Genome-wide interaction study of smoking and bladder cancer risk
Figueroa, J. D.; Han, S. S.; Garcia-Closas, M.; Baris, D.; Jacobs, E. J.; Kogevinas, M.; Schwenn, M.; Malats, N.; Johnson, A.; Purdue, M. P.; Caporaso, N.; Landi, M. T.; Prokunina-Olsson, L.; Wang, Z.; Hutchinson, A.; Burdette, L.; Wheeler, W.; Vineis, P.; Siddiq, A.; Cortessis, V. K.; Kooperberg, C.; Cussenot, O.; Benhamou, S.; Prescott, J.; Porru, S.; Bueno-de-Mesquita, H. B.; Trichopoulos, D.; Ljungberg, B.; Clavel-Chapelon, F.; Weiderpass, E.; Krogh, V.; Dorronsoro, M.; Travis, R.; Tjønneland, A.; Brenan, P.; Chang-Claude, J.; Riboli, E.; Conti, D.; Gago Dominguez, Manuela; Stern, M. C.; Pike, M. C.; Van Den Berg, D.; Yuan, J. M.; Hohensee, C.; Rodabough, R.; Cancel-Tassin, G.; Roupret, M.; Comperat, E.; Chen, C.; De Vivo, I.; Giovannucci, E.; Hunter, D. J.; Kraft, P.; Lindstrom, S.; Carta, A.; Pavanello, S.; Arici, C.; Mastrangelo, G.; Karagas, M. R.; Schned, A.; Armenti, K. R.; Hosain, G. M.; Haiman, C. A.; Fraumeni, J. F.; Chanock, S. J.; Chatterjee, N.; Rothman, N.; Silverman, D. T.
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Identificadores
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Fecha de publicación
2014Título de revista
CARCINOGENESIS
Tipo de contenido
Artigo
MeSH
Adult | Biomarkers, Tumor | Case-Control Studies | Gene-Environment Interaction | Genetic Predisposition to Disease | Genome, Human | Humans | Meta-Analysis as Topic | Polymorphism, Single Nucleotide | Prognosis | Risk Factors | Smoking | Urinary Bladder NeoplasmsResumen
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.
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