Maine Cancer Foundation

Introduction: Disinfection by-products (DBPs) have been linked to bladder cancer, with brominated species hypothesized to confer greater risk. The potential modifying role of genetic susceptibility is not well-studied. One study suggested an interaction between total trihalomethanes (THM), a DBP surrogate, and polymorphisms in glutathione S-transferase (GST) genes on bladder cancer risk; some enzymes in these metabolic pathways activate brominated THMs to mutagens (GSTT1) or catalyze the oxygenation of some haloacids (GSTZ1). In addition, bladder cancer genome wide association studies (GWAS) have identified several risk loci that have not been evaluated for interaction with these putative bladder carcinogens. Methods: In a New England population-based case-control study, we estimated exposure to total, chlorinated, and brominated THMs from ingestion and showering/bathing based on residential histories, and historical information from public water utilities. We examined the effects of THMs by polymorphisms in candidate genes, and by bladder cancer GWAS loci among 847 cases and 1,007 controls. Results: Although there was a modest increased risk related to showering/bathing with high brominated THM levels overall, we observed no significant interaction with GSTT1 copy number (p-interaction=0.99) or GSTZ1 SNP rs1046428 (p-interaction=0.38). We also observed no interaction between average concentration of brominated THMs and GSTT1 copy number (p-interaction=0.27) or GSTZ1 SNP rs1046428 (p-interaction=0.76). We will present results for THMs and polymorphisms in bladder cancer GWAS loci. Discussion: Previously reported gene-environment interactions for THMs require replication. Although our results do not replicate previously reported results, our power was limited by lower THM levels than the only other study to evaluate this association. In addition, this is the first study to evaluate GWAS loci in conjunction with THMs and bladder cancer risk.