title: A genome-wide association study yields five novel thyroid cancer risk loci.
abstract: The great majority of thyroid cancers are of the non-medullary type. Here we report findings from a genome-wide association study of non-medullary thyroid cancer, including in total 3,001 patients and 287,550 controls from five study groups of European descent. Our results yield five novel loci (all with Pcombined<3 × 10-8): 1q42.2 (rs12129938 in PCNXL2), 3q26.2 (rs6793295 a missense mutation in LRCC34 near TERC), 5q22.1 (rs73227498 between NREP and EPB41L4A), 10q24.33 (rs7902587 near OBFC1), and two independently associated variants at 15q22.33 (rs2289261 and rs56062135; both in SMAD3). We also confirm recently published association results from a Chinese study of a variant on 5p15.33 (rs2736100 near the TERT gene) and present a stronger association result for a moderately correlated variant (rs10069690; OR=1.20, P=3.2 × 10-7) based on our study of individuals of European ancestry. In combination, these results raise several opportunities for future studies of the pathogenesis of thyroid cancer.
authors.affiliation: deCODE genetics/AMGEN, 101 Reykjavik, Iceland.
authors.forename: Julius
authors.initials: J
authors.lastname: Gudmundsson
authors.affiliation: deCODE genetics/AMGEN, 101 Reykjavik, Iceland.
authors.forename: Gudmar
authors.initials: G
authors.lastname: Thorleifsson
authors.affiliation: deCODE genetics/AMGEN, 101 Reykjavik, Iceland.
authors.forename: Jon K
authors.initials: JK
authors.lastname: Sigurdsson
authors.affiliation: deCODE genetics/AMGEN, 101 Reykjavik, Iceland.
authors.forename: Lilja
authors.initials: L
authors.lastname: Stefansdottir
authors.affiliation: Landspitali-University Hospital, 101 Reykjavik, Iceland.|Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland.|The Icelandic Cancer Registry, 105 Reykjavik, Iceland.
authors.forename: Jon G
authors.initials: JG
authors.lastname: Jonasson
authors.affiliation: deCODE genetics/AMGEN, 101 Reykjavik, Iceland.
authors.forename: Sigurjon A
authors.initials: SA
authors.lastname: Gudjonsson
authors.affiliation: deCODE genetics/AMGEN, 101 Reykjavik, Iceland.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Gudbjartsson
authors.affiliation: deCODE genetics/AMGEN, 101 Reykjavik, Iceland.
authors.forename: Gisli
authors.initials: G
authors.lastname: Masson
authors.affiliation: deCODE genetics/AMGEN, 101 Reykjavik, Iceland.
authors.forename: Hrefna
authors.initials: H
authors.lastname: Johannsdottir
authors.affiliation: deCODE genetics/AMGEN, 101 Reykjavik, Iceland.
authors.forename: Gisli H
authors.initials: GH
authors.lastname: Halldorsson
authors.affiliation: deCODE genetics/AMGEN, 101 Reykjavik, Iceland.
authors.forename: Simon N
authors.initials: SN
authors.lastname: Stacey
authors.affiliation: deCODE genetics/AMGEN, 101 Reykjavik, Iceland.|School of Engineering and Natural Sciences, University of Iceland, 101 Reykjavik, Iceland.
authors.forename: Hannes
authors.initials: H
authors.lastname: Helgason
authors.affiliation: deCODE genetics/AMGEN, 101 Reykjavik, Iceland.
authors.forename: Patrick
authors.identifier: 0000-0001-7123-6123
authors.initials: P
authors.lastname: Sulem
authors.affiliation: Division of Human Genetics, Ohio State University Comprehensive Cancer Center, Columbus, Ohio 43210, USA.
authors.forename: Leigha
authors.initials: L
authors.lastname: Senter
authors.affiliation: Department of Cancer Biology and Genetics, Ohio State University Comprehensive Cancer Center, Columbus, Ohio 43210, USA.
authors.forename: Huiling
authors.initials: H
authors.lastname: He
authors.affiliation: Department of Cancer Biology and Genetics, Ohio State University Comprehensive Cancer Center, Columbus, Ohio 43210, USA.
authors.forename: Sandya
authors.initials: S
authors.lastname: Liyanarachchi
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Ringel
authors.affiliation: Division of Endocrinology, University Hospital, 50009 Zaragoza, Spain.
