Thyroid cancer GWAS identifies 10q26.12 and 6q14.1 as novel susceptibility loci and reveals genetic heterogeneity among populations

摘要: Thyroid cancer is the most heritable of all those not displaying typical Mendelian inheritance. However, genetic factors that would explain high heritability remain unknown. Our aim was to identify additional common variants associated with susceptibility this disease. In order do so, we performed a genome-wide association study in series 398 cases and 502 controls from Spain, followed by replication four well-defined Southern European case-control collections contributing total 1,422 1,908 controls. The between variation at 9q22 locus near FOXE1 thyroid risk consistent across series, several SNPs identified (rs7028661: OR-‰=-‰1.64, p-‰=-‰1.0 × 10-22, rs7037324: OR-‰=-‰1.54, p-‰=-‰1.2 10-17). Moreover, rare alleles three (rs2997312, rs10788123 rs1254167) 10q26.12 showed suggestive evidence higher disease (OR-‰=-‰1.35, 10-04, OR-‰=-‰1.26, p-‰=-‰5.2 10-04 OR-‰=-‰1.38, p-‰=-‰5.9 10-05, respectively). Finally, allele rs4075570 6q14.1 conferred protection studied (OR-‰=-‰0.82, p-‰=-‰2.0 10-04). This suggests heterogeneity populations key feature take into account when exploring related What's new? shows highest among cancers non-Mendelian hereditability. authors two-step involving 1820 2410 Europe as important low-penetrance cancer. addition, novel variations were found population-specific manner, underscoring how influences susceptibility.