A Customized Pigmentation SNP Array Identifies a Novel SNP Associated with Melanoma Predisposition in the SLC45A2 Gene

Autor: Beatriz Casado, Rafael Botella-Estrada, José A. Avilés, P. Lázaro, Eduardo Nagore, Ana Sánchez-Diez, Carlos Valdes, J. L. Diaz-Perez, Lara P. Fernández, Conrado Martinez-Cadenas, Angel Pizarro, Ana Pitarch, Aintzane Asumendi, Sánchez-Motilla Jm, Enrique Boldo, Francisca Valcuende-Cavero, Javier Benitez, G. Carretero, Matías Mayor, Rafael Lozoya, Gorka Pérez-Yarza, Gloria Ribas, Ana Lluch, Iñigo Martinez de Lizarduy, Gemma Perez-Pastor, M. Dolores Boyano, Maider Ibarrola-Villava, Arantxa Torrijos-Aguilar, Guillermo Pita, Neskuts Izagirre, Yoana Arroyo-Berdugo, Jesús Gardeazabal, Concepción de la Rúa, Manuel Martin-Gonzalez, Cristina Gómez-Fernández, Gloria Tomas-Cabedo, Maria Peña-Chilet, Gerard Pitarch, Mariano Casado, Santos Alonso
Rok vydání: 2011
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Zdroj: Addi. Archivo Digital para la Docencia y la Investigación
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PLoS One
r-FISABIO. Repositorio Institucional de Producción Científica
PLoS ONE, Vol 6, Iss 4, p e19271 (2011)
PLoS ONE
r-FISABIO: Repositorio Institucional de Producción Científica
Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
ISSN: 1932-6203
Popis: 10 p. As the incidence of Malignant Melanoma (MM) reflects an interaction between skin colour and UV exposure, variations in genes implicated in pigmentation and tanning response to UV may be associated with susceptibility to MM. In this study, 363 SNPs in 65 gene regions belonging to the pigmentation pathway have been successfully genotyped using a SNP array. Five hundred and ninety MM cases and 507 controls were analyzed in a discovery phase I. Ten candidate SNPs based on a p-value threshold of 0.01 were identified. Two of them, rs35414 (SLC45A2) and rs2069398 (SILV/CKD2), were statistically significant after conservative Bonferroni correction. The best six SNPs were further tested in an independent Spanish series (624 MM cases and 789 controls). A novel SNP located on the SLC45A2 gene (rs35414) was found to be significantly associated with melanoma in both phase I and phase II (P < 0.0001). None of the other five SNPs were replicated in this second phase of the study. However, three SNPs in TYR, SILV/CDK2 and ADAMTS20 genes (rs17793678, rs2069398 and rs1510521 respectively) had an overall p-value < 0.05 when considering the whole DNA collection (1214 MM cases and 1296 controls). Both the SLC45A2 and the SILV/CDK2 variants behave as protective alleles, while the TYR and ADAMTS20 variants seem to function as risk alleles. Cumulative effects were detected when these four variants were considered together. Furthermore, individuals carrying two or more mutations in MC1R, a well-known low penetrance melanoma-predisposing gene, had a decreased MM risk if concurrently bearing the SLC45A2 protective variant. To our knowledge, this is the largest study on Spanish sporadic MM cases to date. This study was supported by grants from the Ministerio de Educacion y Ciencia (MEC) [SAF2007-65542-C02-01, SAF2009_07072E; BES-2008-009234 to M.I.V. and CP08-0069 “Miquel Servet SNS Contract” to G.R.]; Ministerio de Ciencia e Innovacion [CGL2008-04066/BOS]; Network RD06-0020-1060; the Fundacion Mutua Madrileña and the Fundacion Hospital Provincial de Castellon, Spain. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Databáze: OpenAIRE
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