Journal
NATURE GENETICS
Volume 42, Issue 5, Pages 415-U67Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.558
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Funding
- FP7-MC-IAPP Grant [218071]
- European Commission [POLYGENE: LSHC-CT-2005]
- Radboud University Nijmegen Medical Centre
- US National Institute of Mental Health
- Cancer Research UK and Yorkshire Cancer Research
- ECNIS (Environmental Cancer Risk, Nutrition and Individual Susceptibility)
- European Union
- Priority 5: 'Food Quality and Safety' [513943]
- Compagnia di San Paolo
- Italian Association for Cancer Research and of the Piedmont Region Progetti de Ricerca Sanitaria Finalizzata, Italy
- Cancer Research UK [12933, 10589] Funding Source: researchfish
- Medical Research Council [G0801056B] Funding Source: researchfish
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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.
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