Whole Blood <scp>DNA</scp> Damage Precedes a Diagnosis of Canine Multicentric Lymphoma and Correlates With Environmental Chemical Exposures

Canine multicentric lymphoma is a common cancer in dogs without evidence-based prevention measures. While breed accounts for part of lymphoma risk, environmental exposures might also contribute. Human non-Hodgkin lymphoma (NHL), which resembles canine lymphoma, is associated with exposures to volatile organic compounds (VOCs) and herbicides. Pet dogs are commonly exposed to these genotoxic chemicals, but it is unknown whether such exposures are associated with in vivo DNA damage as a potential contributor to lymphoma in dogs or whether early DNA damage can be detected before lymphoma diagnosis. The aims of this study were to determine whether DNA strand breaks or oxidised DNA residues precede a diagnosis of canine lymphoma and to assess whether DNA damage events correlate with estimated systemic exposures to the VOCs benzene, xylene and 1,3-butadiene or the herbicides 2,4-D and glyphosate. In a nested case-control study within the Golden Retriever Lifetime Study, we found increased DNA strand breaks in dogs with lymphoma compared to controls at the time of diagnosis (p = 0.004). We also found higher oxidised DNA residues both at the time of diagnosis (p = 0.02) and in the year prior to diagnosis (p = 0.03). DNA strand breaks across all dogs and time points were positively correlated with estimated aggregate blood VOC exposures and estimated plasma 2,4-D and glyphosate concentrations. These data indicate that detectable oxidative DNA damage may precede a diagnosis of canine lymphoma and support the hypothesis that VOC and herbicide exposures might contribute to DNA strand breaks in pet dogs.