Common variants on 9q22.33 and 14q13.3 predispose to thyroid cancer in European populations

被引：308

作者：

Gudmundsson, Julius ^{[1
]}

Sulem, Patrick ^{[1
]}

Gudbjartsson, Daniel F. ^{[1
]}

Jonasson, Jon G. ^{[2
,3
,4
]}

Sigurdsson, Asgeir ^{[1
]}

Bergthorsson, Jon T. ^{[1
,5
]}

He, Huiling

Blondal, Thorarinn ^{[1
]}

Geller, Frank ^{[1
]}

Jakobsdottir, Margret ^{[1
]}

Magnusdottir, Droplaug N. ^{[1
]}

Matthiasdottir, Sigurborg ^{[1
]}

Stacey, Simon N. ^{[1
]}

Skarphedinsson, Oskar B. ^{[1
]}

Helgadottir, Hafdis ^{[1
]}

Li, Wei ^{[5
]}

Nagy, Rebecca ^{[5
]}

Aguillo, Esperanza ^{[6
]}

Faure, Eduardo ^{[6
]}

Prats, Enrique ^{[7
]}

Saez, Berta ^{[8
]}

Martinez, Mariano ^{[9
]}

Eyjolfsson, Gudmundur I. ^{[10
]}

Bjornsdottir, Unnur S. ^{[3
]}

Holm, Hilma ^{[1
,11
]}

Kristjansson, Kristleifur ^{[1
]}

Frigge, Michael L. ^{[1
]}

Kristvinsson, Hoskuldur ^{[12
]}

Gulcher, Jeffrey R. ^{[1
]}

Jonsson, Thorvaldur ^{[3
,12
]}

Rafnar, Thorunn ^{[1
]}

Hjartarsson, Hannes ^{[13
]}

Mayordomo, Jose I. ^{[8
,14
]}

de la Chapelle, Albert ^{[5
]}

Hrafnkelsson, Jon ^{[15
]}

Thorsteinsdottir, Unnur ^{[1
,3
]}

Kong, Augustine ^{[1
]}

Stefansson, Kari ^{[1
,3
]}

机构：

[1] deCODE Genet, IS-101 Reykjavik, Iceland

[2] Landspitali Univ Hosp Hringbraut, Dept Pathol, IS-101 Reykjavik, Iceland

[3] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland

[4] Iceland Canc Registry, IS-105 Reykjavik, Iceland

[5] Ohio State Univ, Ctr Comprehens Canc, Human Canc Genet Program, Columbus, OH 43210 USA

[6] Univ Hosp, Div Endocrinol, Zaragoza 50009, Spain

[7] Univ Hosp, Div Nucl Med, Zaragoza 50009, Spain

[8] Nanotechnol Inst Aragon, Hlth Sci Inst, Zaragoza 50009, Spain

[9] Univ Hosp, Div Surg, Zaragoza 50009, Spain

[10] Lab Mjodd, IS-109 Reykjavik, Iceland

[11] Emory Univ, Sch Med, Dept Internal Med, Div Cardiol, Atlanta, GA 30322 USA

[12] Landspitali Univ Hosp Hringbraut, Dept Surg, IS-101 Reykjavik, Iceland

[13] Landspitali Univ Hosp Fossvogi, H&N Surg Dept, ORL, IS-108 Reykjavik, Iceland

[14] Univ Zaragoza, Lozano Blesa Univ Hosp, Div Med Oncol, E-50009 Zaragoza, Spain

[15] Landspitali Univ Hosp Hringbraut, Dept Oncol, IS-101 Reykjavik, Iceland

来源：

NATURE GENETICS | 2009年 / 41卷 / 04期

基金：

美国国家卫生研究院;

关键词：

SEQUENCE VARIANTS; CLEFT-PALATE; CARCINOMA; RISK; SUSCEPTIBILITY; ASSOCIATION; EXPRESSION; NEOPLASIA; GENETICS; ICELAND;

D O I：

10.1038/ng.339

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

In order to search for sequence variants conferring risk of thyroid cancer we conducted a genome-wide association study in 192 and 37,196 Icelandic cases and controls, respectively, followed by a replication study in individuals of European descent. Here we show that two common variants, located on 9q22.33 and 14q13.3, are associated with the disease. Overall, the strongest association signals were observed for rs965513 on 9q22.33 ( OR = 1.75; P = 1.7 x 10(-27)) and rs944289 on 14q13.3 (OR = 1.37; P = 2.0 x 10(-9)). The gene nearest to the 9q22.33 locus is FOXE1 (TTF2) and NKX2-1 (TTF1) is among the genes located at the 14q13.3 locus. Both variants contribute to an increased risk of both papillary and follicular thyroid cancer. Approximately 3.7% of individuals are homozygous for both variants, and their estimated risk of thyroid cancer is 5.7-fold greater than that of noncarriers. In a study on a large sample set from the general population, both risk alleles are associated with low concentrations of thyroid stimulating hormone (TSH), and the 9q22.33 allele is associated with low concentration of thyroxin (T-4) and high concentration of triiodothyronine (T-3).

