TY - JOUR
T1 - Genome-wide association study on differentiated thyroid cancer
AU - Köhler, Aleksandra
AU - Chen, Bowang
AU - Gemignani, Federica
AU - Elisei, Rossella
AU - Romei, Cristina
AU - Figlioli, Gisella
AU - Cipollini, Monica
AU - Cristaudo, Alfonso
AU - Bambi, Franco
AU - Hoffmann, Per
AU - Herms, Stefan
AU - Kalemba, Michał
AU - Kula, Dorota
AU - Harris, Shelley
AU - Broderick, Peter
AU - Houlston, Richard
AU - Pastor, Susana
AU - Marcos, Ricard
AU - Velázquez, Antonia
AU - Jarzab, Barbara
AU - Hemminki, Kari
AU - Landi, Stefano
AU - Försti, Asta
PY - 2013/10/1
Y1 - 2013/10/1
N2 - Context: Genome-wide association studies (GWASs) of differentiated thyroid cancer (DTC) have identified associations with polymorphisms at 2q35 (DIRC3), 8p12 (NRG1), 9q22.33 (FOXE1), and 14q13.2 (NKX2-1). However, most of the inherited genetic risk factors of DTC remain to be discovered. Objective: Our objective was to identify additional common DTC susceptibility loci. Design: We conducted a GWAS in a high-incidence Italian population of 690 cases and 497 controls and followed up the most significant polymorphisms in 2 additional Italian series and in 3 low-incidence populations totaling 2958 cases and 3727 controls. Results: After excluding the most robust previously identified locus (9q22.33), the strongest association was shown by rs6759952, confirming the recently published association in DIRC3 (odds ratio [OR] = 1.21, P = 6.4 × 10-10, GWAS and all replications combined). Additionally, in the combined analysis of the Italian series, suggestive associations were attained with rs10238549 and rs7800391 in IMMP2L (OR = 1.27, P = 4.1 × 10 -6; and OR= 1.25, P= 5.7 × 10-6), rs7617304 in RARRES1 (OR = 1.25, P = 4.6 × 10-5) and rs10781500 in SNAPC4/CARD9 (OR = 1.23, P = 3.5 × 10-5). Conclusions: Our findings provide additional insights into the genetic and biological basis of inherited genetic susceptibility to DTC. Additional studies are needed to determine the role of the identified polymorphisms in the development of DTC and their possible use in the clinical practice. Copyright © 2013 by The Endocrine Society.
AB - Context: Genome-wide association studies (GWASs) of differentiated thyroid cancer (DTC) have identified associations with polymorphisms at 2q35 (DIRC3), 8p12 (NRG1), 9q22.33 (FOXE1), and 14q13.2 (NKX2-1). However, most of the inherited genetic risk factors of DTC remain to be discovered. Objective: Our objective was to identify additional common DTC susceptibility loci. Design: We conducted a GWAS in a high-incidence Italian population of 690 cases and 497 controls and followed up the most significant polymorphisms in 2 additional Italian series and in 3 low-incidence populations totaling 2958 cases and 3727 controls. Results: After excluding the most robust previously identified locus (9q22.33), the strongest association was shown by rs6759952, confirming the recently published association in DIRC3 (odds ratio [OR] = 1.21, P = 6.4 × 10-10, GWAS and all replications combined). Additionally, in the combined analysis of the Italian series, suggestive associations were attained with rs10238549 and rs7800391 in IMMP2L (OR = 1.27, P = 4.1 × 10 -6; and OR= 1.25, P= 5.7 × 10-6), rs7617304 in RARRES1 (OR = 1.25, P = 4.6 × 10-5) and rs10781500 in SNAPC4/CARD9 (OR = 1.23, P = 3.5 × 10-5). Conclusions: Our findings provide additional insights into the genetic and biological basis of inherited genetic susceptibility to DTC. Additional studies are needed to determine the role of the identified polymorphisms in the development of DTC and their possible use in the clinical practice. Copyright © 2013 by The Endocrine Society.
U2 - 10.1210/jc.2013-1941
DO - 10.1210/jc.2013-1941
M3 - Article
SN - 0021-972X
VL - 98
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
ER -
