155283"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2016.37"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-017-0424-2"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.05.044"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1229259"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1127515"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2008.67"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2012.385"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2017.10.002"},{"key":"e_1_2_8_17_1","unstructured":"PROSPERO International prospective register of systematic reviews. 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