Thyroid cancer GWAS identifies 10q26.12 and 6q14.1 as novel susceptibility loci and reveals genetic heterogeneity among populations |
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| Authors: | Lucía Inglada‐Pérez Ceres Fernández‐Rozadilla Iñigo Landa José Cameselle‐Teijeiro Catuxa Celeiro Susana Pastor Antonia Velázquez Ricard Marcos Victor Andía Cristina Álvarez‐Escolá Amparo Meoro Francesca Schiavi Giuseppe Opocher Inés Quintela Juan Ansede‐Bermejo Clara Ruiz‐Ponte Pilar Santisteban Mercedes Robledo Angel Carracedo |
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| Affiliation: | 1. CNIO, Hereditary Endocrine Cancer Group, Madrid, Spain;2. ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Madrid, Spain;3. Genomic Medicine Group, IDIS, Galician Foundation of Genomic Medicine‐SERGAS, Santiago De Compostela, Spain;4. Molecular and Population Genetics, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom;5. Human Oncology and Pathogenesis Program, Memorial Sloan‐Kettering Cancer Center, New York, New York;6. Department of Anatomic Pathology, Clinical University Hospital (SERGAS), University of Santiago De Compostela, Spain;7. Departament De Genètica I De Microbiologia, Grup De Mutagènesi, Unitat De Genètica, Facultat De Biociències, Universitat Autònoma De Barcelona, Barcelona, Spain;8. ISCIII, CIBER Epidemiologia Y Salud Pública, Madrid, Spain;9. Hospital Gregorio Mara?ón, Madrid, Spain;10. Hospital La Paz, Madrid, Spain;11. Hospital Reina Sofía De Murcia, Murcia, Spain;12. Veneto Institute of Oncology, IRCCS, Padova, Italy;13. Department of Medicine, DIMED, University of Padova, Italy;14. Spanish National Genotyping Center‐University of Santiago De Compostela, Prb2—Institute of Health Carlos III (ISCIII), Madrid, Spain;15. Instituto De Investigaciones Biomédicas “Alberto Sols,”, Madrid, Spain |
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| 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. |
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| Keywords: | thyroid cancer susceptibility genetic heterogeneity FOXE1 HTR1B |
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