A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer

被引：143

作者：

Kiemeney, Lambertus A. ^{[1
,2
,3
]}

Sulem, Patrick ^{[4
]}

Besenbacher, Soren ^{[4
]}

Vermeulen, Sita H. ^{[1
]}

Sigurdsson, Asgeir ^{[4
]}

Thorleifsson, Gudmar ^{[4
]}

Gudbjartsson, Daniel F. ^{[4
]}

Stacey, Simon N. ^{[4
]}

Gudmundsson, Julius ^{[4
]}

Zanon, Carlo

Kostic, Jelena ^{[4
]}

Masson, Gisli ^{[4
]}

Bjarnason, Hjordis ^{[4
]}

Palsson, Stefan T. ^{[4
]}

Skarphedinsson, Oskar B. ^{[4
]}

Gudjonsson, Sigurjon A. ^{[4
]}

Witjes, J. Alfred ^{[2
]}

Grotenhuis, Anne J. ^{[1
]}

Verhaegh, Gerald W. ^{[2
]}

Bishop, D. Timothy ^{[5
]}

Sak, Sei Chung ^{[6
]}

Choudhury, Ananya ^{[7
]}

Elliott, Faye ^{[5
]}

Barrett, Jennifer H. ^{[5
]}

Hurst, Carolyn D. ^{[6
]}

de Verdier, Petra J. ^{[8
]}

Ryk, Charlotta ^{[8
]}

Rudnai, Peter ^{[9
]}

Gurzau, Eugene ^{[10
]}

Koppova, Kvetoslava ^{[11
]}

Vineis, Paolo ^{[12
,13
]}

Polidoro, Silvia ^{[12
,14
]}

Guarrera, Simonetta ^{[12
,14
]}

Sacerdote, Carlotta ^{[15
,16
]}

Campagna, Marcello ^{[17
]}

Placidi, Donatella ^{[17
]}

Arici, Cecilia ^{[17
]}

Zeegers, Maurice P. ^{[18
,19
]}

Kellen, Eliane ^{[20
]}

Saez Gutierrez, Berta ^{[21
]}

Sanz-Velez, Jose I. ^{[22
]}

Sanchez-Zalabardo, Manuel ^{[23
]}

Valdivia, Gabriel ^{[24
]}

Garcia-Prats, Maria D. ^{[25
]}

Hengstler, Jan G. ^{[26
]}

Blaszkewicz, Meinolf ^{[26
]}

Dietrich, Holger ^{[27
]}

Ophoff, Roel A. ^{[28
,29
]}

van den Berg, Leonard H. ^{[30
]}

Alexiusdottir, Kristin ^{[31
]}

机构：

[1] Radboud Univ Nijmegen, Med Ctr, Dept Epidemiol Biostat & Hlth Technol Assessment, NL-6525 ED Nijmegen, Netherlands

[2] Radboud Univ Nijmegen, Med Ctr, Dept Urol, NL-6525 ED Nijmegen, Netherlands

[3] Comprehens Canc Ctr E, Nijmegen, Netherlands

[4] deCODE Genet, Reykjavik, Iceland

[5] St James Univ Hosp, Epidemiol & Biostat Sect, Leeds, W Yorkshire, England

[6] St James Univ Hosp, Leeds Inst Mol Med, Sect Expt Oncol, Leeds, W Yorkshire, England

[7] Christie Hosp Natl Hlth Serv Fdn Trust, Manchester, Lancs, England

[8] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden

[9] Natl Inst Environm Hlth, Budapest, Hungary

[10] Ctr Environm Hlth, Cluj Napoca, Romania

[11] State Hlth Inst, Banska Bystrica, Slovakia

[12] Inst Sci Interchange ISI Fdn, Turin, Italy

[13] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Publ Hlth, London, England

[14] Univ Turin, Dept Genet Biol & Biochem, Turin, Italy

[15] Univ Turin, Unit Canc Epidemiol, Turin, Italy

[16] CPO Piemonte, Ctr Canc Epidemiol & Prevent, Turin, Italy

[17] Univ Brescia, Dept Expt & Appl Med, Sect Occupat Med & Ind Hyg, Brescia, Italy

[18] Univ Birmingham, Dept Publ Hlth & Epidemiol, Unit Genet Epidemiol, Birmingham, W Midlands, England

[19] Maastricht Univ, Nutr & Toxicol Res Inst, Cluster Genet & Cell Biol, Dept Complex Genet, Maastricht, Netherlands

