Περίληψη:
Bladder cancer is a complex disease with known environmental and genetic
risk factors. We performed a genome-wide interaction study (GWAS) of
smoking and bladder cancer risk based on primary scan data from 3002
cases and 4411 controls from the National Cancer Institute Bladder
Cancer GWAS. Alternative methods were used to evaluate both additive and
multiplicative interactions between individual single nucleotide
polymorphisms (SNPs) and smoking exposure. SNPs with interaction P
values < 5 x 10(-5) were evaluated further in an independent dataset of
2422 bladder cancer cases and 5751 controls. We identified 10 SNPs that
showed association in a consistent manner with the initial dataset and
in the combined dataset, providing evidence of interaction with tobacco
use. Further, two of these novel SNPs showed strong evidence of
association with bladder cancer in tobacco use subgroups that approached
genome-wide significance. Specifically, rs1711973 (FOXF2) on 6p25.3 was
a susceptibility SNP for never smokers [combined odds ratio (OR) =
1.34, 95% confidence interval (CI) = 1.20-1.50, P value = 5.18 x
10(-7)]; and rs12216499 (RSPH3-TAGAP-EZR) on 6q25.3 was a susceptibility
SNP for ever smokers (combined OR = 0.75, 95% CI = 0.67-0.84, P value =
6.35 x 10-7). In our analysis of smoking and bladder cancer, the tests
for multiplicative interaction seemed to more commonly identify
susceptibility loci with associations in never smokers, whereas the
additive interaction analysis identified more loci with associations
among smokers-including the known smoking and NAT2 acetylation
interaction. Our findings provide additional evidence of
gene-environment interactions for tobacco and bladder cancer.
Συγγραφείς:
Figueroa, Jonine D.
Han, Summer S.
Garcia-Closas, Montserrat and
Baris, Dalsu
Jacobs, Eric J.
Kogevinas, Manolis
Schwenn,
Molly
Malats, Nuria
Johnson, Alison
Purdue, Mark P. and
Caporaso, Neil
Landi, Maria Teresa
Prokunina-Olsson, Ludmila and
Wang, Zhaoming
Hutchinson, Amy
Burdette, Laurie
Wheeler,
William
Vineis, Paolo
Siddiq, Afshan
Cortessis, Victoria K.
and Kooperberg, Charles
Cussenot, Olivier
Benhamou, Simone and
Prescott, Jennifer
Porru, Stefano
Bueno-de-Mesquita, H. Bas and
Trichopoulos, Dimitrios
Ljungberg, Boerje
Clavel-Chapelon,
Franoise
Weiderpass, Elisabete
Krogh, Vittorio
Dorronsoro,
Miren
Travis, Ruth
Tjonneland, Anne
Brenan, Paul and
Chang-Claude, Jenny
Riboli, Elio
Conti, David and
Gago-Dominguez, Manuela
Stern, Mariana C.
Pike, Malcolm C. and
Van den Berg, David
Yuan, Jian-Min
Hohensee, Chancellor and
Rodabough, Rebecca
Cancel-Tassin, Geraldine
Roupret, Morgan and
Comperat, Eva
Chen, Constance
De Vivo, Immaculata and
Giovannucci, Edward
Hunter, David J.
Kraft, Peter
Lindstrom,
Sara
Carta, Angela
Pavanello, Sofia
Arici, Cecilia and
Mastrangelo, Giuseppe
Karagas, Margaret R.
Schned, Alan and
Armenti, Karla R.
Hosain, G. M. Monawar
Haiman, Chris A. and
Fraumeni, Jr., Joseph F.
Chanock, Stephen J.
Chatterjee,
Nilanjan
Rothman, Nathaniel
Silverman, Debra T.
