Conflict of interest The research at the Melanoma Unit in Barcelona is partially funded by Grants 03/0019, 05/0302, 06/0265 and 09/1393 from Fondo de Investigaciones Sanitarias, Spain; by the CIBER de Enfermedades Raras of the Instituto de Salud Carlos III, Spain; by the AGAUR 2009 SGR 1337 of the Catalan Government, Spain and by the National Cancer Institute (NCI) of the US National Institute of Health (NIH) (CA83115).
Genetic variations of patients with familial or multiple melanoma in Southern Brazil
Article first published online: 23 MAY 2012
© 2012 The Authors. Journal of the European Academy of Dermatology and Venereology © 2012 European Academy of Dermatology and Venereology
Journal of the European Academy of Dermatology and Venereology
Volume 27, Issue 2, pages e179–e185, February 2013
How to Cite
Grazziotin, T.C., Rey, M.C.W., Bica, C.G., Pinto, L.A., Bonamigo, R.R., Puig-Butille, J.A., Cuellar, F. and Puig, S. (2013), Genetic variations of patients with familial or multiple melanoma in Southern Brazil. Journal of the European Academy of Dermatology and Venereology, 27: e179–e185. doi: 10.1111/j.1468-3083.2012.04567.x
Funding sources The work was part of the project GenoMEL founded by the European Commission under the 6th Framework Programme, Contract nº: LSHC-CT-2006-018702.
- Issue published online: 22 JAN 2013
- Article first published online: 23 MAY 2012
- Received: 4 January 2012; Accepted: 18 April 2012
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.