Genome-wide interaction study of smoking and bladder cancer risk.

Publication Type:

Journal Article

Source:

Carcinogenesis, Volume 35, Issue 8, p.1737-44 (2014)

Keywords:

2014, April 2014, Center-Authored Paper, Public Health Sciences Division, Scientific Imaging Core Facility, Shared Resources

Abstract:

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 <5x10(-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.