Polymorphisms in DNA repair genes, smoking, and bladder cancer risk: findings from the international consortium of bladder cancer.
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.
Stern
Mariana C
MC
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
Lin
Jie
J
Figueroa
Jonine D
JD
Kelsey
Karl T
KT
Kiltie
Anne E
AE
Yuan
Jian-Min
JM
Matullo
Giuseppe
G
Fletcher
Tony
T
Benhamou
Simone
S
Taylor
Jack A
JA
Placidi
Donatella
D
Zhang
Zuo-Feng
ZF
Steineck
Gunnar
G
Rothman
Nathaniel
N
Kogevinas
Manolis
M
Silverman
Debra
D
Malats
Nuria
N
Chanock
Stephen
S
Wu
Xifeng
X
Karagas
Margaret R
MR
Andrew
Angeline S
AS
Nelson
Heather H
HH
Bishop
D Timothy
DT
Sak
Sei Chung
SC
Choudhury
Ananya
A
Barrett
Jennifer H
JH
Elliot
Faye
F
Corral
Román
R
Joshi
Amit D
AD
Gago-Dominguez
Manuela
M
Cortessis
Victoria K
VK
Xiang
Yong-Bing
YB
Gao
Yu-Tang
YT
Vineis
Paolo
P
Sacerdote
Carlotta
C
Guarrera
Simonetta
S
Polidoro
Silvia
S
Allione
Alessandra
A
Gurzau
Eugen
E
Koppova
Kvetoslava
K
Kumar
Rajiv
R
Rudnai
Peter
P
Porru
Stefano
S
Carta
Angela
A
Campagna
Marcello
M
Arici
Cecilia
C
Park
Sung Shim Lani
SS
Garcia-Closas
Montserrat
M
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
D004268:DNA-Binding Proteins; C086984:XPC protein, human; D051759:Xeroderma Pigmentosum Group D Protein
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