title: Polymorphisms in DNA repair genes, smoking, and bladder cancer risk: findings from the international consortium of bladder cancer.
abstract: Tobacco smoking is the most important and well-established bladder cancer risk factor and a rich source of chemical carcinogens and reactive oxygen species that can induce damage to DNA in urothelial cells. Therefore, common variation in DNA repair genes might modify bladder cancer risk. In this study, we present results from meta-analyses and pooled analyses conducted as part of the International Consortium of Bladder Cancer. We included data on 10 single nucleotide polymorphisms corresponding to seven DNA repair genes from 13 studies. Pooled analyses and meta-analyses included 5,282 cases and 5,954 controls of non-Latino white origin. We found evidence for weak but consistent associations with ERCC2 D312N [rs1799793; per-allele odds ratio (OR), 1.10; 95% confidence interval (95% CI), 1.01-1.19; P = 0.021], NBN E185Q (rs1805794; per-allele OR, 1.09; 95% CI, 1.01-1.18; P = 0.028), and XPC A499V (rs2228000; per-allele OR, 1.10; 95% CI, 1.00-1.21; P = 0.044). The association with NBN E185Q was limited to ever smokers (interaction P = 0.002) and was strongest for the highest levels of smoking dose and smoking duration. Overall, our study provides the strongest evidence to date for a role of common variants in DNA repair genes in bladder carcinogenesis.
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA. stern_m@ccnt.usc.edu
authors.forename: Mariana C
authors.initials: MC
authors.lastname: Stern
authors.forename: Jie
authors.initials: J
authors.lastname: Lin
authors.forename: Jonine D
authors.initials: JD
authors.lastname: Figueroa
authors.forename: Karl T
authors.initials: KT
authors.lastname: Kelsey
authors.forename: Anne E
authors.initials: AE
authors.lastname: Kiltie
authors.forename: Jian-Min
authors.initials: JM
authors.lastname: Yuan
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Matullo
authors.forename: Tony
authors.initials: T
authors.lastname: Fletcher
authors.forename: Simone
authors.initials: S
authors.lastname: Benhamou
authors.forename: Jack A
authors.initials: JA
authors.lastname: Taylor
authors.forename: Donatella
authors.initials: D
authors.lastname: Placidi
authors.forename: Zuo-Feng
authors.initials: ZF
authors.lastname: Zhang
authors.forename: Gunnar
authors.initials: G
authors.lastname: Steineck
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Rothman
authors.forename: Manolis
authors.initials: M
authors.lastname: Kogevinas
authors.forename: Debra
authors.initials: D
authors.lastname: Silverman
authors.forename: Nuria
authors.initials: N
authors.lastname: Malats
authors.forename: Stephen
authors.initials: S
authors.lastname: Chanock
authors.forename: Xifeng
authors.initials: X
authors.lastname: Wu
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Karagas
authors.forename: Angeline S
authors.initials: AS
authors.lastname: Andrew
authors.forename: Heather H
authors.initials: HH
authors.lastname: Nelson
authors.forename: D Timothy
authors.initials: DT
authors.lastname: Bishop
authors.forename: Sei Chung
authors.initials: SC
authors.lastname: Sak
authors.forename: Ananya
authors.initials: A
authors.lastname: Choudhury
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Barrett
authors.forename: Faye
authors.initials: F
authors.lastname: Elliot
authors.forename: Román
authors.initials: R
authors.lastname: Corral
authors.forename: Amit D
authors.initials: AD
authors.lastname: Joshi
authors.forename: Manuela
authors.initials: M
authors.lastname: Gago-Dominguez
authors.forename: Victoria K
authors.initials: VK
authors.lastname: Cortessis
authors.forename: Yong-Bing
authors.initials: YB
authors.lastname: Xiang
authors.forename: Yu-Tang
authors.initials: YT
authors.lastname: Gao
authors.forename: Paolo
authors.initials: P
authors.lastname: Vineis
authors.forename: Carlotta
authors.initials: C
authors.lastname: Sacerdote
authors.forename: Simonetta
authors.initials: S
authors.lastname: Guarrera
authors.forename: Silvia
authors.initials: S
authors.lastname: Polidoro
authors.forename: Alessandra
authors.initials: A
authors.lastname: Allione
authors.forename: Eugen
authors.initials: E
authors.lastname: Gurzau
authors.forename: Kvetoslava
authors.initials: K
authors.lastname: Koppova
authors.forename: Rajiv
authors.initials: R
authors.lastname: Kumar
authors.forename: Peter
authors.initials: P
authors.lastname: Rudnai
authors.forename: Stefano
authors.initials: S
authors.lastname: Porru
authors.forename: Angela
authors.initials: A
authors.lastname: Carta
authors.forename: Marcello
authors.initials: M
authors.lastname: Campagna
authors.forename: Cecilia
authors.initials: C
authors.lastname: Arici
authors.forename: Sung Shim Lani
authors.initials: SS
authors.lastname: Park
authors.forename: Montserrat
authors.initials: M
authors.lastname: Garcia-Closas
mesh_terms: D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D044469:Racial Groups; D012306:Risk; D012307:Risk Factors; D012907:Smoking / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C086984:XPC protein, human; D051759:Xeroderma Pigmentosum Group D Protein
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