title: Genome-wide association study identifies multiple loci associated with bladder cancer risk.
abstract: Candidate gene and genome-wide association studies (GWAS) have identified 11 independent susceptibility loci associated with bladder cancer risk. To discover additional risk variants, we conducted a new GWAS of 2422 bladder cancer cases and 5751 controls, followed by a meta-analysis with two independently published bladder cancer GWAS, resulting in a combined analysis of 6911 cases and 11 814 controls of European descent. TaqMan genotyping of 13 promising single nucleotide polymorphisms with P < 1 × 10(-5) was pursued in a follow-up set of 801 cases and 1307 controls. Two new loci achieved genome-wide statistical significance: rs10936599 on 3q26.2 (P = 4.53 × 10(-9)) and rs907611 on 11p15.5 (P = 4.11 × 10(-8)). Two notable loci were also identified that approached genome-wide statistical significance: rs6104690 on 20p12.2 (P = 7.13 × 10(-7)) and rs4510656 on 6p22.3 (P = 6.98 × 10(-7)); these require further studies for confirmation. In conclusion, our study has identified new susceptibility alleles for bladder cancer risk that require fine-mapping and laboratory investigation, which could further understanding into the biological underpinnings of bladder carcinogenesis.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Jonine D
authors.initials: JD
authors.lastname: Figueroa
authors.forename: Yuanqing
authors.initials: Y
authors.lastname: Ye
authors.forename: Afshan
authors.initials: A
authors.lastname: Siddiq
authors.forename: Montserrat
authors.initials: M
authors.lastname: Garcia-Closas
authors.forename: Nilanjan
authors.initials: N
authors.lastname: Chatterjee
authors.forename: Ludmila
authors.initials: L
authors.lastname: Prokunina-Olsson
authors.forename: Victoria K
authors.initials: VK
authors.lastname: Cortessis
authors.forename: Charles
authors.initials: C
authors.lastname: Kooperberg
authors.forename: Olivier
authors.initials: O
authors.lastname: Cussenot
authors.forename: Simone
authors.initials: S
authors.lastname: Benhamou
authors.forename: Jennifer
authors.initials: J
authors.lastname: Prescott
authors.forename: Stefano
authors.initials: S
authors.lastname: Porru
authors.forename: Colin P
authors.initials: CP
authors.lastname: Dinney
authors.forename: Núria
authors.initials: N
authors.lastname: Malats
authors.forename: Dalsu
authors.initials: D
authors.lastname: Baris
authors.forename: Mark
authors.initials: M
authors.lastname: Purdue
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Jacobs
authors.forename: Demetrius
authors.initials: D
authors.lastname: Albanes
authors.forename: Zhaoming
authors.initials: Z
authors.lastname: Wang
authors.forename: Xiang
authors.initials: X
authors.lastname: Deng
authors.forename: Charles C
authors.initials: CC
authors.lastname: Chung
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
authors.forename: H
authors.initials: H
authors.lastname: Bas Bueno-de-Mesquita
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Trichopoulos
authors.forename: Börje
authors.initials: B
authors.lastname: Ljungberg
authors.forename: Françoise
authors.initials: F
authors.lastname: Clavel-Chapelon
authors.forename: Elisabete
authors.initials: E
authors.lastname: Weiderpass
authors.forename: Vittorio
authors.initials: V
authors.lastname: Krogh
authors.forename: Miren
authors.initials: M
authors.lastname: Dorronsoro
authors.forename: Ruth
authors.initials: R
authors.lastname: Travis
authors.forename: Anne
authors.initials: A
authors.lastname: Tjønneland
authors.forename: Paul
authors.initials: P
authors.lastname: Brenan
authors.forename: Jenny
authors.initials: J
authors.lastname: Chang-Claude
authors.forename: Elio
authors.initials: E
authors.lastname: Riboli
authors.forename: David
authors.initials: D
authors.lastname: Conti
authors.forename: Manuela
authors.initials: M
authors.lastname: Gago-Dominguez
authors.forename: Mariana C
authors.initials: MC
authors.lastname: Stern
authors.forename: Malcolm C
