title: Thyroid cancer GWAS identifies 10q26.12 and 6q14.1 as novel susceptibility loci and reveals genetic heterogeneity among populations.
abstract: Thyroid cancer is the most heritable cancer of all those not displaying typical Mendelian inheritance. However, most of the genetic factors that would explain the high heritability remain unknown. Our aim was to identify additional common genetic variants associated with susceptibility to this disease. In order to do so, we performed a genome-wide association study in a series of 398 cases and 502 controls from Spain, followed by a replication in four well-defined Southern European case-control collections contributing a total of 1,422 cases and 1,908 controls. The association between the variation at the 9q22 locus near FOXE1 and thyroid cancer risk was consistent across all series, with several SNPs identified (rs7028661: OR = 1.64, p = 1.0 × 10(-22) , rs7037324: OR = 1.54, p = 1.2 × 10(-17) ). Moreover, the rare alleles of three SNPs (rs2997312, rs10788123 and rs1254167) at 10q26.12 showed suggestive evidence of association with higher risk of the disease (OR = 1.35, p = 1.2 × 10(-04) , OR = 1.26, p = 5.2 × 10(-04) and OR = 1.38, p = 5.9 × 10(-05) , respectively). Finally, the rare allele of rs4075570 at 6q14.1 conferred protection in the series studied (OR = 0.82, p = 2.0 × 10(-04) ). This study suggests that heterogeneity in genetic susceptibility between populations is a key feature to take into account when exploring genetic risk factors related to this disease.
authors: CNIO, Hereditary Endocrine Cancer Group, Madrid, Spain.
authors: Veronika
authors: V
authors: Mancikova
authors: Genomic Medicine Group, IDIS, Galician Foundation of Genomic Medicine-SERGAS, Santiago De Compostela, Spain.|ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Madrid, Spain.
authors: Raquel
authors: R
authors: Cruz
authors: CNIO, Hereditary Endocrine Cancer Group, Madrid, Spain.|ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Madrid, Spain.
authors: Lucía
authors: L
authors: Inglada-Pérez
authors: Genomic Medicine Group, IDIS, Galician Foundation of Genomic Medicine-SERGAS, Santiago De Compostela, Spain.|Molecular and Population Genetics, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
authors: Ceres
authors: C
authors: Fernández-Rozadilla
authors: Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors: Iñigo
authors: I
authors: Landa
authors: Department of Anatomic Pathology, Clinical University Hospital (SERGAS), University of Santiago De Compostela, Spain.
authors: José
authors: J
authors: Cameselle-Teijeiro
authors: Genomic Medicine Group, IDIS, Galician Foundation of Genomic Medicine-SERGAS, Santiago De Compostela, Spain.|Department of Anatomic Pathology, Clinical University Hospital (SERGAS), University of Santiago De Compostela, Spain.
authors: Catuxa
authors: C
authors: Celeiro
authors: Departament De Genètica I De Microbiologia, Grup De Mutagènesi, Unitat De Genètica, Facultat De Biociències, Universitat Autònoma De Barcelona, Barcelona, Spain.|ISCIII, CIBER Epidemiologia Y Salud Pública, Madrid, Spain.
authors: Susana
authors: S
authors: Pastor
authors: Departament De Genètica I De Microbiologia, Grup De Mutagènesi, Unitat De Genètica, Facultat De Biociències, Universitat Autònoma De Barcelona, Barcelona, Spain.|ISCIII, CIBER Epidemiologia Y Salud Pública, Madrid, Spain.
authors: Antonia
authors: A
authors: Velázquez
authors: Departament De Genètica I De Microbiologia, Grup De Mutagènesi, Unitat De Genètica, Facultat De Biociències, Universitat Autònoma De Barcelona, Barcelona, Spain.|ISCIII, CIBER Epidemiologia Y Salud Pública, Madrid, Spain.
authors: Ricard
authors: R
authors: Marcos
authors: Hospital Gregorio Marañón, Madrid, Spain.
authors: Victor
authors: V
authors: Andía
authors: Hospital La Paz, Madrid, Spain.
authors: Cristina
authors: C
authors: Álvarez-Escolá
authors: Hospital Reina Sofía De Murcia, Murcia, Spain.
authors: Amparo
authors: A
authors: Meoro
authors: Veneto Institute of Oncology, IRCCS, Padova, Italy.
authors: Francesca
authors: F
authors: Schiavi
authors: Veneto Institute of Oncology, IRCCS, Padova, Italy.|Department of Medicine, DIMED, University of Padova, Italy.
authors: Giuseppe
authors: G
authors: Opocher
authors: Spanish National Genotyping Center-University of Santiago De Compostela, Prb2-Institute of Health Carlos III (ISCIII), Madrid, Spain.
authors: Inés
authors: I
authors: Quintela
authors: Spanish National Genotyping Center-University of Santiago De Compostela, Prb2-Institute of Health Carlos III (ISCIII), Madrid, Spain.
authors: Juan
authors: J
authors: Ansede-Bermejo
authors: Genomic Medicine Group, IDIS, Galician Foundation of Genomic Medicine-SERGAS, Santiago De Compostela, Spain.|ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Madrid, Spain.
authors: Clara
authors: C
authors: Ruiz-Ponte
authors: Instituto De Investigaciones Biomédicas "Alberto Sols,", Madrid, Spain.
authors: Pilar
authors: P
authors: Santisteban
authors: CNIO, Hereditary Endocrine Cancer Group, Madrid, Spain.|ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Madrid, Spain.
authors: Mercedes
authors: M
authors: Robledo
authors: Genomic Medicine Group, IDIS, Galician Foundation of Genomic Medicine-SERGAS, Santiago De Compostela, Spain.|ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Madrid, Spain.|Spanish National Genotyping Center-University of Santiago De Compostela, Prb2-Institute of Health Carlos III (ISCIII), Madrid, Spain.
authors: Angel
authors: A
authors: Carracedo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002648:Child; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D005260:Female; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D013030:Spain; D013964:Thyroid Neoplasms / Q000235:genetics*; D055815:Young Adult
keywords: FOXE1; HTR1B; genetic heterogeneity; susceptibility; thyroid cancer