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

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.

SUBMITTER: Kiemeney LA 

PROVIDER: S-EPMC2923020 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature

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

Kiemeney Lambertus A LA   Sulem Patrick P   Besenbacher Soren S   Vermeulen Sita H SH   Sigurdsson Asgeir A   Thorleifsson Gudmar G   Gudbjartsson Daniel F DF   Stacey Simon N SN   Gudmundsson Julius J   Zanon Carlo C   Kostic Jelena J   Masson Gisli G   Bjarnason Hjordis H   Palsson Stefan T ST   Skarphedinsson Oskar B OB   Gudjonsson Sigurjon A SA   Witjes J Alfred JA   Grotenhuis Anne J AJ   Verhaegh Gerald W GW   Bishop D Timothy DT   Sak Sei Chung SC   Choudhury Ananya A   Elliott Faye F   Barrett Jennifer H JH   Hurst Carolyn D CD   de Verdier Petra J PJ   Ryk Charlotta C   Rudnai Peter P   Gurzau Eugene E   Koppova Kvetoslava K   Vineis Paolo P   Polidoro Silvia S   Guarrera Simonetta S   Sacerdote Carlotta C   Campagna Marcello M   Placidi Donatella D   Arici Cecilia C   Zeegers Maurice P MP   Kellen Eliane E   Gutierrez Berta Saez BS   Sanz-Velez José I JI   Sanchez-Zalabardo Manuel M   Valdivia Gabriel G   Garcia-Prats Maria D MD   Hengstler Jan G JG   Blaszkewicz Meinolf M   Dietrich Holger H   Ophoff Roel A RA   van den Berg Leonard H LH   Alexiusdottir Kristin K   Kristjansson Kristleifur K   Geirsson Gudmundur G   Nikulasson Sigfus S   Petursdottir Vigdis V   Kong Augustine A   Thorgeirsson Thorgeir T   Mungan N Aydin NA   Lindblom Annika A   van Es Michael A MA   Porru Stefano S   Buntinx Frank F   Golka Klaus K   Mayordomo José I JI   Kumar Rajiv R   Matullo Giuseppe G   Steineck Gunnar G   Kiltie Anne E AE   Aben Katja K H KK   Jonsson Eirikur E   Thorsteinsdottir Unnur U   Knowles Margaret A MA   Rafnar Thorunn T   Stefansson Kari K  

Nature genetics 20100328 5

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  ...[more]

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