Novel genetic variants in differentiated thyroid cancer and assessment of the cumulative risk

A genome-wide association study (GWAS) performed on a high-incidence Italian population followed by replications on low-incidence cohorts suggested a strong association of differentiated thyroid cancer (DTC) with single nucleotide polymorphisms (SNPs) at 9q22.33, 2q35, 20q11.22-q12 and 14q24.3. More...

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Detalles Bibliográficos
Autores: Figlioli, Gisella|||0000-0002-0740-1363, Chen, Bowang, Elisei, Rossella|||0000-0002-5333-9257, Romei, Cristina|||0000-0002-2773-1968, Campo, Chiara, Cipollini, Monica|||0000-0002-0117-3152, Cristaudo, Alfonso|||0000-0001-6575-5701, Bambi, Franco|||0000-0002-1945-8324, Paolicchi, Elisa|||0000-0001-6101-7576, Hoffmann, Per|||0000-0002-6573-983X, Herms, Stefan|||0000-0002-2786-8200, Kalemba, Michał|||0000-0002-3887-5465, Kula, Dorota|||0000-0002-0986-1929, Pastor Benito, Susana|||0000-0003-2454-5163, Marcos Dauder, Ricardo|||0000-0001-7891-357X, Velázquez Henar, Antonia|||0000-0003-3254-4312, Jarząb, Barbara|||0000-0001-9811-9584, Landi, Stefano|||0000-0001-8364-6357, Hemminki, Kari|||0000-0002-2769-3316, Gemignani, Federica|||0000-0003-1297-0701, Försti, Asta|||0000-0002-9857-4728
Tipo de recurso: artículo
Fecha de publicación:2015
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:203838
Acceso en línea:https://ddd.uab.cat/record/203838
https://dx.doi.org/urn:doi:10.1038/srep08922
Access Level:acceso abierto
Palabra clave:Alleles
Genetic Predisposition to Disease
Genetics Population
Genome-Wide Association Study
Genotype
Hepatocyte Nuclear Factor 3-beta
Humans
Italy
N-Acetylgalactosaminyltransferases
Polymorphism Single Nucleotide
Risk Factors
Thyroid Neoplasms
Descripción
Sumario:A genome-wide association study (GWAS) performed on a high-incidence Italian population followed by replications on low-incidence cohorts suggested a strong association of differentiated thyroid cancer (DTC) with single nucleotide polymorphisms (SNPs) at 9q22.33, 2q35, 20q11.22-q12 and 14q24.3. Moreover, six additional susceptibility loci were associated with the disease only among Italians. The present study had two aims, first to identify loci involved in DTC risk and then to assess the cumulative effect of the SNPs identified so far in the Italian population. The combined analysis of the previous GWAS and the present Italian study provided evidence of association with rs7935113 (GALNTL4, OR = 1.36, 95%CI 1.20-1.53, p-value = 7.41 × 10) and rs1203952 (FOXA2, OR = 1.29, 95%CI 1.16-1.44, p-value = 4.42 × 10). Experimental ENCODE and eQTL data suggested that both SNPs may influence the closest genes expression through a differential recruitment of transcription factors. The assessment of the cumulative risk of eleven SNPs showed that DTC risk increases with an increasing number of risk alleles (p-trend = 3.13 × 10 â '47). Nonetheless, only a small fraction (about 4% on the disease liability scale) of DTC is explained by these SNPs. These data are consistent with a polygenic model of DTC predisposition and highlight the importance of association studies in the discovery of the disease hereditability.

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