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 questionnairebased 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.

Risk of bladder cancer and lymphoma in dogs is associated with pollution indices by county of residence

“…US county of residence data were available for 56 of 63 boxers with lymphoma and 84 of 89 unaffected control boxers ≥10 years old from a previous case–control study 32 . At the time of original enrolment, boxers with lymphoma resided in 41 different counties across 17 states, and unaffected control boxers resided in 78 different counties across 27 states (Table 1).…”

“…In addition, our cases and controls were not matched for age, since we deliberately chose our unaffected control groups to be at or over the median age of onset of UCC 24 or T cell lymphoma. 32 This could have created some unintended structural bias for the current analyses. time spent outdoors.…”

“…For example, for the small observed differences in NATA risk from airborne PAHs (boxer lymphoma cases, 0.1877, control boxers 0.1210) we would have needed 127 boxer dogs in each group to show this difference, if real, to be significant. In addition, our cases and controls were not matched for age, since we deliberately chose our unaffected control groups to be at or over the median age of onset of UCC 24 or T cell lymphoma 32 . This could have created some unintended structural bias for the current analyses.…”

“…Counties were also flagged as exceeding health‐based standards for water concentrations of these chemicals if averages were over Environmental Protection Agency (EPA) established compliance limits, which is 10 ppb for arsenic, 10 mg/L (ppm) for nitrate and 80 ppb for tap water total trihalomethanes (TTHMs). In addition, because dogs were reported by their owners to drink water from different sources, water exposure data were re‐analysed for the sub‐group of dogs in each case–control study whose drinking water was primarily (>50%) from municipal tap water, as opposed to well water, bottled water, filtered water or other sources 24,32 …”

“…US county of residence data were available for 56 of 63 boxers with lymphoma and 84 of 89 unaffected control boxers ≥10 years old from a previous case-control study. 32 Complete tap water arsenic data were available for 60.9% of lymphoma case counties and 50% of lymphoma control counties. From available data, boxer dogs with lymphoma did not show a difference in county tap water arsenic concentrations (median 0.000 ppb, range 0.00-2.26; n = 39) compared to control boxers (0.000 ppb, range 0.000-2.24, n = 54; p = .39), and none exceeded the EPA threshold for arsenic.…”