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

  • Figlioli G 1] Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany [2] Department of Biology, University of Pisa, Pisa, Italy.
  • Chen B Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Elisei R Department of Endocrinology and Metabolism, University of Pisa, Pisa, Italy.
  • Romei C Department of Endocrinology and Metabolism, University of Pisa, Pisa, Italy.
  • Campo C 1] Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany [2] Department of Biology, University of Pisa, Pisa, Italy.
  • Cipollini M Department of Biology, University of Pisa, Pisa, Italy.
  • Cristaudo A Department of Endocrinology and Metabolism, University of Pisa, Pisa, Italy.
  • Bambi F Blood Centre, Azienda Ospedaliero Universitaria A. Meyer, Firenze, Italy.
  • Paolicchi E Department of Biology, University of Pisa, Pisa, Italy.
  • Hoffmann P 1] Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany [2] Institute of Human Genetics, University of Bonn, Bonn, Germany [3] Division of Medical Genetics, University Hospital Basel; Department of Biomedicine, University of Basel, Basel, Switzerland.
  • Herms S 1] Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany [2] Institute of Human Genetics, University of Bonn, Bonn, Germany [3] Division of Medical Genetics, University Hospital Basel; Department of Biomedicine, University of Basel, Basel, Switzerland.
  • Kalemba M Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland.
  • Kula D Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland.
  • Pastor S 1] Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Cerdanyola del Vallés, Barcelona, Spain [2] CIBER Epidemiologia y Salud Pública, ISCIII, Madrid, Spain.
  • Marcos R 1] Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Cerdanyola del Vallés, Barcelona, Spain [2] CIBER Epidemiologia y Salud Pública, ISCIII, Madrid, Spain.
  • Velázquez A 1] Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Cerdanyola del Vallés, Barcelona, Spain [2] CIBER Epidemiologia y Salud Pública, ISCIII, Madrid, Spain.
  • Jarząb B Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland.
  • Landi S Department of Biology, University of Pisa, Pisa, Italy.
  • Hemminki K 1] Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany [2] Center for Primary Health Care Research, Clinical Research Center, Lund University, Malmö, Sweden.
  • Gemignani F Department of Biology, University of Pisa, Pisa, Italy.
  • Försti A 1] Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany [2] Center for Primary Health Care Research, Clinical Research Center, Lund University, Malmö, Sweden.
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  • 2015-03-11
Published in:
  • Scientific reports. - 2015
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
English 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(-7)) and rs1203952 (FOXA2, OR = 1.29, 95%CI 1.16-1.44, p-value = 4.42 × 10(-6)). 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(-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.
Language
  • English
Open access status
gold
Identifiers
Persistent URL
https://sonar.ch/global/documents/53520
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