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The study aimed to identify single-nucleotide variants (SNVs) on pigmentation-related genes with importance in risk and clinicopathological aspects of CM. The study was conducted in two stages. In stage 1, 103 CM patients and 103 controls were analyzed using Genome-Wide Human SNV Arrays in order to identify SNVs in pigmentation-related genes, and the most important SNVs were selected for data validation in stage 2 by real-time polymerase-chain reaction in 247 CM patients and 280 controls. <jats:italic>ADCY3<\/jats:italic> c.675+9196T&gt;G, <jats:italic>CREB1<\/jats:italic> c.303+373G&gt;A, and <jats:italic>MITF<\/jats:italic> c.938-325G&gt;A were selected for data validation among 74 SNVs. Individuals with <jats:italic>CREB1<\/jats:italic> GA or AA genotype and allele \u201cA\u201d were under 1.79 and 1.47-fold increased risks of CM than others, respectively. Excesses of <jats:italic>CREB1<\/jats:italic> AA and <jats:italic>MITF<\/jats:italic> AA genotype were seen in patients with tumors at Clark levels III to V (27.8% versus 13.7%) and at III or IV stages (46.1% versus 24.9%) compared to others, respectively. When compared to others, patients with <jats:italic>ADCY3<\/jats:italic> TT had 1.89 more chances of presenting CM progression, and those with <jats:italic>MITF<\/jats:italic> GA or AA had 2.20 more chances of evolving to death by CM. Our data provide, for the first time, preliminary evidence that inherited abnormalities in <jats:italic>ADCY3<\/jats:italic>, <jats:italic>CREB1<\/jats:italic>, and <jats:italic>MITF<\/jats:italic> pigmentation-related genes, not only can increase the risk to CM, but also influence CM patients\u2019 clinicopathological features.<\/jats:p>","DOI":"10.1038\/s41598-020-68945-9","type":"journal-article","created":{"date-parts":[[2020,7,22]],"date-time":"2020-07-22T10:04:54Z","timestamp":1595412294000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Inherited variations in human pigmentation-related genes modulate cutaneous melanoma risk and clinicopathological features in Brazilian population"],"prefix":"10.1038","volume":"10","author":[{"given":"Gustavo Jacob","family":"Louren\u00e7o","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristiane","family":"Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benilton S\u00e1","family":"Carvalho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Torricelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet Keller","family":"Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela Vilas B\u00f4as","family":"Gomez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Augusto","family":"Rinck-Junior","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wesley Lima","family":"Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinicius Lima","family":"Vazquez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio Vicente","family":"Serrano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aparecida Machado","family":"Moraes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen Silvia Passos","family":"Lima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,7,22]]},"reference":[{"key":"68945_CR1","doi-asserted-by":"publisher","first-page":"15003","DOI":"10.1038\/nrdp.2015.3","volume":"1","author":"D Schadendorf","year":"2015","unstructured":"Schadendorf, D. et al. 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