Assessment of melanoma candidate genes in a meta-analysis of 16,534 melanoma cases.

Assessment of melanoma candidate genes in a meta-analysis of 16,534 melanoma cases.

Publication date: May 09, 2019

Numerous single nucleotide polymorphisms (SNPs) have been implicated with cutaneous melanoma (CM) Objective: The aim of our study was to establish novel susceptibility loci for CM by assessing candidate genes in a published meta-analysis of 11 genome-wide association studies (GWASs).

760 variants were retrieved from the MelGene database and tested for association in a meta-analysis of 11 GWASs consisting of 12,874 CM cases and 23,303 controls of European ancestry. We calculated a false discovery rate and variants that surpassed this p-value threshold were genotyped in three independent replication samples from UK, Greece and Cyprus. We excluded variants robustly associated with CM or in linkage disequilibrium with already known loci. The results from the GWASs and replication stages were synthesized in a meta-analysis.

Based on our approach, the rs909253 polymorphism in the LTA gene (Lymphotoxin Alpha) was followed up for further consideration. The meta-analysis of the 11 GWAS indicated a protective effect for the G allele on the risk of CM (OR: 0.921, p-value: 2.7×10-5). However, the estimates from the three replication samples were not statistically significant. The combined meta-analysis of 3,660 CM cases and 350,915 cancer-free controls provided a similar OR (0.935, p-value: 1.95×10-5); very large studies in the future will be required to determine if this SNP is a genuine melanoma risk SNP.

By assessing over 16,000 CM cases, none of the published candidate genes tested for association with CM were significant in our study. Interest should be shifted to larger GWAS. This article is protected by copyright. All rights reserved.

Ntritsos, G., Dimou, N., Kypreou, K., , Stefanaki, Loizidou, M.A., Hadjisavvas, A., Kyriacou, K., Consortium, Melanoma Meta-Analysis., MacGregor, S., Law, M.H., Iles, M.M., Stratigos, A.J., and Evangelou, E. Assessment of melanoma candidate genes in a meta-analysis of 16,534 melanoma cases. 22576. 2019 J Eur Acad Dermatol Venereol.

Concepts Keywords
Allele SNP
Cancer Meta-analysis
CM Alpha
Cyprus Melanoma
Genome RTT
Greece Single-nucleotide polymorphism
Linkage Disequilibrium Molecular biology
Loci Cancer
Melanoma Branches of biology
Meta Analysis Life sciences
Polymorphism Population genetics
Single Nucleotide Polymorphisms Assessment melanoma
SNP SNP genuine melanoma
SNPs Melanoma
Cancer

Semantics

Type Source Name
disease DOID melanoma
pathway BSID Melanoma
disease MESH melanoma
disease DOID cancer
gene UNIPROT LARGE1
disease MESH cancer
gene UNIPROT LTA
disease DOID cutaneous melanoma
gene UNIPROT CD5L
gene UNIPROT CD69
gene UNIPROT DNMT1

Original Article

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