{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T18:58:36Z","timestamp":1788893916908,"version":"build-2803163510"},"reference-count":36,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2007,3,30]],"date-time":"2007-03-30T00:00:00Z","timestamp":1175212800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2007,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The G101W founder mutation is the most common <jats:italic>CDKN2A<\/jats:italic> mutation in Italy, Spain, and France. As the background of modifying genes, environmental exposures, and sun behavior vary across countries, studying G101W carriers from distinct countries offers a unique opportunity to evaluate possible modifying factors in melanoma development. We evaluated 76 G101W cases and 59 carrier controls from France, Italy, Spain, and the United States. Hair color and dysplastic nevi distributions differed significantly in cases and controls across the 4 study groups. Cases also varied significantly for eye color, freckling, and nevi. The distribution of <jats:italic>MC1R<\/jats:italic> variants in cases differed significantly across study groups because 12% of Italian melanoma patients had \u22652 <jats:italic>MC1R<\/jats:italic> variants <jats:italic>vs<\/jats:italic>. &gt;50% for the other case groups. Several <jats:italic>MC1R<\/jats:italic> covariates showed significant associations with melanoma risk in all groups combined and in the American, French, and Spanish samples; no significant findings were observed in the Italian sample. In multiple\u2010case families, the number and type of <jats:italic>MC1R<\/jats:italic> variants varied significantly between multiple\u2010primary\u2010melanoma and single\u2010primary\u2010melanoma patients from the 4 groups; there was also a significant decrease in median age at melanoma diagnosis as the number or type of <jats:italic>MC1R<\/jats:italic> variants increased. The variation in the effects of the cutaneous phenotypic and <jats:italic>MC1R<\/jats:italic> factors across the study sample suggests that these factors differentially contribute to development of melanoma even on a common genetic background of a germline <jats:italic>CDKN2A<\/jats:italic> mutation. Differences in melanoma risk across geographic regions justify the need for individual studies in each country before counseling should be considered. \u00a9 2007 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.22712","type":"journal-article","created":{"date-parts":[[2007,3,30]],"date-time":"2007-03-30T20:45:27Z","timestamp":1175287527000},"page":"825-831","source":"Crossref","is-referenced-by-count":42,"title":["Cutaneous phenotype and <i>MC1R<\/i> variants as modifying factors for the development of melanoma in <i>CDKN2A<\/i> G101W mutation carriers from 4 countries"],"prefix":"10.1002","volume":"121","author":[{"given":"Alisa 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