Simple SummaryIt is widely accepted that long term mental stress increases the risk of cancer. However, it has been impossible to show this conclusively in any species due to the complexities of genetic variation and the difficulty of inducing or measuring levels of psychological stress. Here, we report evidence that heritable canine temperament that increases psychological stress in dogs is somehow linked to overall risk of multiple cancer types. We propose that studying this link in dogs would result in a new understanding of the relationship between psychological stress and risk of cancer and lead to new preventive and therapeutic veterinary medicine advances that could be tested in clinical trials in pet dogs.AbstractAlthough there is evidence that psychological stress may be associated with increased cancer risk, the effect of stress on cancer risk is difficult to study, both in humans, due to socioeconomic factors, and in animal models, due to questionable biological relevance. Here, we test whether heritable canine temperament that increases psychological stress is associated with cancer risk. The study data are breed-specific averages of incidences of multiple cancer types and of temperament classes. The latter are derived from a latent class analysis of behavioral questionnaires completed by owners (C-BARQ). We thus classified the dogs according to whether they are calm vs. reactive within and across breeds. Using meta-analysis approaches, we modeled the risk of multiple cancer types in calm vs. reactive dogs. We adjusted for breed averages of body mass and lifespan, which are common confounders that impact cancer. Our study confirms that body size has a significant effect of on risk of multiple types of cancers in dogs and shows for the first time that temperament also has a moderate effect. These findings suggest dog models of heritable psychological stress are suitable for molecular epidemiological and translational studies on its effects on cancer risk.