Genome-wide interaction study of smoking and bladder cancer risk

Jonine D. Figueroa, Summer S. Han, Montserrat Garcia-Closas, Dalsu Baris, Eric J. Jacobs, Manolis Kogevinas, Molly Schwenn, Nuria Malats, Alison Johnson, Mark P. Purdue, Neil Caporaso, Maria Teresa Landi, Ludmila Prokunina-Olsson, Zhaoming Wang, Amy Hutchinson, Laurie Burdette, William Wheeler, Paolo Vineis, Afshan Siddiq, Victoria K. CortessisCharles Kooperberg, Olivier Cussenot, Simone Benhamou, Jennifer Prescott, Stefano Porru, H. Bas Bueno-de-Mesquita, Dimitrios Trichopoulos, Börje Ljungberg, Françoise Clavel-Chapelon, Elisabete Weiderpass, Vittorio Krogh, Miren Dorronsoro, Ruth Travis, Anne Tjønneland, Paul Brenan, Jenny Chang-Claude, Elio Riboli, David Conti, Manuela Gago-Dominguez, Mariana C. Stern, Malcolm C. Pike, David van den Berg, Jian Min Yuan, Chancellor Hohensee, Rebecca Rodabough, Geraldine Cancel-Tassin, Morgan Roupret, Eva Comperat, Constance Chen, Immaculata de Vivo, Edward Giovannucci, David J. Hunter, Peter Kraft, Sara Lindstrom, Angela Carta, Sofia Pavanello, Cecilia Arici, Giuseppe Mastrangelo, Margaret R. Karagas, Alan Schned, Karla R. Armenti, G. M. Monawar Hosain, Chris A. Haiman, Joseph F. Fraumeni, Stephen J. Chanock, Nilanjan Chatterjee, Nathaniel Rothman, Debra T. Silverman

Research output: Contribution to journalArticlepeer-review


Bladder cancer is a complex disease with known environmental and genetic risk factors. We performed a genome-wide interaction study of smoking and bladder cancer risk based on primary scan data from 3,002 cases and 4,411 controls from the NCI Bladder Cancer Genome-Wide Association Study (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 were evaluated further in an independent dataset of 2,422 bladder cancer cases and 5,751 controls. We identified 10 SNPs that showed association in a consistent manner with the initial data set and in the combined data set, 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 OR=1.34, 95% CI=1.20-1.50, P-value=5.18x10-7); 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=6.35x10-7). 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, while 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.

Original languageEnglish
Issue number8
Publication statusPublished - 2014


  • Bladder cancer
  • Gene-environment interaction

ASJC Scopus subject areas

  • Cancer Research
  • Medicine(all)


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