THE GOLDEN RETRIEVER LIFETIME STUDY · The Golden Retriever Lifetime Study _____ 13 The first pilot study nested within the Golden Retriever Lifetime Study was a collaboration between

THE GOLDEN RETRIEVER LIFETIME STUDY:5 Years of Progress in Veterinary Health and BiobankingBy Sharon Albright, DVM

2The Golden Retriever Lifetime Study ________________________________________________________________________________________________________________________________________________________________

BIOBANKING & BIOREPOSITORY

this eBook

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About Morris Animal Foundation

Established in 1948, Morris Animal Foundation is dedicated to improving

and protecting the health of animals through scientific innovation, education

and inspiration. Our investment in research has yielded life-saving vaccines,

new treatments for critical diseases, superior screening tests, and advanced

diagnostic tools. We respond to emerging animal health threats that

endanger entire species, and make new discoveries in basic animal biology

to support applied research. With every study we fund – more than 2,600 to

date – we strive to advance the science of veterinary medicine, honoring the

founding principles of Dr. Mark L. Morris Sr. to benefit animals worldwide.

Learn more at morrisanimalfoundation.org


Cancer is the leading cause of death in dogs over

the age of two, and Golden Retrievers (GRs) are

at high risk of cancer development. Morris Animal

Foundation wishes to better define the incidence

and risk factors for cancer in GRs enrolled in

this cohort and assess the risk factors for other

major medical conditions, diseases and disorders

in GRs enrolled in this cohort by conducting a

prospective lifetime cohort study.

The Golden Retriever Lifetime Study is a

prospective cohort study of approximately 3,000

GRs under the age of 2 years at enrollment with

subsequent annual health exams, laboratory

tests, questionnaire responses, and sample

collection for archival storage. Dogs will be

followed from the time of enrollment until death.

Overview of the Golden Retriever Lifetime Study

The Golden Retriever Lifetime Study is a prospective cohort study of approximately 3,000 GRs under the age of 2 years at enrollment


Goals and Objectives

The goals of the Golden Retriever Lifetime Study are to:

(1) Estimate the incidence of cancer in GRs in this cohort,

(2) Identify genetic, nutritional, lifestyle and environmental risk fac-

tors for cancer in GRs and the potential gene/environment interac-

tions of populations susceptible to specific exposures, and

(3) Characterize the epidemiology of other common diseases that

occur in GRs during the study period and investigate any associa-

tions with potential risk factors.

The core objectives of the Golden Retriever Lifetime Study

are to:

(1) Determine the incidence of four significant types of cancer

(Hemangiosarcoma, Osteosarcoma, Lymphoma and Mast Cell

Tumor) in this cohort.

(2) Identify germline genetic variants associated with common

cancers in GRs.

(3) Characterize the lifestyle, environmental and nutritional risk

factors associated with cancer development among enrolled

GRs.

(4) Establish extensive data and biological sample repositories for

future analyses of major diseases, disorders or conditions in GRs.

(5) Explore associations between genetic variations, potential risk

factors and the development of specific cancers.

(6) Estimate the incidence and risk factors for other common

health disorders in this cohort of GRs.


Principal Investigator

The principal investigator for the Golden Retriever

Lifetime Study is Rodney Page DVM MS, Director

of the Flint Animal Cancer Center at Colorado State

University. A fourth-generation Colorado native, Dr.

Page earned his veterinary degree from Colorado

State University. After completing an oncology

residency at the esteemed Animal Medical Center in

New York City, he helped establish the comparative

veterinary oncology program at North Carolina State

University’s College of Veterinary Medicine. After

spending 15 years at NC State, Dr. Page became

the founding Director of the Sprecher Institute for

Comparative Cancer Research and Chair of the

Department of Clinical Sciences in the College of

Veterinary Medicine at Cornell University. In 2010,

Dr. Page returned to the mountains of Colorado as

Director of Colorado State University’s Flint Animal

Cancer Center.

I can’t overestimate the importance of this study as a model for the way to gather important medical data that will be linked to environmental and lifestyle issues of our patients,” said Dr. Page “This project was developed based on several large-scale human studies, although answers to our questions will be answered in a fraction of the time it takes a similar human study to be completed.

”


Compliance/Endpoint Data to Date

As of December 31, 2017:

55 dogs have been withdrawn from the study

69 dogs are deceased

2,920 dogs remain in the study along with 2,697 owners and

2,001 veterinarians

84% of enrolled dogs are fully compliant with study protocol (completed

owner questionnaire, sample collection, and veterinary questionnaire for

every year).

30 diagnoses of the primary four cancers (hemangiosarcoma,

lymphoma, high grade mast cell tumor, and osteosarcoma) have been

recorded.

17 dogs have died from one of the four primary cancers being studied.


Morris Animal Foundation published the first call for pilot

study proposals using Golden Retriever Lifetime Study data

and/or biosamples in September of 2017. Proposals will

be reviewed by the principal investigator, study director,

staff scientist and members of the study’s Scientific

Steering Committee. Pilot studies demonstrating scientific

merit, relevance to the objectives of the Golden Retriever

Lifetime Study, and judicious use of the biosamples will

allow collaboration between Morris Animal Foundation and

researchers to identify priorities for further study.

