Companion Animals as Sentinels
for Predicting Environmental
Exposure Effects on Aging and
Cancer Susceptibility in Humans
__________
Ruth Cooper, Carol Berkower, and
Sharyl Nass, Rapporteurs
National Cancer Policy Forum
Forum on Aging, Disability, and Independence
Board on Health Care Services
Health and Medicine Division
Standing Committee on the Use of
Emerging Science for
Environmental Health Decisions
Division on Earth and Life Studies
Proceedings of a Workshop
THE NATIONAL ACADEMIES PRESS 500 Fifth Street, NW Washington, DC 20001
This activity was supported by the American Kennel Club Canine Health Foundation; Animal Cancer Foundation; College of Veterinary Medicine & Biomedical Science at Texas A&M University; Environmental Protection Agency, Contract No. 68HERC19D0011 (Task Order No. 68HERC22F0077); Flint Animal Cancer Center, Colorado State University; Morris Animal Foundation; National Cancer Institute, Contract No. HHSN263201800029I (Task Order No. HHSN26300008); National Institute of Environmental Health Sciences, Contract No. HHSN263201800029I (Task Order No. 75N98020F0018); National Institute on Aging/National Institutes of Health, Contract No. HHSN2632018000029I (Task Order 75N98019F00848); Nicholas School of the Environment; North Carolina State University College of Veterinary Medicine; and University of Colorado Cancer Center.
International Standard Book Number-13: 978-0-309-68794-2
International Standard Book Number-10: 0-309-68794-2
Digital Object Identifier: https://doi.org/10.17226/26547
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Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2022. Companion animals as sentinels for predicting environmental exposure effects on aging and cancer susceptibility in humans: Proceedings of a workshop. Washington, DC: The National Academies Press. https://doi.org/10.17226/26547.
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PLANNING COMMITTEE ON THE ROLE OF COMPANION ANIMALS AS SENTINELS FOR PREDICTING ENVIRONMENTAL EXPOSURE EFFECTS ON AGING AND CANCER SUSCEPTIBILITY IN HUMANS1
LINDA S. BIRNBAUM (Chair), Scientist Emeritus, National Institute of Environmental Health Sciences/National Toxicology Program; Scholar in Residence, Nicholas School of the Environment, Duke University
MATTHEW BREEN, Professor of Genomics, Oscar J. Fletcher Distinguished Professor of Comparative Oncology Genetics, Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University
MYRTLE DAVIS, Executive Director, Discovery Toxicology, Bristol Myers Squibb
NICOLE DEZIEL, Associate Professor, Yale School of Public Health, Yale Center for Perinatal, Pediatric, and Environmental Epidemiology
WILLIAM FARLAND, Professor Emeritus, Environmental and Radiological Health Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University
ROY JENSEN, Director, The University of Kansas Cancer Center, Kansas Masonic Cancer Research Institute; William R. Jewell, MD Distinguished Masonic Professor, The University of Kansas Cancer Center, The University of Kansas Medical Center
DANIEL PROMISLOW, Principal Investigator and Co-Director, Dog Aging Project; Professor, Department of Lab Medicine & Pathology and Department of Biology, University of Washington School of Medicine
WENDY SHELTON, Principal, Virtual Beast Consulting; Consultant, Colorado State University
CHERYL LYN WALKER, Alkek Presidential Chair in Environmental Health; Director, Center for Precision Environmental Health; Professor, Departments of Molecular & Cell Biology and Medicine, Baylor College of Medicine
Project Staff
RUTH COOPER, Associate Program Officer
TOCHI OGBU-MBADIUGHA, Senior Program Assistant
___________________
1 The National Academies of Sciences, Engineering, and Medicine’s planning committees are solely responsible for organizing the workshop, identifying topics, and choosing speakers. The responsibility for the published Proceedings of a Workshop rests with the workshop rapporteurs and the institution.
MARILEE SHELTON DAVENPORT, Senior Program Officer, Standing Committee on the Use of Emerging Science for Environmental Health Decisions (until March 2022)
TRACY A. LUSTIG, Senior Program Officer; Director, Forum on Aging, Disability, and Independence
SHARYL NASS, Senior Director, Board on Health Care Services; Co-Director, National Cancer Policy Forum
Reviewers
This Proceedings of a Workshop was reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise. The purpose of this independent review is to provide candid and critical comments that will assist the National Academies of Sciences, Engineering, and Medicine in making each published proceedings as sound as possible and to ensure that it meets the institutional standards for quality, objectivity, evidence, and responsiveness to the charge. The review comments and draft manuscript remain confidential to protect the integrity of the process.