authors.forename: Esperanza
authors.initials: E
authors.lastname: Aguillo
authors.affiliation: Division of Medical Oncology, Ciudad de Coria Hospital, 10800 Coria, Spain.
authors.forename: Angeles
authors.initials: A
authors.lastname: Panadero
authors.affiliation: Division of Nuclear Medicine, University Hospital, 50009 Zaragoza, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Prats
authors.affiliation: Division of Medical Oncology, Marques de Valdecilla University Hospital, 39008 Santander, Spain.
authors.forename: Almudena
authors.initials: A
authors.lastname: Garcia-Castaño
authors.affiliation: Division of Medical Oncology, Marques de Valdecilla University Hospital, 39008 Santander, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: De Juan
authors.affiliation: Division of Medical Oncology, Marques de Valdecilla University Hospital, 39008 Santander, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Rivera
authors.affiliation: Department of Head &Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Xu
authors.affiliation: Radboud University Medical Centre, Radboud Institute for Health Sciences, 6500HB Nijmegen, The Netherlands.
authors.forename: Lambertus A
authors.initials: LA
authors.lastname: Kiemeney
authors.affiliation: The Laboratory in Mjodd, 109 Reykjavik, Iceland.
authors.forename: Gudmundur I
authors.initials: GI
authors.lastname: Eyjolfsson
authors.affiliation: Department of Clinical Biochemistry, Akureyri Hospital, 600 Akureyri, Iceland.
authors.forename: Olof
authors.initials: O
authors.lastname: Sigurdardottir
authors.affiliation: Landspitali-University Hospital, 101 Reykjavik, Iceland.
authors.forename: Isleifur
authors.initials: I
authors.lastname: Olafsson
authors.affiliation: Landspitali-University Hospital, 101 Reykjavik, Iceland.
authors.forename: Hoskuldur
authors.initials: H
authors.lastname: Kristvinsson
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, Radboud University Medical Centre, Radboud Institute for Health Sciences, 6500HB Nijmegen, The Netherlands.
authors.forename: Romana T
authors.initials: RT
authors.lastname: Netea-Maier
authors.affiliation: Landspitali-University Hospital, 101 Reykjavik, Iceland.|Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland.
authors.forename: Thorvaldur
authors.initials: T
authors.lastname: Jonsson
authors.affiliation: University of Colorado Hospital, Aurora, Colorado 80045, USA.
authors.forename: Jose I
authors.initials: JI
authors.lastname: Mayordomo
authors.affiliation: Department of Pathology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, 6500HB Nijmegen, The Netherlands.
authors.forename: Theo S
authors.initials: TS
authors.lastname: Plantinga
authors.affiliation: Landspitali-University Hospital, 101 Reykjavik, Iceland.
authors.forename: Hannes
authors.initials: H
authors.lastname: Hjartarson
authors.affiliation: Landspitali-University Hospital, 101 Reykjavik, Iceland.
authors.forename: Jon
authors.initials: J
authors.lastname: Hrafnkelsson
authors.affiliation: Department of Head &Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Erich M
authors.initials: EM
authors.lastname: Sturgis
authors.affiliation: deCODE genetics/AMGEN, 101 Reykjavik, Iceland.|Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland.
authors.forename: Unnur
authors.initials: U
authors.lastname: Thorsteinsdottir
authors.affiliation: deCODE genetics/AMGEN, 101 Reykjavik, Iceland.
authors.forename: Thorunn
authors.initials: T
authors.lastname: Rafnar
authors.affiliation: Department of Cancer Biology and Genetics, Ohio State University Comprehensive Cancer Center, Columbus, Ohio 43210, USA.
authors.forename: Albert
authors.identifier: 0000-0001-9345-9248
authors.initials: A
authors.lastname: de la Chapelle
authors.affiliation: deCODE genetics/AMGEN, 101 Reykjavik, Iceland.|Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland.
authors.forename: Kari
authors.initials: K
authors.lastname: Stefansson
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D002291:Carcinoma, Papillary / Q000235:genetics*; D016022:Case-Control Studies; D002877:Chromosomes, Human / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency / Q000235:genetics; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D056914:Genomic Structural Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010907:Pituitary Hormones / Q000032:analysis; D012307:Risk Factors; D000077273:Thyroid Cancer, Papillary; D013961:Thyroid Gland / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism; D044465:White People / Q000235:genetics; D000073336:Whole Genome Sequencing
chemical_list: D010907:Pituitary Hormones