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dc.contributorMartí Laborda, Rosa Ma.
dc.contributor.authorSchoof, Nils
dc.contributor.authorIles, Mark M.
dc.contributor.authorBishop, D. Timothy
dc.contributor.authorNewton-Bishop, Julia A.
dc.contributor.authorBarrett, Jennifer H.
dc.contributor.authorGenoMEL consortium
dc.date.accessioned2015-06-09T09:34:26Z
dc.date.available2015-06-09T09:34:26Z
dc.date.issued2011
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/10459.1/48325
dc.description.abstractSystemic immunosuppression is a risk factor for melanoma, and sunburn-induced immunosuppression is thought to be causal. Genes in immunosuppression pathways are therefore candidate melanoma-susceptibility genes. If variants within these genes individually have a small effect on disease risk, the association may be undetected in genome-wide association (GWA) studies due to low power to reach a high significance level. Pathway-based approaches have been suggested as a method of incorporating a priori knowledge into the analysis of GWA studies. In this study, the association of 1113 single nucleotide polymorphisms (SNPs) in 43 genes (39 genomic regions) related to immunosuppression have been analysed using a gene-set approach in 1539 melanoma cases and 3917 controls from the GenoMEL consortium GWA study. The association between melanoma susceptibility and the whole set of tumour-immunosuppression genes, and also predefined functional subgroups of genes, was considered. The analysis was based on a measure formed by summing the evidence from the most significant SNP in each gene, and significance was evaluated empirically by case-control label permutation. An association was found between melanoma and the complete set of genes (pemp = 0.002), as well as the subgroups related to the generation of tolerogenic dendritic cells (pemp = 0.006) and secretion of suppressive factors (pemp = 0.0004), thus providing preliminary evidence of involvement of tumour-immunosuppression gene polymorphisms in melanoma susceptibility. The analysis was repeated on a second phase of the GenoMEL study, which showed no evidence of an association. As one of the first attempts to replicate a pathway-level association, our results suggest that low power and heterogeneity may present challenges.ca_ES
dc.language.isoengca_ES
dc.publisherPublic Library of Scienceca_ES
dc.relation.isformatofReproducció del document publicat a https://doi.org/10.1371/journal.pone.0029451ca_ES
dc.relation.ispartofPLoS One, 2011, vol. 6, núm. 12, e29451ca_ES
dc.rightscc-by, (c) Schoof et al., 2011ca_ES
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/es/*
dc.titlePathway-based analysis of a melanoma genome-wide association study: analysis of genes related to tumour-immunosuppressionca_ES
dc.typearticleca_ES
dc.identifier.idgrec018264
dc.type.versionpublishedVersionca_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccessca_ES
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0029451


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cc-by, (c) Schoof et al., 2011
Except where otherwise noted, this item's license is described as cc-by, (c) Schoof et al., 2011