We thank the following individuals for their review of this proceedings:
Although the reviewers listed above provided many constructive comments and suggestions, they were not asked to endorse the content of the proceedings nor did they see the final draft before its release. The review of this proceedings was overseen by ELI Y. ADASHI, Brown University. He was responsible for making certain that an independent examination of this proceedings was carried out in accordance with standards of the National Academies and that all review comments were carefully considered. Responsibility for the final content rests entirely with the rapporteurs and the National Academies.
We also thank staff member Alexandra Beatty for reading and providing helpful comments on this manuscript.
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Acknowledgments
The National Academies of Sciences, Engineering, and Medicine’s Board on Health Care Services wishes to express its sincere gratitude to the planning committee chair, Linda S. Birnbaum, for her valuable contributions to the development and orchestration of this workshop. The board also wishes to thank all the members of the planning committee, who collaborated to ensure a workshop replete with informative presentations and moderated rich discussions. We are also grateful for the support of our workshop sponsors, without which we could not have undertaken this project, particularly Danielle Carlin, National Institute of Environmental Health Sciences, and Rodney Page, Flint Animal Cancer Center, Colorado State University. Finally, the board wants to thank the speakers, who generously shared their expertise and their time with workshop participants. Research assistance was provided by Christopher Lao-Scott, National Academies.
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Contents
BACKGROUND ON CANCER, AGING, AND ENVIRONMENTAL EXPOSURE RESEARCH
Environmental Exposure and Cancer
Environmental Exposure, Cancer, and Aging in Companion Animals: The Companion Dog Model
Why Pet Dogs with Spontaneous Tumors are Good Models for Human Disease
How Diet Modulates the Tumor Microenvironment (TME)
Epigenetic Aging as a Target and Biomarker for Environmental Exposures
Domestic Dogs as a System for Understanding Aging and Life Span
Aging, Somatic Evolution, and Cancer—The Inexorable Link
Biomonitoring of Chemical Exposure in Companion Animals and Humans
Ongoing Canine Population Studies
Discussion: Advancing Use of Companion Dogs as Sentinels
RELEVANCE OF COMPANION ANIMAL EXPOSURES TO HUMAN CANCER AND AGING
Exposures to Air Pollution, Smoking, and Lead
Using Silicone Samplers to Assess Air Pollution in People and Pets
Cats as Sentinels for Persistent Organic Pollutants Indoors
Radon Exposures and Cancer in Pets
Heavy Metal Exposures in the Dogs of Chernobyl
Chemical Mixtures, Cancer, and Diet—The Example of Pesticides
Discussion: Relevance of Companion Animal Exposures to Humans
Comparative Oncology: How Dogs are Helping Researchers Understand and Treat Cancer
Biobanks for Companion Animal Sentinel Studies
Using Ontologies to Unify Genomics and Phenomics across Species
Discussion: Accelerating Cross-Species Comparisons
One Health Approaches in Arctic Indigenous Communities
Aligning Health Care for a Bonded Family Society
Discussion: Equity, Ethics, and Policy
IDENTIFYING RESEARCH GAPS AND SETTING A RESEARCH AGENDA: EXPLORING NEXT STEPS FOR THE PATH FORWARD
Obtaining Data on Pets and Exposures
Interdisciplinary Training of Researchers, Physicians, and Veterinarians for One Health
Translating the Science between Pets and People
Data Collection: Long-Term Investment
Data Collection: Tapping into Existing Cohorts (Short Term)
Continuing and Expanding the Conversation
Community Research—Engagement and Equity
CONCLUDING REMARKS AND POTENTIAL NEXT STEPS
C BIOGRAPHICAL SKETCHES OF PLANNING COMMITTEE MEMBERS AND WORKSHOP SPEAKERS
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Boxes, Figures, and Table
BOXES
2 Examples of NIEHS-Sponsored Sensor Research
3 The Golden Retriever Lifetime Study
5 Studies of Dogs as Sentinels for Testicular Dysgenesis Syndrome
FIGURES
2 The complexities of documenting exposures
3 Dogs can serve as a useful model in comparative oncology
4 The remarkable similarity in cancers that develop in humans and dogs
5 The nonlinear relationship between dog age and human age
7 The exposome: Implications for examining environmental health disparities
9 Approaches to exposure science at the NIEHS
11 The Hallmark Framework of cancer progression
12 Comparative molecular features of canine and human osteosarcomas
