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The 8q24 rs6983267G variant is associated with increased thyroid cancer risk
Ruta Sahasrabudhe1, Ana Estrada1, Paul Lott1
1Department of Biochemistry and Molecular Medicine School of Medicine, UC Davis Genome Center, University of California, Davis, 451 Health Sciences Drive, Davis, California 95616, USA Grupo de Citogenética Filogenia y Evolución de Poblaciones, Facultad de Ciencias y Facultad de Ciencias de la Salud, Universidad del Tolima, Ibagué, Colombia Wellcome Trust Centre for Human Genetics University of Oxford, Oxford, UK Hospital Pablo Tobón Uribe Medellín, Colombia Division of Cancer Control and Population Sciences National Cancer Institute, Bethesda, Maryland, USA Center for the Promotion of Interdisciplinary Education and Research Graduate School of Medicine Center for Genomic Medicine, Kyoto University, Kyoto, Japan Departments of Molecular Epidemiology Radiation Medical Sciences Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan Nagasaki University Research Centre for Genomic Instability and Carcinogenesis Nagasaki, Japan Fundación de Genómica y Genética Molecular Ibagué, Colombia.
Abstract:
The G allele of the rs6983267 single-nucleotide polymorphism, located on chromosome 8q24, has been associated with increased risk of several cancer types. The association between rs6983267G and thyroid cancer (TC) has been tested in different populations, mostly of European ancestry, and has led to inconclusive results. While significant associations have been reported in the British and Polish populations, no association has been detected in populations from Spain, Italy and the USA. To further investigate the role of rs6983267G in TC susceptibility, we evaluated rs6983267 genotypes in three populations of different continental ancestry (British Isles, Colombia and Japan), providing a total of 3067 cases and 8575 controls. We detected significant associations between rs6983267G and TC in the British Isles (odds ratio (OR)=1.19, 95% CI: 1.11-1.27, P=4.03×10(-7)), Japan (OR=1.20, 95% CI: 1.03-1.41, P=0.022) and a borderline significant association of similar effect direction and size in Colombia (OR=1.19, 95% CI: 0.99-1.44, P=0.069). A meta-analysis of our multi-ethnic study and previously published non-overlapping datasets, which included a total of 5484 cases and 12 594 controls, confirmed the association between rs6983267G and TC (P=1.23×10(-7), OR=1.13, 95% CI: 1.08-1.18). Our results therefore support the notion that rs6983267G is a bona fide TC risk variant that increases the risk of disease by ∼13%.
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