引用

页码：460 / 464

页数：5

共 35 条

[1] Common variants on 9q22.33 and 14q13.3 predispose to thyroid cancer in European populations
Julius Gudmundsson
Patrick Sulem
Daniel F Gudbjartsson
Jon G Jonasson
Asgeir Sigurdsson
Jon T Bergthorsson
Huiling He
Thorarinn Blondal
Frank Geller
Margret Jakobsdottir
Droplaug N Magnusdottir
Sigurborg Matthiasdottir
Simon N Stacey
Oskar B Skarphedinsson
Hafdis Helgadottir
Wei Li
Rebecca Nagy
Esperanza Aguillo
Eduardo Faure
Enrique Prats
Berta Saez
Mariano Martinez
Gudmundur I Eyjolfsson
Unnur S Bjornsdottir
Hilma Holm
Kristleifur Kristjansson
Michael L Frigge
Hoskuldur Kristvinsson
Jeffrey R Gulcher
Thorvaldur Jonsson
Thorunn Rafnar
Hannes Hjartarsson
Jose I Mayordomo
Albert de la Chapelle
Jon Hrafnkelsson
Unnur Thorsteinsdottir
Augustine Kong
Kari Stefansson
Nature Genetics, 2009, 41 : 460 - 464
[2] Common variants at the 9q22.33, 14q13.3 and ATM loci, and risk of differentiated thyroid cancer in the Cuban population
Celia M Pereda
Fabienne Lesueur
Maroulio Pertesi
Nivonirina Robinot
Juan J Lence-Anta
Silvia Turcios
Milagros Velasco
Mae Chappe
Idalmis Infante
Marlene Bustillo
Anabel García
Enora Clero
Constance Xhaard
Yan Ren
Stéphane Maillard
Francesca Damiola
Carole Rubino
Sirced Salazar
Regla Rodriguez
Rosa M Ortiz
Florent de Vathaire
BMC Genetics, 16
[3] Common variants at the 9q22.33, 14q13.3 and ATM loci, and risk of differentiated thyroid cancer in the Cuban population
Pereda, Celia M.
Lesueur, Fabienne
Pertesi, Maroulio
Robinot, Nivonirina
Lence-Anta, Juan J.
Turcios, Silvia
Velasco, Milagros
Chappe, Mae
Infante, Idalmis
Bustillo, Marlene
Garcia, Anabel
Clero, Enora
Xhaard, Constance
Ren, Yan
Maillard, Stephane
Damiola, Francesca
Rubino, Carole
Salazar, Sirced
Rodriguez, Regla
Ortiz, Rosa M.
de Vathaire, Florent
BMC GENETICS, 2015, 16
[4] Common Variants at 9q22.33, 14q13.3, and ATM Loci, and Risk of Differentiated Thyroid Cancer in the French Polynesian Population
Maillard, Stephane
Damiola, Francesca
Clero, Enora
Pertesi, Maroulio
Robinot, Nivonirina
Rachedi, Frederique
Boissin, Jean-Louis
Sebbag, Joseph
Shan, Larrys
Bost-Bezeaud, Frederique
Petitdidier, Patrick
Doyon, Francoise
Xhaard, Constance
Rubino, Carole
Blanche, Helene
Drozdovitch, Vladimir
Lesueur, Fabienne
de Vathaire, Florent
PLOS ONE, 2015, 10 (04):
[5] Common genetic variants in 11q13.3 and 9q22.33 are associated with molecular subgroups of multiple myeloma
Erickson, S. W.
Stephens, O. W.
Chavan, S. S.
Tian, E.
Epstein, J.
Barlogie, B.
Heuck, C. J.
Vangsted, A. J.
LEUKEMIA, 2015, 29 (12) : 2418 - 2421
[6] Common genetic variants in 11q13.3 and 9q22.33 are associated with molecular subgroups of multiple myeloma
S W Erickson
O W Stephens
S S Chavan
E Tian
J Epstein
B Barlogie
C J Heuck
A J Vangsted
Leukemia, 2015, 29 : 2418 - 2421
[7] Fine-mapping of two differentiated thyroid carcinoma susceptibility loci at 9q22.33 and 14q13.3 detects novel candidate functional SNPs in Europeans from metropolitan France and Melanesians from New Caledonia
Tcheandjieu, Catherine
Lesueur, Fabienne
Sanchez, Marie
Baron-Dubourdieu, Dominique
Guizard, Anne-Valerie
Mulot, Claire
Laurent-Puig, Pierre
Schvartz, Claire
Truong, Therese
Guenel, Pascal
INTERNATIONAL JOURNAL OF CANCER, 2016, 139 (03) : 617 - 627
[8] Common genetic variant on 14q13.3 contributes to thyroid cancer susceptibility: evidence based on 12 studies
JiaoJiao Zheng
Chen Li
Cong Wang
Zhilong Ai
Molecular Genetics and Genomics, 2015, 290 : 1125 - 1133
[9] Common genetic variant on 14q13.3 contributes to thyroid cancer susceptibility: evidence based on 12 studies
Zheng, JiaoJiao
Li, Chen
Wang, Cong
Ai, Zhilong
MOLECULAR GENETICS AND GENOMICS, 2015, 290 (03) : 1125 - 1133
[10] Frequent loss of heterozygosity at 14q13.3 in lung cancer
Lutz, Dionne
Sapkar, Jana
Lopez-Barcons, Lluis
Keller, Steven
Perez-Soler, Roman
Locker, Joseph
CANCER RESEARCH, 2006, 66 (08)

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