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

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    Authors
    Kiemeney, Lambertus A.
    Sulem, Patrick
    Besenbacher, Soren
    Vermeulen, Sita H.
    Sigurdsson, Asgeir
    Thorleifsson, Gudmar
    Gudbjartsson, Daniel F.
    Stacey, Simon N.
    Gudmundsson, Julius
    Zanon, Carlo
    Kostic, Jelena
    Masson, Gisli
    Bjarnason, Hjordis
    Palsson, Stefan T.
    Skarphedinsson, Oskar B.
    Gudjonsson, Sigurjon A.
    Witjes, J. Alfred
    Grotenhuis, Anne J.
    Verhaegh, Gerald W.
    Bishop, D. Timothy
    Sak, Sei Chung
    Choudhury, Ananya
    Elliott, Faye
    Barrett, Jennifer H.
    Hurst, Carolyn D.
    de Verdier, Petra J.
    Ryk, Charlotta
    Rudnai, Peter
    Gurzau, Eugene
    Koppova, Kvetoslava
    Vineis, Paolo
    Polidoro, Silvia
    Guarrera, Simonetta
    Sacerdote, Carlotta
    Campagna, Marcello
    Placidi, Donatella
    Arici, Cecilia
    Zeegers, Maurice P.
    Kellen, Eliane
    Gutierrez, Berta Saez
    Sanz-Velez, José I.
    Sanchez-Zalabardo, Manuel
    Valdivia, Gabriel
    Garcia-Prats, Maria D.
    Hengstler, Jan G.
    Blaszkewicz, Meinolf
    Dietrich, Holger
    Ophoff, Roel A.
    van den Berg, Leonard H.
    Alexiusdottir, Kristin
    Kristjansson, Kristleifur
    Geirsson, Gudmundur
    Nikulasson, Sigfus
    Petursdottir, Vigdis
    Kong, Augustine
    Thorgeirsson, Thorgeir
    Mungan, N. Aydin
    Lindblom, Annika
    van Es, Michael A.
    Porru, Stefano
    Buntinx, Frank
    Golka, Klaus
    Mayordomo, José I.
    Kumar, Rajiv
    Matullo, Giuseppe
    Steineck, Gunnar
    Kiltie, Anne E.
    Aben, Katja K.H.
    Jonsson, Eirikur
    Thorsteinsdottir, Unnur
    Knowles, Margaret A.
    Rafnar, Thorunn
    Stefansson, Kari
    Issue Date
    2010-05
    
    Metadata
    Show full item record
    Abstract
    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 wild-type FGFR3. Our results show a link between germline variants, somatic mutations of FGFR3 and risk of UBC.
    Citation
    Nat. Genet. 2010, 42 (5):415-419
    Journal
    Nature Genetics
    URI
    http://hdl.handle.net/10146/113399
    DOI
    10.1038/ng.558
    PubMed ID
    20348956
    Additional Links
    http://www.nature.com/ng/journal/v42/n5/full/ng.558.html
    Type
    Article
    Language
    en
    ISSN
    1546-1718
    Sponsors
    The Torino Bladder Cancer Case Control Study was supported by a grant to ECNIS (Environmental Cancer Risk, Nutrition and Individual Susceptibility), a network of excellence operating within the European Union Sixth Framework Program, Priority 5: ‘Food Quality and Safety’ (Contract No. 513943), and by grants of the Compagnia di San Paolo, of the Italian Association for Cancer Research and of the Piedmont Region Progetti de Ricerca Sanitaria Finalizzata, Italy. The Belgian case-control study on bladder cancer risk was supported by a grant of the Flemish government, the government of the Belgian province of Limburg and the Limburg Cancer Fund.
    ae974a485f413a2113503eed53cd6c53
    10.1038/ng.558
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