[20] Leuven Univ Ctr Canc Prevent LUCK, Leuven, Belgium

[21] Univ Zaragoza, Dept Med, Zaragoza, Spain

[22] San Jorge Hosp, Div Urol, Huesca, Spain

[23] Hosp Clin, Div Urol, Zaragoza, Spain

[24] Univ Zaragoza, Sch Med, Dept Urol, Zaragoza, Spain

[25] San Jorge Hosp, Div Surg Pathol, Huesca, Spain

[26] Leibniz Res Ctr Working Environm & Human Factors, Dortmund, Germany

[27] Paul Gerhardt Fdn, Dept Urol, Lutherstadt Wittenberg, Germany

[28] Univ Med Ctr Utrecht, Dept Med Genet, Rudolf Magnus Inst Neurosci, Utrecht, Netherlands

[29] Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA USA

[30] Univ Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, Dept Neurol, Utrecht, Netherlands

[31] Landspitali Univ Hosp, Dept Med Oncol, Reykjavik, Iceland

[32] Landspitali Univ Hosp, Dept Urol, Reykjavik, Iceland

[33] Landspitali Univ Hosp, Dept Pathol, Reykjavik, Iceland

[34] Zonguldak Karaelmas Univ, Dept Urol, Zonguldak, Turkey

[35] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden

[36] Katholieke Univ Leuven, Dept Gen Practice, Leuven, Belgium

[37] Maastricht Univ, Dept Gen Practice, Maastricht, Netherlands

[38] Univ Zaragoza, Div Med Oncol, Zaragoza, Spain

[39] German Canc Res Ctr, Div Mol Genet Epidemiol, D-6900 Heidelberg, Germany

[40] Karolinska Inst, Dept Pathol & Oncol, Sect Clin Canc Epidemiol, Stockholm, Sweden

[41] Sahlgrens Acad, Inst Clin Sci, Dept Oncol, Div Clin Canc Epidemiol, Gothenburg, Sweden

[42] Univ Oxford, Gray Inst Radiat Oncol & Biol, Oxford, England

[43] Univ Iceland, Fac Med, Reykjavik, Iceland

来源：

NATURE GENETICS | 2010年 / 42卷 / 05期

关键词：

UROTHELIAL CELL-CARCINOMA; FGFR3; MUTATIONS; DISEASE; RISK; EXPRESSION;

D O I：

10.1038/ng.558

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Previously, we reported germline DNA variants associated with risk of urinary bladder cancer (UBC) in Dutch and Icelandic subjects. Here we expanded the Icelandic sample set and tested the top 20 markers from the combined analysis in several European case-control sample sets, with a total of 4,739 cases and 45,549 controls. The T allele of rs798766 on 4p16.3 was found to associate with UBC (odds ratio = 1.24, P = 9.9 x 10(-12)). rs798766 is located in an intron of TACC3, 70 kb from FGFR3, which often harbors activating somatic mutations in low-grade, noninvasive UBC. Notably, rs798766[T] shows stronger association with low-grade and low-stage UBC than with more aggressive forms of the disease and is associated with higher risk of recurrence in low-grade stage Ta tumors. The frequency of rs798766[T] is higher in Ta tumors that carry an activating mutation in FGFR3 than in Ta tumors with wildtype FGFR3. Our results show a link between germline variants, somatic mutations of FGFR3 and risk of UBC.

