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 27 条

[1] Cancer as a complex phenotype: Pattern of cancer distribution within and beyond the nuclear family
Amundadottir, LT
Thorvaldsson, S
Gudbjartsson, DF
Sulem, P
Kristjansson, K
Arnason, S
Gulcher, JR
Bjornsson, J
Kong, A
Thorsteinsdottir, U
Stefansson, K
[J]. PLOS MEDICINE, 2004, 1 (03) : 229 - 236
[2] Strong association of chromosome 1p12 loci with thyroid cancer susceptibility
Baida, Aida
Akdi, Mounaim.
Gonzalez-Flores, Eddy
Galofre, Pere
Marcos, Ricard
Velazquez, Antonia
[J]. CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, 2008, 17 (06) : 1499 - 1504
[3] Mutation of the gene encoding human TTF-2 associated with thyroid agenesis, cleft palate and choanal atresia
Clifton-Bligh, RJ
Wentworth, JM
Heinz, P
Crisp, MS
John, R
Lazarus, JH
Ludgate, M
Chatterjee, VK
[J]. NATURE GENETICS, 1998, 19 (04) : 399 - 401
[4] Environmental and heritable causes of cancer among 9.6 million individuals in the Swedish family-cancer database
Czene, K
Lichtenstein, P
Hemminki, K
[J]. INTERNATIONAL JOURNAL OF CANCER, 2002, 99 (02) : 260 - 266
[5] Distribution of the titf2/foxe1 gene product is consistent with an important role in the development of foregut endoderm, palate, and hair
Dathan, N
Parlato, R
Rosica, A
De Felice, M
Di Lauro, R
[J]. DEVELOPMENTAL DYNAMICS, 2002, 224 (04) : 450 - 456
[6] A mouse model for hereditary thyroid dysgenesis and cleft palate
De Felice, M
Ovitt, C
Biffali, E
Rodriguez-Mallon, A
Arra, C
Anastassiadis, K
Macchia, PE
Mattei, MG
Mariano, A
Schöler, H
Macchia, V
Di Lauro, R
[J]. NATURE GENETICS, 1998, 19 (04) : 395 - 398
[7] Pathology and genetics of thyroid carcinoma
Delellis, Ronald A.
[J]. JOURNAL OF SURGICAL ONCOLOGY, 2006, 94 (08) : 662 - 669
[8] Genomic control for association studies
Devlin, B
Roeder, K
[J]. BIOMETRICS, 1999, 55 (04) : 997 - 1004
[9] HAPLOTYPE RELATIVE RISKS - AN EASY RELIABLE WAY TO CONSTRUCT A PROPER CONTROL SAMPLE FOR RISK CALCULATIONS
FALK, CT
RUBINSTEIN, P
[J]. ANNALS OF HUMAN GENETICS, 1987, 51 : 227 - 233
[10] SYSTEMATIC POPULATION-BASED ASSESSMENT OF CANCER RISK IN FIRST-DEGREE RELATIVES OF CANCER PROBANDS
GOLDGAR, DE
EASTON, DF
CANNONALBRIGHT, LA
SKOLNICK, MH
[J]. JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1994, 86 (21) : 1600 - 1608

← 1 2 3 →