{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T23:05:44Z","timestamp":1789945544311,"version":"4.0.1"},"reference-count":48,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2016,7,23]],"date-time":"2016-07-23T00:00:00Z","timestamp":1469232000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100006364","name":"Institut National Du Cancer","doi-asserted-by":"publisher","award":["INCa_5982"],"award-info":[{"award-number":["INCa_5982"]}],"id":[{"id":"10.13039\/501100006364","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2016,11]]},"abstract":"<jats:p>Breslow thickness (BT) is a major prognostic factor of cutaneous melanoma (CM), the most fatal skin cancer. The genetic component of BT has only been explored by candidate gene studies with inconsistent results. Our objective was to uncover the genetic factors underlying BT using an hypothesis\u2010free genome\u2010wide approach. Our analysis strategy integrated a genome\u2010wide association study (GWAS) of single nucleotide polymorphisms (SNPs) for BT followed by pathway analysis of GWAS outcomes using the gene\u2010set enrichment analysis (GSEA) method and epistasis analysis within BT\u2010associated pathways. This strategy was applied to two large CM datasets with Hapmap3\u2010imputed SNP data: the French MELARISK study for discovery (966 cases) and the MD Anderson Cancer Center study (1,546 cases) for replication. While no marginal effect of individual SNPs was revealed through GWAS, three pathways, defined by gene ontology (GO) categories were significantly enriched in genes associated with BT (false discovery rate \u22645% in both studies): hormone activity, cytokine activity and myeloid cell differentiation. Epistasis analysis, within each significant GO, identified a statistically significant interaction between <jats:italic>CDC42<\/jats:italic> and <jats:italic>SCIN<\/jats:italic> SNPs (<jats:italic>p<\/jats:italic><jats:sub>meta\u2010int<\/jats:sub> =2.2 \u00d7 10<jats:sup>\u22126<\/jats:sup>, which met the overall multiple\u2010testing corrected threshold of 2.5 \u00d7 10<jats:sup>\u22126<\/jats:sup>). These two SNPs (and proxies) are strongly associated with <jats:italic>CDC42<\/jats:italic> and <jats:italic>SCIN<\/jats:italic> gene expression levels and map to regulatory elements in skin cells. This interaction has important biological relevance since CDC42 and SCIN proteins have opposite effects in actin cytoskeleton organization and dynamics, a key mechanism underlying melanoma cell migration and invasion.<\/jats:p>","DOI":"10.1002\/ijc.30245","type":"journal-article","created":{"date-parts":[[2016,6,27]],"date-time":"2016-06-27T18:36:49Z","timestamp":1467052609000},"page":"2012-2020","source":"Crossref","is-referenced-by-count":10,"title":["A comprehensive genome\u2010wide analysis of melanoma Breslow thickness identifies interaction between <i>CDC42<\/i> and <i>SCIN<\/i> genetic variants"],"prefix":"10.1002","volume":"139","author":[{"given":"Amaury","family":"Vaysse","sequence":"first","affiliation":[{"name":"INSERM Genetic Variation and Human Diseases Unit UMR\u2010946 Paris France"},{"name":"Universit\u00e9 Sorbonne Paris Cit\u00e9 Institut Universitaire d'H\u00e9matologie, Universit\u00e9 Paris Diderot Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenying","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Surgical Oncology the University of Texas MD Anderson Cancer Center Houston TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myriam","family":"Brossard","sequence":"additional","affiliation":[{"name":"INSERM Genetic Variation and Human Diseases Unit UMR\u2010946 Paris France"},{"name":"Universit\u00e9 Sorbonne Paris Cit\u00e9 Institut Universitaire d'H\u00e9matologie, Universit\u00e9 Paris Diderot Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingyi","family":"Wei","sequence":"additional","affiliation":[{"name":"Duke Cancer Institute, Duke University Medical Center and Department of Medicine, Duke University School of Medicine Durham NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei V.","family":"Chen","sequence":"additional","affiliation":[{"name":"Laboratory Informatics System, Department of Clinical Applications &amp; Support the University of Texas M. 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