引用

页码：415 / U67

页数：7

共 28 条

[1] Familial aggregation of urothelial cell carcinoma
Aben, KKH
Witjes, JA
Schoenberg, MP
Hulsberger-van de Kaa, C
Verbeek, ALM
Kiemeney, LALM
[J]. INTERNATIONAL JOURNAL OF CANCER, 2002, 98 (02) : 274 - 278
[2] Occupational Exposure to Polycyclic Aromatic Hydrocarbons Influenced Neither the Frequency Nor the Spectrum of FGFR3 Mutations in Bladder Urothelial Carcinoma
Bakkar, Ashraf A.
Allory, Yves
Iwatsubo, Yuriko
de Medina, Sixtina Gil Diez
Maille, Pascale
Khreich, Nathalie
Riou, Audrey
Leroy, Karen
Vordos, Dimitrios
Abbou, Claude C.
Andujar, Pascal
Billebaud, Thierry
Chammings, Soizick
Conso, Francoise
De La Taille, Alexandre
Fontaine, Eric
Gattegno, Bernard
Ravery, Vincent
Sibony, Mathilde
Radvanyi, Francois
Chopin, Dominique K.
Pairon, Jean-Claude
[J]. MOLECULAR CARCINOGENESIS, 2010, 49 (01) : 25 - 31
[3] Frequent FGFR3 mutations in papillary non-invasive bladder (pTa) tumors
Billerey, C
Chopin, D
Aubriot-Lorton, MH
Ricol, D
de Medina, SGD
Van Rhijn, B
Bralet, MP
Lefrere-Belda, MA
Lahaye, JB
Abbou, CC
Bonaventure, J
Zafrani, ES
van der Kwast, T
Thiery, JP
Radvanyi, F
[J]. AMERICAN JOURNAL OF PATHOLOGY, 2001, 158 (06) : 1955 - 1959
[4] Frequent activating mutations of FGFR3 in human bladder and cervix carcinomas
Cappellen, D
De Oliveira, C
Ricol, D
de Medina, SGD
Bourdin, J
Sastre-Garau, X
Chopin, D
Thiery, JP
Radvanyi, F
[J]. NATURE GENETICS, 1999, 23 (01) : 18 - 20
[5] Distinct MicroRNA Alterations Characterize High- and Low-Grade Bladder Cancer
Catto, James W. F.
Miah, Saiful
Owen, Helen C.
Bryant, Helen
Myers, Katie
Dudziec, Ewa
Larre, Stephane
Milo, Marta
Rehman, Ishtiaq
Rosario, Derek J.
Di Martino, Erica
Knowles, Margaret A.
Meuth, Mark
Harris, Adrian L.
Hamdy, Freddie C.
[J]. CANCER RESEARCH, 2009, 69 (21) : 8472 - 8481
[6] Genomic control for association studies
Devlin, B
Roeder, K
[J]. BIOMETRICS, 1999, 55 (04) : 997 - 1004
[7] Genetics of gene expression and its effect on disease
Emilsson, Valur
Thorleifsson, Gudmar
Zhang, Bin
Leonardson, Amy S.
Zink, Florian
Zhu, Jun
Carlson, Sonia
Helgason, Agnar
Walters, G. Bragi
Gunnarsdottir, Steinunn
Mouy, Magali
Steinthorsdottir, Valgerdur
Eiriksdottir, Gudrun H.
Bjornsdottir, Gyda
Reynisdottir, Inga
Gudbjartsson, Daniel
Helgadottir, Anna
Jonasdottir, Aslaug
Jonasdottir, Adalbjorg
Styrkarsdottir, Unnur
Gretarsdottir, Solveig
Magnusson, Kristinn P.
Stefansson, Hreinn
Fossdal, Ragnheidur
Kristjansson, Kristleifur
Gislason, Hjortur G.
Stefansson, Tryggvi
Leifsson, Bjorn G.
Thorsteinsdottir, Unnur
Lamb, John R.
Gulcher, Jeffrey R.
Reitman, Marc L.
Kong, Augustine
Schadt, Eric E.
Stefansson, Kari
[J]. NATURE, 2008, 452 (7186) : 423 - U2
[8] The World Health Organization International Society of Urological Pathology consensus classification of urothelial (transitional cell) neoplasms of the urinary bladder
Epstein, JI
Amin, MB
Reuter, VR
Mostofi, FK
[J]. AMERICAN JOURNAL OF SURGICAL PATHOLOGY, 1998, 22 (12) : 1435 - 1448
[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] The gene encoding phosphodiesterase 4D confers risk of ischemic stroke
Gretarsdottir, S
Thorleifsson, G
Reynisdottir, ST
Manolescu, A
Jonsdottir, S
Jonsdottir, T
Gudmundsdottir, T
Bjarnadottir, SM
Einarsson, OB
Gudjonsdottir, HM
Hawkins, M
Gudmundsson, G
Gudmundsdottir, H
Andrason, H
Gudmundsdottir, AS
Sigurdardottir, M
Chou, TT
Nahmias, J
Goss, S
Sveinbjörnsdottir, S
Valdimarsson, EM
Jakobsson, F
Agnarsson, U
Gudnason, V
Thorgeirsson, G
Fingerle, J
Gurney, M
Gudbjartsson, D
Frigge, ML
Kong, A
Stefansson, K
Gulcher, JR
[J]. NATURE GENETICS, 2003, 35 (02) : 131 - 138

← 1 2 3 →