BACKGROUND: Patients with familial melanoma or multiple primary melanoma represent a high-risk population to hereditary melanoma. Mutations in susceptibility genes, such as CDKN2A, CDK4 and MC1R, have been associated with the development of melanoma. OBJECTIVES: The purpose of this study was to determine the genotypic background of patients with familial and/or multiple melanoma in southern Brazil. METHODS: This study analysed 33 cases (5 patients with multiple primary melanoma and 28 patients from families with at least two well documented cases) and 29 controls. Genomic analysis of CDKN2A and CDK4 genes by PCR-SSCP analysis and sequencing and direct sequencing of MC1R were performed in all individuals. RESULTS: No functional mutations in CDKN2A or CDK4 were detected in the 62 individuals. Infrequent variants in polymorphic loci of CDKN2A gene were identified in 15 participants (24.2%) and 24/33 (72.8%) cases and 19/27 (70.4%) controls reported at least one infrequent variant in MC1R (P = 0.372). Furthermore, a non-significant tendency towards an association between melanoma risk and MC1R variants G274A and C451T and a non-significant linear tendency to the number of infrequent high-risk variants in MC1R were observed. CONCLUSIONS: These results suggest that in southern Brazilian population, CDKN2A or CDK4 germinal alterations may have a weaker influence than previously thought and environmental risk factors may play a central role in melanoma susceptibility. However, considering the tendency observed for gene MC1R, low-penetrance genes may be a relevant aetiological factor in southern Brazil with fair skin population and high sunlight exposure.
BACKGROUND:Patients with familial melanoma or multiple primary melanoma represent a high-risk population to hereditary melanoma. Mutations in susceptibility genes, such as CDKN2A, CDK4 and MC1R, have been associated with the development of melanoma. OBJECTIVES: The purpose of this study was to determine the genotypic background of patients with familial and/or multiple melanoma in southern Brazil. METHODS: This study analysed 33 cases (5 patients with multiple primary melanoma and 28 patients from families with at least two well documented cases) and 29 controls. Genomic analysis of CDKN2A and CDK4 genes by PCR-SSCP analysis and sequencing and direct sequencing of MC1R were performed in all individuals. RESULTS: No functional mutations in CDKN2A or CDK4 were detected in the 62 individuals. Infrequent variants in polymorphic loci of CDKN2A gene were identified in 15 participants (24.2%) and 24/33 (72.8%) cases and 19/27 (70.4%) controls reported at least one infrequent variant in MC1R (P = 0.372). Furthermore, a non-significant tendency towards an association between melanoma risk and MC1R variants G274A and C451T and a non-significant linear tendency to the number of infrequent high-risk variants in MC1R were observed. CONCLUSIONS: These results suggest that in southern Brazilian population, CDKN2A or CDK4 germinal alterations may have a weaker influence than previously thought and environmental risk factors may play a central role in melanoma susceptibility. However, considering the tendency observed for gene MC1R, low-penetrance genes may be a relevant aetiological factor in southern Brazil with fair skin population and high sunlight exposure.
Authors: Alexandre Leon Ribeiro de Ávila; Ana Cristina Victorino Krepischi; Luciana Facure Moredo; Talita Ferreira Marques Aguiar; Felipe Carneiro da Silva; Bianca Costa Soares de Sá; Amanda França de Nóbrega; Maria Isabel Waddington Achatz; João Pedreira Duprat; Gilles Landman; Dirce Maria Carraro Journal: Fam Cancer Date: 2014-12 Impact factor: 2.375
Authors: Miriam Potrony; Celia Badenas; Paula Aguilera; Joan Anton Puig-Butille; Cristina Carrera; Josep Malvehy; Susana Puig Journal: Ann Transl Med Date: 2015-09
Authors: Susana Puig; Miriam Potrony; Francisco Cuellar; Joan Anton Puig-Butille; Cristina Carrera; Paula Aguilera; Eduardo Nagore; Zaida Garcia-Casado; Celia Requena; Rajiv Kumar; Gilles Landman; Bianca Costa Soares de Sá; Gisele Gargantini Rezze; Luciana Facure; Alexandre Leon Ribeiro de Avila; Maria Isabel Achatz; Dirce Maria Carraro; João Pedreira Duprat Neto; Thais C Grazziotin; Renan R Bonamigo; Maria Carolina W Rey; Claudia Balestrini; Enrique Morales; Montserrat Molgo; Renato Marchiori Bakos; Patricia Ashton-Prolla; Roberto Giugliani; Alejandra Larre Borges; Virginia Barquet; Javiera Pérez; Miguel Martínez; Horacio Cabo; Emilia Cohen Sabban; Clara Latorre; Blanca Carlos-Ortega; Julio C Salas-Alanis; Roger Gonzalez; Zulema Olazaran; Josep Malvehy; Celia Badenas Journal: Genet Med Date: 2015-12-17 Impact factor: 8.822
Authors: Amelia K Smit; Marielys Collazo-Roman; Susan T Vadaparampil; Stella Valavanis; Jocelyn Del Rio; Brenda Soto; Idhaliz Flores; Julie Dutil; Peter A Kanetsky Journal: Sci Rep Date: 2020-04-29 Impact factor: 4.379