TY - JOUR
T1 - Thyroid cancer GWAS identifies 10q26.12 and 6q14.1 as novel susceptibility loci and reveals genetic heterogeneity among populations
AU - Mancikova, Veronika
AU - Cruz, Raquel
AU - Inglada-Pérez, Lucía
AU - Fernández-Rozadilla, Ceres
AU - Landa, Iñigo
AU - Cameselle-Teijeiro, José
AU - Celeiro, Catuxa
AU - Pastor, Susana
AU - Velázquez, Antonia
AU - Marcos, Ricard
AU - Andía, Victor
AU - Álvarez-Escolá, Cristina
AU - Meoro, Amparo
AU - Schiavi, Francesca
AU - Opocher, Giuseppe
AU - Quintela, Inés
AU - Ansede-Bermejo, Juan
AU - Ruiz-Ponte, Clara
AU - Santisteban, Pilar
AU - Robledo, Mercedes
AU - Carracedo, Angel
PY - 2015/10/15
Y1 - 2015/10/15
N2 - © 2015 UICC. 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. What's new? Thyroid cancer shows the highest genetic susceptibility among all cancers with non-Mendelian hereditability. The authors performed a two-step association study involving 1820 cases and 2410 controls in Europe and identify the 9q22 locus near the FOXE1 locus as the most important low-penetrance variation in thyroid cancer. In addition, novel variations at 10q26.12 and 6q14.1 were found associated with risk of the disease in a population-specific manner, underscoring how genetic heterogeneity among populations influences thyroid cancer susceptibility.
AB - © 2015 UICC. 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. What's new? Thyroid cancer shows the highest genetic susceptibility among all cancers with non-Mendelian hereditability. The authors performed a two-step association study involving 1820 cases and 2410 controls in Europe and identify the 9q22 locus near the FOXE1 locus as the most important low-penetrance variation in thyroid cancer. In addition, novel variations at 10q26.12 and 6q14.1 were found associated with risk of the disease in a population-specific manner, underscoring how genetic heterogeneity among populations influences thyroid cancer susceptibility.
KW - FOXE1
KW - HTR1B
KW - genetic heterogeneity
KW - susceptibility
KW - thyroid cancer
U2 - 10.1002/ijc.29557
DO - 10.1002/ijc.29557
M3 - Article
SN - 0020-7136
VL - 137
SP - 1870
EP - 1878
JO - International Journal of Cancer
JF - International Journal of Cancer
ER -
