Environmental Exposure and Aging/Cancer in Companion Animals: Research and Resource Gaps

Wendy Shelton DVM, MPH Rodney Page DVM

FACC Consultant Professor and Director FACC

• National Academies Workshops provide a venue (physical &/or virtual) to explore what is known from disparate sources, identify gaps in knowledge and support networking under “fair witness” auspices and the serious imprimatur of an illustrious body
• Historical precedent that a Workshop can generate research support/funding (2015)
• National Academies’ product is public: including complete video and transcript, published proceedings, and meeting summaries LINK : The Role of Companion Animals as Sentinels for Predicting Environmental Exposure Effects on Aging and Cancer Susceptibility in Humans A Workshop | National Academies
• PDF of proceedings available: https://NAP.edu/26547
• Sponsorship from NCI, NIA, NIEHS, EPA, Academia, Foundations
• Committee Chair: Dr. Linda Birnbaum, Director Emeritus NIEHS/NTP

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Workshop Agenda: �Are Pets Valuable as Sentinels for Human Cancer?

• History and Current State of the Science of Environmental Exposure Effects on Cancer Susceptibility – Human and Companion Animals

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• Relevance of Companion Animal Exposures to Human Cancer

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• Accelerating Cross-species Comparisons: Opportunities and Challenges in Data Sources, Collection, Storage, Modeling, and Sharing

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• Equity, Ethics, and Policy

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• Identifying Research Gaps and Setting a Research Agenda: Recommendations and Next Steps for the Path Forward

• Comparative Exposure Assessment Using Silicone Passive Samplers Indicates That Domestic Dogs Are Sentinels To Support Human Health Research.

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• Wise et al. Environmental Science & Technology 2020 54 (12), 7409-7419, DOI: 10.1021/acs.est.9b06605

Select Content of the Workshop

• WE KNOW they share exposures with humans ( Wise, Breen et al) silicone tags
• Canine genetic systems and their relevance for human cancers
• Sample collection and storage, geospatial tools
• Gaps in data collection and databases – challenges of data integration
• Ongoing longitudinal population studies (Golden Retriever Lifetime Study and Dog Aging Project)
• Toxics Exposures: VOC Exposure, Endocrine disruptors e.g, PFAS, Radon, Heavy metal, Diet, Pesticides/Herbicides, mixtures
• Ethics of companion animal studies
• All of the above in the context of Environmental Justice

A Selection of Canine Cancer Sentinel Studies Showing Positive Association�

Owner exposure to asbestos associated with mesothelioma in dogs. Glickman et al., 1983

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Exposure to topical insecticides associated with bladder cancer in dogs. Glickman et al., 1989

Dog transitional cell carcinoma associated with both insecticide and herbicide use, with an additive effect.

Glickman et al., 2004

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Passive smoking associated with lung cancer in short-nosed dogs. Reif et al., 1992

Passive smoking associated with nasal cancer in long-nosed dogs. Reif et al., 1998

Passive smoking associated with lymphoma in cats. Bertone et al. 2002

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Cases of canine malignant lymphoma (n = 491) associated with exposure to 2-4D lawn chemicals. Hayes et al.,

1991

Canine lymphoma cases (n = 608) associated with exposure to waste incinerators, polluted sites, and radioactive

waste. Pastor et al., 2009

Canine lymphoma cases (n = 263) associated with commercial lawn pesticide use. Takashima-Uebelhoer et al., 2012

Geographical variation found in incidence of golden retriever lymphoma (n = 454). Ruple et al., 2017

Gut microbiome of dogs with lymphoma (n = 12) differs from that of healthy dogs. Gavazza et al., 2018

Boxers with lymphoma (n = 63) more likely to live near a nuclear power plant, chemical suppliers, or crematorium.

Craun et al., 2020

Companion Animals as Bio-Sentinels

• Intimate Association with Humans
• Indoor contaminants > outdoor
• Exposures similar to toddlers (mouthing, crawling, surface exposures)
• Dust borne PBDE and PFAS >> toddlers than adults.
• Lifespan & Latency Contraction
• Lifespan exposure limited to one location
• Transgenerational exposure/outcome
• Longitudinal sampling
• Extensive lifestyle characterization
• Environmental Health Disparities similar to humans
• Fewer confounding risk factors

• Epigenetic similarity to human's unknown
• Does shared exposome produce similar epigenome?
• Exposure sensitivity >> human
• Outcomes not necessarily equivalent ( i.e. end organ sensitivities)
• Electronic Health Record
• Data standardization with human EHR
• Vet ICD O coding system
• Health AI/NLP integration of metadata across species – Monarch Initiative
• Canine/Feline Phenotype Ontology
• Disease Ontoloy, Exposure Ontology
• Human cohort engagement

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Positive Attributes Limitations/Gaps

Environmental Justice or “How biased is our data?”

This topic was raised by the National Academy - appropriately

The most environmentally polluted sites are often occupied by people of lower SES who also own pets

Lower SES may not have access to protective education (water, food, lawns)

In the US lower SES may not have access to human healthcare, and there is a dearth of traditional veterinary care – also historical mistrust of clinical trials

Are we sampling a limited portion or the overall population and thus creating bias?

Circumscribed geographic sites could provide accurate population numbers for both dogs and people and support strong validation for sentinel science

Pets should be part of the national census, and sampling in suspect regions may require human and animal health investments for access

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Translational Opportunities:

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• Exposure/Outcome Predictions and Mitigation
• Obesity comparisons
• Diet & lifestyle comparisons
• Owner engagement and parallel study