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Hum Mol Genet. 2014 Oct 15;23(20):5545-57. doi: 10.1093/hmg/ddu264. Epub 2014 May 26.

Genome-wide association study yields variants at 20p12.2 that associate with urinary bladder cancer.

Author information

1
deCODE Genetics/AMGEN, Reykjavik 101, Iceland thorunn.rafnar@decode.is kstefans@decode.is.
2
deCODE Genetics/AMGEN, Reykjavik 101, Iceland.
3
Department for Health Evidence Department of Genetics and.
4
deCODE Genetics/AMGEN, Reykjavik 101, Iceland School of Engineering and Natural Sciences and.
5
Department of Medicine.
6
Department of Pathology.
7
Department of Urology and.
8
Faculty of Medicine, University of Iceland, Reykjavik 101, Iceland Department of Surgery, Landspitali-University Hospital, Reykjavik 101, Iceland.
9
Department for Health Evidence Comprehensive Cancer Center The Netherlands, Utrecht, The Netherlands.
10
Department for Health Evidence.
11
Department of Urology, Radboud University Medical Center, Nijmegen 6500 HB, The Netherlands.
12
Division of Medical Oncolology, Marques de Valdecilla University Hospital, Santander 39008, Spain.
13
Division of Medical Oncolology, Ciudad de Coria Hospital, Coria 10800, Spain.
14
Section of Experimental Oncology, Leeds Institute of Cancer and Pathology, St. James's University Hospital, Leeds LS9 7TF, UK.
15
Section of Epidemiology & Biostatistics, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds LS2 9JT, UK.
16
Mid Yorkshire NHS Trust, Pinderfields Hospital, Wakefield WF1 4DG, UK.
17
Christie Hospital NHS Trust, Manchester M20 4BX, UK.
18
Department of Medical and Surgical Specialties, Radiological Sciences and Public Health University of Brescia, Brescia 1-25125, Italy.
19
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm S171 76, Sweden.
20
Department of Environmental Epidemiology, National Institute of Environmental Health, Budapest H-1450, Hungary.
21
Health Department, Environmental Health Center, Babes Bolyai University, Cluj-Napoca 3400, Romania.
22
Department of Environmental Health, Regional Authority of Public Health, Banska Bystrica 975 56, Slovakia.
23
Department of Pathology, Erasmus MC, Rotterdam 3000 CA, The Netherlands.
24
Department of General Practice, Catholic University of Leuven, Leuven 3000, Belgium.
25
Leuven University Centre for Cancer Prevention (LUCK), Leuven 3000, Belgium.
26
Human Genetics Foundation, HuGeF, Torino I-10126, Italy.
27
Human Genetics Foundation, HuGeF, Torino I-10126, Italy Department of Medical Sciences and.
28
Human Genetics Foundation, HuGeF, Torino I-10126, Italy Unit of Cancer Epidemiology, University of Torino, Torino 10126, Italy Centre for Cancer Epidemiology and Prevention (CPO Piemonte), Torino 10126, Italy.
29
Human Genetics Foundation, HuGeF, Torino I-10126, Italy Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
30
CNRS, UMR 144, Oncologie Moléculaire, Institut Curie, Paris 75248 Cedex 05, France Institut Curie, Centre de Recherche, Paris 75248 Cedex 05, France.
31
Department of Epidemiology & Complex Genetics NUTRIM/Faculty of Health, Medicine and Life Sciences Maastricht University, Maastricht 6200 MD, The Netherlands.
32
Department of Urology, Lukasklinik Neuss, Preussenstr. 64, Neuss 41464, Germany.
33
Department of Urology, St.-Josefs-Hospital Dortmund-Hörde, Dortmund 44263, Germany.
34
Department of Urology, Evangelisches Krankenhaus Paul Gerhardt Foundation, Lutherstadt Wittenberg 06886, Germany.
35
Leibniz Research Centre for Working Environment and Human Factors, Dortmund 44139, Germany.
36
Department of General Practice, Catholic University of Leuven, Leuven 3000, Belgium Research School Care & Department of General Practice, Maastricht University, Maastricht 6200 MD, The Netherlands.
37
Division of Molecular Genetic Epidemiology, German Cancer Research Centre, Heidelberg D-69120, Germany.
38
Division of Medical Oncology, University of Zaragoza, Zaragoza 50009, Spain.
39
Department of Oncology and Pathology, Karolinska Hospital, Stockholm S171 76, Sweden Department of Oncology, Sahlgrenska University Hospital, Goteborg S-413 45, Sweden.
40
Gray Institute for Radiation Oncology and Biology, Department of Oncology, University of Oxford, Oxford OX3 7DQ, UK.
41
deCODE Genetics/AMGEN, Reykjavik 101, Iceland Faculty of Medicine, University of Iceland, Reykjavik 101, Iceland.
42
Department for Health Evidence Department of Urology, Radboud University Medical Center, Nijmegen 6500 HB, The Netherlands.
43
deCODE Genetics/AMGEN, Reykjavik 101, Iceland Faculty of Medicine, University of Iceland, Reykjavik 101, Iceland thorunn.rafnar@decode.is kstefans@decode.is.

Abstract

Genome-wide association studies (GWAS) of urinary bladder cancer (UBC) have yielded common variants at 12 loci that associate with risk of the disease. We report here the results of a GWAS of UBC including 1670 UBC cases and 90 180 controls, followed by replication analysis in additional 5266 UBC cases and 10 456 controls. We tested a dataset containing 34.2 million variants, generated by imputation based on whole-genome sequencing of 2230 Icelanders. Several correlated variants at 20p12, represented by rs62185668, show genome-wide significant association with UBC after combining discovery and replication results (OR = 1.19, P = 1.5 × 10(-11) for rs62185668-A, minor allele frequency = 23.6%). The variants are located in a non-coding region approximately 300 kb upstream from the JAG1 gene, an important component of the Notch signaling pathways that may be oncogenic or tumor suppressive in several forms of cancer. Our results add to the growing number of UBC risk variants discovered through GWAS.

PMID:
24861552
DOI:
10.1093/hmg/ddu264
[Indexed for MEDLINE]
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