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

2.50
Hdl Handle:
http://hdl.handle.net/10146/113399
Title:
A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer.
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
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
Issue Date:
May-2010
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.
Appears in Collections:
Articles

Full metadata record

DC FieldValue Language
dc.contributor.authorKiemeney, Lambertus A.en
dc.contributor.authorSulem, Patricken
dc.contributor.authorBesenbacher, Sorenen
dc.contributor.authorVermeulen, Sita H.en
dc.contributor.authorSigurdsson, Asgeiren
dc.contributor.authorThorleifsson, Gudmaren
dc.contributor.authorGudbjartsson, Daniel F.en
dc.contributor.authorStacey, Simon N.en
dc.contributor.authorGudmundsson, Juliusen
dc.contributor.authorZanon, Carloen
dc.contributor.authorKostic, Jelenaen
dc.contributor.authorMasson, Gislien
dc.contributor.authorBjarnason, Hjordisen
dc.contributor.authorPalsson, Stefan T.en
dc.contributor.authorSkarphedinsson, Oskar B.en
dc.contributor.authorGudjonsson, Sigurjon A.en
dc.contributor.authorWitjes, J. Alfreden
dc.contributor.authorGrotenhuis, Anne J.en
dc.contributor.authorVerhaegh, Gerald W.en
dc.contributor.authorBishop, D. Timothyen
dc.contributor.authorSak, Sei Chungen
dc.contributor.authorChoudhury, Ananyaen
dc.contributor.authorElliott, Fayeen
dc.contributor.authorBarrett, Jennifer H.en
dc.contributor.authorHurst, Carolyn D.en
dc.contributor.authorde Verdier, Petra J.en
dc.contributor.authorRyk, Charlottaen
dc.contributor.authorRudnai, Peteren
dc.contributor.authorGurzau, Eugeneen
dc.contributor.authorKoppova, Kvetoslavaen
dc.contributor.authorVineis, Paoloen
dc.contributor.authorPolidoro, Silviaen
dc.contributor.authorGuarrera, Simonettaen
dc.contributor.authorSacerdote, Carlottaen
dc.contributor.authorCampagna, Marcelloen
dc.contributor.authorPlacidi, Donatellaen
dc.contributor.authorArici, Ceciliaen
dc.contributor.authorZeegers, Maurice P.en
dc.contributor.authorKellen, Elianeen
dc.contributor.authorGutierrez, Berta Saezen
dc.contributor.authorSanz-Velez, José I.en
dc.contributor.authorSanchez-Zalabardo, Manuelen
dc.contributor.authorValdivia, Gabrielen
dc.contributor.authorGarcia-Prats, Maria D.en
dc.contributor.authorHengstler, Jan G.en
dc.contributor.authorBlaszkewicz, Meinolfen
dc.contributor.authorDietrich, Holgeren
dc.contributor.authorOphoff, Roel A.en
dc.contributor.authorvan den Berg, Leonard H.en
dc.contributor.authorAlexiusdottir, Kristinen
dc.contributor.authorKristjansson, Kristleifuren
dc.contributor.authorGeirsson, Gudmunduren
dc.contributor.authorNikulasson, Sigfusen
dc.contributor.authorPetursdottir, Vigdisen
dc.contributor.authorKong, Augustineen
dc.contributor.authorThorgeirsson, Thorgeiren
dc.contributor.authorMungan, N. Aydinen
dc.contributor.authorLindblom, Annikaen
dc.contributor.authorvan Es, Michael A.en
dc.contributor.authorPorru, Stefanoen
dc.contributor.authorBuntinx, Franken
dc.contributor.authorGolka, Klausen
dc.contributor.authorMayordomo, José I.en
dc.contributor.authorKumar, Rajiven
dc.contributor.authorMatullo, Giuseppeen
dc.contributor.authorSteineck, Gunnaren
dc.contributor.authorKiltie, Anne E.en
dc.contributor.authorAben, Katja K.H.en
dc.contributor.authorJonsson, Eirikuren
dc.contributor.authorThorsteinsdottir, Unnuren
dc.contributor.authorKnowles, Margaret A.en
dc.contributor.authorRafnar, Thorunnen
dc.contributor.authorStefansson, Karien
dc.date.accessioned2010-10-18T13:47:07Z-
dc.date.available2010-10-18T13:47:07Z-
dc.date.issued2010-05-
dc.identifier.citationNat. Genet. 2010, 42 (5):415-419en
dc.identifier.issn1546-1718-
dc.identifier.pmid20348956-
dc.identifier.doi10.1038/ng.558-
dc.identifier.urihttp://hdl.handle.net/10146/113399-
dc.description.abstractPreviously, 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.en
dc.description.sponsorshipThe 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.en
dc.language.isoenen
dc.relation.urlhttp://www.nature.com/ng/journal/v42/n5/full/ng.558.htmlen
dc.subjectUrinary Bladder Neoplasmsen
dc.subjectSmokingen
dc.subjectMutationen
dc.subjectHumansen
dc.subjectGenotypeen
dc.subjectAllelesen
dc.subjectDisease-Free Survivalen
dc.subjectEuropeen
dc.subject.meshAlleles-
dc.subject.meshChromosomes, Human, Pair 4-
dc.subject.meshDisease-Free Survival-
dc.subject.meshEurope-
dc.subject.meshFemale-
dc.subject.meshGenetic Predisposition to Disease-
dc.subject.meshGenetic Variation-
dc.subject.meshGenotype-
dc.subject.meshHumans-
dc.subject.meshMale-
dc.subject.meshModels, Genetic-
dc.subject.meshMutation-
dc.subject.meshReceptor, Fibroblast Growth Factor, Type 3-
dc.subject.meshRecurrence-
dc.subject.meshRisk-
dc.subject.meshSmoking-
dc.subject.meshUrinary Bladder Neoplasms-
dc.titleA sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer.en
dc.typeArticleen
dc.identifier.journalNature Geneticsen

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