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

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 × 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 wild-type FGFR3. Our results show a link between germline variants, somatic mutations of FGFR3 and risk of UBC. © 2010 Nature America, Inc. All rights reserved.

Авторы
Kiemeney L.A.1, 2, 3 , Vermeulen S.H.1 , Grotenhuis A.J.1 , Aben K.K.H.1, 3 , Witjes J.A. 2 , Verhaegh G.W.2 , Sulem P.4 , Besenbacher S.4 , Sigurdsson A.4 , Thorleifsson G.4 , Gudbjartsson D.F.4 , Stacey S.N.4 , Gudmundsson J.4 , Zanon C.4 , Kostic J.4 , Masson G.4 , Bjarnason H.4 , Palsson S.T.4 , Skarphedinsson O.B.4 , Gudjonsson S.A.4 , Kristjansson K.4 , Kong A.4 , Thorgeirsson T.4 , Thorsteinsdottir U.4, 43 , Rafnar T.4 , Stefansson K.4, 43 , Bishop D.T.5 , Elliott F.5 , Barrett J.H.5 , Sak S.C.6 , Hurst C.D.6 , Knowles M.A.6 , Choudhury A.7 , De Verdier P.J.8 , Ryk C.8 , Rudnai P.9 , Gurzau E.10 , Koppova K.11 , Vineis P.12, 13 , Polidoro S.12, 14 , Guarrera S.12, 14 , Matullo G.12, 14 , Sacerdote C.15, 16 , Campagna M.17 , Placidi D.17 , Arici C.17 , Porru S.17 , Zeegers M.P.18, 19 , Kellen E.20 , Gutierrez B.S.21 , Sanz-Velez J.I.22 , Sanchez-Zalabardo M.23 , Valdivia G.24 , Garcia-Prats M.D.25 , Hengstler J.G.26 , Blaszkewicz M.26 , Golka K.26 , Dietrich H.27 , Ophoff R.A.28, 29 , Van Den Berg L.H.30 , Van Es M.A.30 , Alexiusdottir K.31 , Geirsson G.32 , Jonsson E.32 , Nikulasson S. 33 , Petursdottir V. 33 , Mungan N.A.34 , Lindblom A.35 , Buntinx F.36, 37 , Mayordomo J.I.38 , Kumar R.39 , Steineck G.40, 41 , Kiltie A.E.42
Журнал
Nature Genetics
Издательство
Nature Publishing Group
Номер выпуска
5
Язык
Английский
Страницы
415-419
Статус
Опубликовано
Том
42
Год
2010
Организации
  • 1 Department of Epidemiology, Biostatistics and Health Technology Assessment
  • 2 Department of Urology|Radboud University Nijmegen Medical Centre
  • 3 Comprehensive Cancer Center East
  • 4 DeCODE Genetics
  • 5 Faculty of Medicine|University of Iceland
  • 6 Section of Epidemiology and Biostatistics
  • 7 Section of Experimental Oncology|Leeds Institute of Molecular Medicine|St. James's University Hospital
  • 8 Christie Hospital National Health Service Foundation Trust
  • 9 Department of Molecular Medicine and Surgery|Karolinska Institutet
  • 10 National Institute of Environmental Health
  • 11 Environmental Health Centre
  • 12 State Health Institute
  • 13 Institute for Scientific Interchange (ISI) Foundation
  • 14 Department of Epidemiology and Public Health|Imperial College
  • 15 Department of Genetics, Biology and Biochemistry|University of Torino
  • 16 Unit of Cancer Epidemiology|University of Torino
  • 17 Centre for Cancer Epidemiology and Prevention (CPO Piemonte)
  • 18 Department of Experimental and Applied Medicine|Section of Occupational Medicine and Industrial Hygiene|University of Brescia
  • 19 Unit of Genetic Epidemiology|Department of Public Health and Epidemiology|University of Birmingham
  • 20 Department of Complex Genetics, Cluster of Genetics and Cell Biology|Nutrition and Toxicology Research Institute|Maastricht University
  • 21 Leuven University Centre for Cancer Prevention (LUCK)
  • 22 Department of Medicine|University of Zaragoza
  • 23 Division of Urology|San Jorge Hospital
  • 24 Division of Urology|Hospital Clinico
  • 25 Department of Urology|University of Zaragoza School of Medicine
  • 26 Division of Surgical Pathology|San Jorge Hospital
  • 27 Leibniz Research Centre for Working Environment and Human Factors
  • 28 Department of Urology|Paul Gerhardt Foundation
  • 29 Department of Medical Genetics|Rudolf Magnus Institute of Neuroscience|University Medical Center Utrecht
  • 30 University of California Los Angeles|Center for Neurobehavioral Genetics
  • 31 Department of Neurology|Rudolf Magnus Institute of Neuroscience|University Medical Center Utrecht
  • 32 Department of Medical Oncology
  • 33 Department of Urology
  • 34 Department of Pathology|Landspitali-University Hospital
  • 35 Department of Urology|Zonguldak Karaelmas University
  • 36 Department of Molecular Medicine and Surgery|Karolinska Institute
  • 37 Department of General Practice|Catholic University of Leuvena
  • 38 Department of General Practice|Maastricht University
  • 39 Division of Medical Oncology|University of Zaragoza
  • 40 Division of Molecular Genetic Epidemiology|German Cancer Research Centre
  • 41 Section of Clinical Cancer Epidemiology|Department of Oncology and Pathology|Karolinska Institutet
  • 42 Division of Clinical Cancer Epidemiology|Department of Oncology|Institute of Clinical Sciences
  • 43 Gray Institute for Radiation Oncology and Biology|University of Oxford
Дата создания
08.07.2024
Дата изменения
08.07.2024
Постоянная ссылка
https://repository.rudn.ru/ru/records/article/record/123301/
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