13 Development of species-agnostic ontologies to classify phenotypes across species
14 Integration of exposure event modeling with the Monarch Knowledge Graph
TABLE
Acronyms and Abbreviations
AAVSB | American Association of Veterinary State Boards |
ACVO | American College of Veterinary Ophthalmologists |
AD | Alzheimer’s disease |
AI | artificial intelligence |
AIDS | acquired immunodeficiency syndrome |
AKC | American Kennel Club |
AML | acute myeloid leukemia |
ATSDR | Agency for Toxic Substances and Disease Registry |
AVCC | Access to Veterinary Care Coalition |
AVMA | American Veterinary Medical Association |
BMI | body mass index |
CA | conformity assessment |
C-BARQ | Canine Behavioral Assessment & Research Questionnaire |
CBPR | community-based participatory research |
CDC | Centers for Disease Control and Prevention |
CE | continuing education |
CHIC | Canine Health Information Center |
CKD | chronic kidney disease |
CLL | chronic lymphocytic leukemia |
CML | chronic myeloid leukemia |
CO | carbon monoxide |
COHA | Clinical and Translational Science Award One Health Alliance |
COTC | (NCI) Comparative Oncology Trials Consortium |
CRC | colorectal cancer |
CRDC | Cancer Research Data Commons |
CREID | Centers for Research in Emerging Infectious Diseases |
CTL | cytotoxic T lymphocyte |
CTSA | clinical and translational science awards |
DAP | Dog Aging Project |
DDT | dichloro-diphenyl-trichloroethane |
DEHP | di(2-ethylhexyl)phthalate |
DEMS | Diesel Exhaust in Miners Study |
DOHAD | Developmental Origins of Health and Disease |
EMR | electronic medical record |
EMT | epithelial mesenchymal transition |
EPA | Environmental Protection Agency |
ER+ | estrogen-receptor-positive |
EWAS | exposome-wide association study |
FDA | Food and Drug Administration |
FH | feline hyperthyroidism |
fMRI | functional magnetic resonance imaging |
GC | gas chromatography |
GIS | geographic information systems |
GO | Gene Ontology |
GRLS | Golden Retriever Lifetime Study |
GXE | gene by environment |
HHEAR | Human Health Exposure Analysis Resource |
HRMS | high-resolution mass spectrometry |
IACUC | Institutional Animal Care and Use Committee |
IARC | World Health Organization International Agency for Research on Cancer |
ICDC | Integrated Canine Data Commons |
ICP-MS | inductively coupled plasma mass spectroscopy |
IGF | insulin-like growth factor |
ISBER | International Society for Biological and Environmental Repositories |
MESA | Multi-Ethnic Study of Atherosclerosis |
MET | mesenchymal to epithelial transition |
MHC | major histocompatibility complex |
ML | machine learning |
MOU | memorandum of understanding |
MS | mass spectrometry |
MWAS | metabolome-wide association study |
NASEM | National Academies of Sciences, Engineering, and Medicine |
NCI | National Cancer Institute |
NGO | nongovernmental organization |
NHANES | National Health and Nutrition Examination Survey |
NIA | National Institute on Aging |
NIEHS | National Institute of Environmental Health Sciences |
NIH | National Institutes of Health |
NIST | National Institutes of Standards and Technology |
NSRL | no-significant-risk level |
NTP | National Toxicology Program |
OFA | Orthopedic Foundation for Animals |
PATO | Phenotype and Trait Ontology |
PBDE | polybrominated diphenyl ether |
PBMC | peripheral blood mononuclear cell |
PBPK | physiologically based pharmacokinetics |
PCB | polychlorinated biphenyl |
PDMS | polydimethylsiloxane |
PEGS | Personalized Environment and Genes Study (NIEHS) |
PET/CT | positron emission tomography–computed tomography |
PFAS | poly- and perfluoroalkyl substances |
PFHxS | perfluorohexane sulfonate |
PFOA | perfluorooctanoic acid |
PFOS | perfluorooctane sulfonic acid |
PHD3 | prolyl-hydroxylase 3 |
PI | principal investigator |
PK | pharmacokinetics |
POC | point of care device |
POP | persistent organic pollutant |
PPN | primary pulmonary neoplasia |
RACE | Registry of Approved Continuing Education |
SARS | severe acute respiratory syndrome |
SES | socioeconomic status |
SHS | secondhand smoke |
SNP | single nucleotide polymorphism |
STR | short tandem repeat |
TBT | tributyltin |
TDCIPP | tris(1,3-dichloroisopropyl)phosphate |
TDS | testicular dysgenesis syndrome |
TME | tumor microenvironment |
TRI | Toxics Release Inventory program |
TRIAD | Test of Rapamycin in Aging Dogs clinical trial |
TVMDL | Texas A&M Veterinary Medical Diagnostic Laboratory |
UFP | ultrafine particle |
VOC | volatile organic compound |
WHICAP | Washington Heights/Inwood Columbia Aging Project |
WHO | World Health Organization |