A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.

Authors:
Dr. Jonine Figueroa, PhD
Dr. Jonine Figueroa, PhD
Usher Institute of Population Health Sciences and Informatics
Chancellor's Fellow
Molecular epidemiology
Edinburgh, Scotland | United Kingdom
Nathaniel Rothman Montserrat Garcia-Closas Nilanjan Chatterjee Nuria Malats Xifeng Wu Jonine D Figueroa Francisco X Real David Van Den Berg Giuseppe Matullo Dalsu Baris Michael Thun Lambertus A Kiemeney Paolo Vineis Immaculata De Vivo Demetrius Albanes Mark P Purdue Thorunn Rafnar Michelle A T Hildebrandt Anne E Kiltie Olivier Cussenot Klaus Golka Rajiv Kumar Jack A Taylor Jose I Mayordomo Kevin B Jacobs Manolis Kogevinas Amy Hutchinson Zhaoming Wang Yi-Ping Fu Ludmila Prokunina-Olsson Laurie Burdett Meredith Yeager William Wheeler Adonina Tardón Consol Serra Alfredo Carrato Reina García-Closas Josep Lloreta Alison Johnson Molly Schwenn Margaret R Karagas Alan Schned Gerald Andriole Robert Grubb Amanda Black Eric J Jacobs W Ryan Diver Susan M Gapstur Stephanie J Weinstein Jarmo Virtamo Victoria K Cortessis Manuela Gago-Dominguez Malcolm C Pike Mariana C Stern Jian-Min Yuan David J Hunter Monica McGrath Colin P Dinney Bogdan Czerniak Meng Chen Hushan Yang Sita H Vermeulen Katja K Aben J Alfred Witjes Remco R Makkinje Patrick Sulem Soren Besenbacher Kari Stefansson Elio Riboli Paul Brennan Salvatore Panico Carmen Navarro Naomi E Allen H Bas Bueno-de-Mesquita Dimitrios Trichopoulos Neil Caporaso Maria Teresa Landi Federico Canzian Borje Ljungberg Anne Tjonneland Francoise Clavel-Chapelon David T Bishop Mark T W Teo Margaret A Knowles Simonetta Guarrera Silvia Polidoro Fulvio Ricceri Carlotta Sacerdote Alessandra Allione Geraldine Cancel-Tassin Silvia Selinski Jan G Hengstler Holger Dietrich Tony Fletcher Peter Rudnai Eugen Gurzau Kvetoslava Koppova Sophia C E Bolick Ashley Godfrey Zongli Xu José I Sanz-Velez María D García-Prats Manuel Sanchez Gabriel Valdivia Stefano Porru Simone Benhamou Robert N Hoover Joseph F Fraumeni Debra T Silverman Stephen J Chanock

Nat Genet 2010 Nov 24;42(11):978-84. Epub 2010 Oct 24.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.

We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis.

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http://dx.doi.org/10.1038/ng.687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3049891PMC
November 2010
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References

(Supplied by CrossRef)
Article in Int. J. Cancer
AF Kantor et al.
Int. J. Cancer 1985
Article in Cancer Epidemiol. Biomarkers Prev.
C Murta-Nascimento et al.
Cancer Epidemiol. Biomarkers Prev. 2007
Article in Eur. J. Cancer
KK Aben et al.
Eur. J. Cancer 2006
Article in Environ. Health Perspect.
GM Lower Jr. et al.
Environ. Health Perspect. 1979
Article in J. Natl. Cancer Inst.
DA Bell et al.
J. Natl. Cancer Inst. 1993
Article in Lancet
M García-Closas et al.
Lancet 2005
Article in Int. J. Epidemiol.
N Rothman et al.
Int. J. Epidemiol. 2007
Article in Nat. Genet.
LA Kiemeney et al.
Nat. Genet. 2008
Article in Nat. Genet.
LA Kiemeney et al.
Nat. Genet. 2010
Article in Nat. Genet.
X Wu et al.
Nat. Genet. 2009

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