Canine Urothelial <scp>DNA</scp> Mutations Are Not Associated With Total Trihalomethanes Concentrations in Municipal Drinking Water

Contaminants in municipal drinking water, specifically total trihalomethanes (TTHMs), are mutagenic. Exposures to TTHMs have been associated with urothelial carcinoma (UC) in both people and dogs. Mutations in the BRAF gene and other genomic copy number aberrations detected in voided urothelial cells with commercial CADET BRAF and BRAF-PLUS tests have also been associated with the presence of UC in dogs. However, it is not known whether these urothelial mutations can be linked to TTHM exposures in dogs. The objectives of this ecological study were to compare the incidence of detected urinary BRAF mutations or genomic copy number aberrations in dogs residing in a city with relatively high drinking water TTHMs (Las Vegas, NV) to a city with significantly lower TTHMs (Reno, NV), and to expand the study group to include BRAF and BRAF-PLUS test results and municipal drinking water TTHM concentrations by zip code across the United States. Dogs living in Las Vegas had a higher relative risk of urothelial mutations compared to dogs living in Reno (RR 2.52; 95% CI, 1.77-3.38; p < 0.0001). However, this risk could not be attributed to higher municipal drinking water TTHMs. Across the United States, the population-adjusted incidence of urothelial mutations in voided urine was not associated with municipal water TTHMs, but was instead associated in cross-sectional analyses with age, neutered status, higher regional test submission rates and previously reported high-risk breeds for UC (Scottish terriers, West Highland white terriers, Shetland sheepdogs, beagles and wirehaired fox terriers). The higher RR for a positive BRAF or BRAF-PLUS test in Las Vegas versus Reno could be solely due to higher test submission rates (2.97 versus 0.97 per 1000 dogs) but could also reflect other environmental exposures not considered in this study.