authors.initials: MC
authors.lastname: Pike
authors.forename: David
authors.initials: D
authors.lastname: Van Den Berg
authors.forename: Jian-Min
authors.initials: JM
authors.lastname: Yuan
authors.forename: Chancellor
authors.initials: C
authors.lastname: Hohensee
authors.forename: Rebecca
authors.initials: R
authors.lastname: Rodabough
authors.forename: Geraldine
authors.initials: G
authors.lastname: Cancel-Tassin
authors.forename: Morgan
authors.initials: M
authors.lastname: Roupret
authors.forename: Eva
authors.initials: E
authors.lastname: Comperat
authors.forename: Constance
authors.initials: C
authors.lastname: Chen
authors.forename: Immaculata
authors.initials: I
authors.lastname: De Vivo
authors.forename: Edward
authors.initials: E
authors.lastname: Giovannucci
authors.forename: David J
authors.initials: DJ
authors.lastname: Hunter
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
authors.forename: Sara
authors.initials: S
authors.lastname: Lindstrom
authors.forename: Angela
authors.initials: A
authors.lastname: Carta
authors.forename: Sofia
authors.initials: S
authors.lastname: Pavanello
authors.forename: Cecilia
authors.initials: C
authors.lastname: Arici
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mastrangelo
authors.forename: Ashish M
authors.initials: AM
authors.lastname: Kamat
authors.forename: Seth P
authors.initials: SP
authors.lastname: Lerner
authors.forename: H
authors.initials: H
authors.lastname: Barton Grossman
authors.forename: Jie
authors.initials: J
authors.lastname: Lin
authors.forename: Jian
authors.initials: J
authors.lastname: Gu
authors.forename: Xia
authors.initials: X
authors.lastname: Pu
authors.forename: Amy
authors.initials: A
authors.lastname: Hutchinson
authors.forename: Laurie
authors.initials: L
authors.lastname: Burdette
authors.forename: William
authors.initials: W
authors.lastname: Wheeler
authors.forename: Manolis
authors.initials: M
authors.lastname: Kogevinas
authors.forename: Adonina
authors.initials: A
authors.lastname: Tardón
authors.forename: Consol
authors.initials: C
authors.lastname: Serra
authors.forename: Alfredo
authors.initials: A
authors.lastname: Carrato
authors.forename: Reina
authors.initials: R
authors.lastname: García-Closas
authors.forename: Josep
authors.initials: J
authors.lastname: Lloreta
authors.forename: Molly
authors.initials: M
authors.lastname: Schwenn
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Karagas
authors.forename: Alison
authors.initials: A
authors.lastname: Johnson
authors.forename: Alan
authors.initials: A
authors.lastname: Schned
authors.forename: Karla R
authors.initials: KR
authors.lastname: Armenti
authors.forename: G M
authors.initials: GM
authors.lastname: Hosain
authors.forename: Gerald
authors.initials: G
authors.lastname: Andriole
authors.forename: Robert
authors.initials: R
authors.lastname: Grubb
authors.forename: Amanda
authors.initials: A
authors.lastname: Black
authors.forename: W
authors.initials: W
authors.lastname: Ryan Diver
authors.forename: Susan M
authors.initials: SM
authors.lastname: Gapstur
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Weinstein
authors.forename: Jarmo
authors.initials: J
authors.lastname: Virtamo
authors.forename: Chris A
authors.initials: CA
authors.lastname: Haiman
authors.forename: Maria T
authors.initials: MT
authors.lastname: Landi
authors.forename: Neil
authors.initials: N
authors.lastname: Caporaso
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Fraumeni
authors.forename: Paolo
authors.initials: P
authors.lastname: Vineis
authors.forename: Xifeng
authors.initials: X
authors.lastname: Wu
authors.forename: Debra T
authors.initials: DT
authors.lastname: Silverman
authors.forename: Stephen
authors.initials: S
authors.lastname: Chanock
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Rothman
mesh_terms: D016022:Case-Control Studies; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D015201:Meta-Analysis as Topic; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology