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.
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.
Authors: Julius Gudmundsson; Gudmar Thorleifsson; Jon K Sigurdsson; Lilja Stefansdottir; Jon G Jonasson; Sigurjon A Gudjonsson; Daniel F Gudbjartsson; Gisli Masson; Hrefna Johannsdottir; Gisli H Halldorsson; Simon N Stacey; Hannes Helgason; Patrick Sulem; Leigha Senter; Huiling He; Sandya Liyanarachchi; Matthew D Ringel; Esperanza Aguillo; Angeles Panadero; Enrique Prats; Almudena Garcia-Castaño; Ana De Juan; Fernando Rivera; Li Xu; Lambertus A Kiemeney; Gudmundur I Eyjolfsson; Olof Sigurdardottir; Isleifur Olafsson; Hoskuldur Kristvinsson; Romana T Netea-Maier; Thorvaldur Jonsson; Jose I Mayordomo; Theo S Plantinga; Hannes Hjartarson; Jon Hrafnkelsson; Erich M Sturgis; Unnur Thorsteinsdottir; Thorunn Rafnar; Albert de la Chapelle; Kari Stefansson Journal: Nat Commun Date: 2017-02-14 Impact factor: 14.919
Authors: Sandya Liyanarachchi; Julius Gudmundsson; Egil Ferkingstad; Huiling He; Jon G Jonasson; Vinicius Tragante; Folkert W Asselbergs; Li Xu; Lambertus A Kiemeney; Romana T Netea-Maier; Jose I Mayordomo; Theo S Plantinga; Hannes Hjartarson; Jon Hrafnkelsson; Erich M Sturgis; Pamela Brock; Fadi Nabhan; Gudmar Thorleifsson; Matthew D Ringel; Kari Stefansson; Albert de la Chapelle Journal: Proc Natl Acad Sci U S A Date: 2020-03-04 Impact factor: 11.205
Authors: Huiling He; Wei Li; Sandya Liyanarachchi; Mukund Srinivas; Yanqiang Wang; Keiko Akagi; Yao Wang; Dayong Wu; Qianben Wang; Victor Jin; David E Symer; Rulong Shen; John Phay; Rebecca Nagy; Albert de la Chapelle Journal: Proc Natl Acad Sci U S A Date: 2015-04-27 Impact factor: 11.205