Genetic and environmental risk for lymphoma in boxer dogs

Abstract Background Non‐Hodgkin lymphoma in humans is associated with environmental chemical exposures, and risk is enhanced by genetic variants in glutathione S‐transferases (GST) enzymes. Objective We hypothesized that boxer dogs, a breed at risk for lymphoma, would have a higher prevalence of GST variants with predicted low activity, and greater accumulated DNA damage, compared to other breeds. We also hypothesized that lymphoma in boxers would be associated with specific environmental exposures and a higher prevalence of canine GST variants. Animals Fifty‐four healthy boxers and 56 age‐matched nonboxer controls; 63 boxers with lymphoma and 89 unaffected boxers ≥10 years old. Methods We resequenced variant loci in canine GSTT1, GSTT5, GSTM1, and GSTP1 and compared endogenous DNA damage in peripheral leukocytes of boxers and nonboxers using the comet assay. We also compared GST variants and questionnaire‐based environmental exposures in boxers with and without lymphoma. Results Endogenous DNA damage did not differ between boxers and nonboxers. Boxers with lymphoma were more likely to live within 10 miles of a nuclear power plant and within 2 miles of a chemical supplier or crematorium. Lymphoma risk was not modulated by known canine GST variants. Conclusions and Clinical Importance Proximity to nuclear power plants, chemical suppliers, and crematoria were significant risk factors for lymphoma in this population of boxers. These results support the hypothesis that aggregate exposures to environmental chemicals and industrial waste may contribute to lymphoma risk in dogs.