Cutaneous phenotype and MC1R variants as modifying factors for the development of melanoma in CDKN2A G101W mutation carriers from 4 countries

Alisa M. Goldstein, Valerie Chaudru, Paola Ghiorzo, Celia Badenas, Josep Malvehy, Lorenza Pastorino, Karine Laud, Benjamin Hulley, Marie Francoise Avril, Joan A. Puig-Butille, Annie Miniere, Rosa Marti, Agnes Chompret, Francisco Cuellar, Isabel Kolm, Montserrat Mila, Margaret A. Tucker, Florence Demenais, Giovanna Bianchi-Scarra, Susana PuigBrigitte Bressac De-Paillerets

Research output: Contribution to journalArticle


The G101W founder mutation is the most common CDKN2A 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 MC1R variants in cases differed significantly across study groups because 12% of Italian melanoma patients had ≥2 MC1R variants vs. >50% for the other case groups. Several MC1R 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-case families, the number and type of MC1R variants varied significantly between multiple-primary-melanoma and single-primary-melanoma patients from the 4 groups; there was also a significant decrease in median age at melanoma diagnosis as the number or type of MC1R variants increased. The variation in the effects of the cutaneous phenotypic and MC1R factors across the study sample suggests that these factors differentially contribute to development of melanoma even on a common genetic background of a germline CDKN2A mutation. Differences in melanoma risk across geographic regions justify the need for individual studies in each country before counseling should be considered.

Original languageEnglish
Pages (from-to)825-831
Number of pages7
JournalInternational Journal of Cancer
Issue number4
Publication statusPublished - Aug 15 2007



  • CDKN2A
  • G101W
  • MC1R
  • Melanoma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Goldstein, A. M., Chaudru, V., Ghiorzo, P., Badenas, C., Malvehy, J., Pastorino, L., Laud, K., Hulley, B., Avril, M. F., Puig-Butille, J. A., Miniere, A., Marti, R., Chompret, A., Cuellar, F., Kolm, I., Mila, M., Tucker, M. A., Demenais, F., Bianchi-Scarra, G., ... De-Paillerets, B. B. (2007). Cutaneous phenotype and MC1R variants as modifying factors for the development of melanoma in CDKN2A G101W mutation carriers from 4 countries. International Journal of Cancer, 121(4), 825-831.