Novel genetic variants in differentiated thyroid cancer and assessment of the cumulative risk
Figlioli, Gisella (University of Pisa. Department of Biology)
Chen, Bowang (German Cancer Research Center (DKFZ). Molecular Genetic Epidemiology (Germany))
Elisei, Rossella (University of Pisa. Department of Endocrinology and Metabolism (Italy))
Romei, Cristina (University of Pisa. Department of Endocrinology and Metabolism (Italy))
Campo, Chiara (University of Pisa. Department of Biology (Italy))
Cipollini, Monica (University of Pisa. Department of Biology (Italy))
Cristaudo, Alfonso (University of Pisa. Department of Endocrinology and Metabolism (Italy))
Bambi, Franco (Blood Centre, Azienda Ospedaliero Universitaria A. Meyer (Italy))
Paolicchi, Elisa (University of Pisa. Department of Biology (Italy))
Hoffmann, Per (University of Basel (Suïssa). Department of Biomedicine)
Herms, Stefan (University of Basel (Suïssa). Department of Biomedicine)
Kalemba, Michał (Maria Sklodowska-Curie Memorial Cancer Center. Department of Nuclear Medicine and Endocrine Oncology (Poland))
Kula, Dorota (Maria Sklodowska-Curie Memorial Cancer Center. Department of Nuclear Medicine and Endocrine Oncology (Poland))
Pastor Benito, Susana (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Marcos Dauder, Ricardo (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Velázquez Henar, Antonia (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Jarząb, Barbara (Maria Sklodowska-Curie Memorial Cancer Center. Department of Nuclear Medicine and Endocrine Oncology (Poland))
Landi, Stefano (University of Pisa. Department of Biology (Italy))
Hemminki, Kari (Lund University. Center for Primary Health Care Research, Clinical Research Center (Sweden))
Gemignani, Federica (University of Pisa. Department of Biology (Italy))
Försti, Asta (Lund University. Center for Primary Health Care Research, Clinical Research Center (Sweden))

Date:	2015
Abstract:	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.
Grants:	Agència de Gestió d'Ajuts Universitaris i de Recerca 2009/SGR-725
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	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
Published in:	Scientific reports, Vol. 5 (March 2015) , art. 8922, ISSN 2045-2322

DOI: 10.1038/srep08922
PMID: 25753578

7 p, 508.5 KB

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