First Request for Proposals for Pilot Studies


Past and Future Challenges

As with all projects, unforeseen challenges arise.

By partnering with industry leaders, the Golden

Retriever Lifetime Study team will navigate

through some difficulties associated with sample

storage, sample valuation, and planning for

bioinformatics management.

Sample Storage

Fisher Clinical Services is instrumental in

processing Golden Retriever Lifetime Study

biosamples received from veterinarians

across the contiguous United States.

Aliquoting samples and managing the

biorepository provides a unique resource to

researchers studying many aspects of canine

health.

Sample Valuation

Morris Animal Foundation is working with

industry leaders to prioritize use of biosamples

collected. Factors such as sample degradation,

relative value of samples from participants

diagnosed with cancer versus other disease

versus no disease, and economic sample

storage are all being considered.

Planning for Bioinformatics Management

With plans to collect extensive data on the

microbiome, metabolomics, proteomics,

transcriptomics, etc. from 3,000+ subjects,

bioinformatics management is an important

focus as the Golden Retriever Lifetime Study

moves through the data collection phase.


Annual Protocol

The owner completes an extensive online questionnaire regarding

familial health history (sire, dam and littermates), physical activity,

environment, and nutrition.

The dog receives a comprehensive physical examination by

the primary care veterinarian of their choice that has agreed to

participate in the study. Bio-samples are collected including whole

blood, serum, urine, feces, hair, and toenail trimmings. Part of

these samples are sent to ANTECHTM Diagnostics (a platinum

partner of the Golden Retriever Lifetime Study) for immediate

analysis which includes a cbc/chemistry, T4, heartworm antigen,

urinalysis, and fecal ova and parasite tests. The remainder of the

samples are shipped to Fisher Clinical Services biorepository for

use in current and future research.

The veterinarian completes an online questionnaire detailing the

physical examination findings as well as diagnoses, medications

and vaccines from the previous 12 months.


The dog receives a comprehensive physical examination

and tumor biopsy (whenever possible).

Tumor tissue is evaluated by a pathologist at ANTECHTM

Diagnostics for diagnosis and margin evaluation as needed.

Histopathologic diagnosis is confirmed by a veterinary

pathology resident and their mentor at Colorado State

University before tissues are stored at Fisher Clinical

Services biorepository for future research. This provides a

high level of confidence in the histopathologic diagnosis and

supports Morris Animal Foundation’s mission to educate the

next generation of scientists.

Whole blood, serum, urine, feces, hair, and toenails are also

collected at the time of cancer diagnosis. Part of these

samples are sent to Antech Diagnostics for immediate

analysis which includes a cbc/chemistry, T4, heartworm

antigen, urinalysis, and fecal ova and parasite tests. The

remainder of the samples are shipped to Fisher Clinical

Services biorepository for use in future research.

Cancer diagnosis protocol

Once malignancy is confirmed, the veterinarian completes an on-line questionnaire summarizing the diagnosis and physical examination findings from the day of diagnosis.


Biosample Management

Sample integrity is essential to the success of every biobanking project. Various types of unwanted pre-analytical variables can be introduced at numerous points in the life of a sample, beginning at the time it is collected, through transport, receiving, laboratory processing, during storage and subsequent retrieval for analysis. In order to prevent loss of integrity among samples, all parties involved in the collection and storage of biospecimens must follow certain practices. For best results, these procedures should be based on up-to-date, relevant research studies that demonstrate the most effective methods for storing specimens, as well as the maximum length of time they can be safely stored.

Biosamples available from the Golden Retriever Lifetime Study include:

i. Baseline/1st examination:- DNA - 5 x 5ug each, 3 x 50 ug each and 1 x remaining stored at -80°C and Whatman card stored at ambient temperature.- Whole blood 10 x 1 ml cryovials: stored at -80°C- Serum 10 x 1 ml cryovials: stored in LN2 tanks- Urine 5 x 1 ml cryovials: stored at -80°C- Feces ~1 gram: stored at -80°C - Hair and nail trimmings: stored at -80°C

ii. Annual examinations:- Whole blood 10 x 1 ml cryovials: stored at -80°C- Serum 10 x 1 ml cryovials: stored in LN2 tanks- Urine 5 x 1 ml cryovials: stored at -80°C- Feces ~1 gram: stored at -80°C - Hair and nail trimmings: stored at -80°C


The first pilot study nested within the Golden

Retriever Lifetime Study was a collaboration

between Morris Animal Foundation and Dr. Chris

Miller and his team at the University of Colorado,

Denver to examine the fecal microbiome of 24

dogs that submitted samples for enrollment

in the study. (Not all of these dogs completed

the requirements for enrollment in the study.)

The Miller lab is interested in understanding

community complexity at a systems level for

microbial communities relevant to the environment,

bioenergy production, and health and disease.

Microbiome Pilot


Advances in Cancer Research

Cancer remains an important cause of illness and death

in dogs. According to the Centers for Disease Control,

approximately 6 million dogs are diagnosed with cancer

each year. Several surveys, including a recent survey of

Canine Lifetime Health Project participants, reveal that

cancer is a top concern for dog owners.

The Golden Retriever Lifetime Study provides veterinary

researchers an

unprecedented opportunity to identify risk factors

for cancer development, which can lead to better

preventive strategies. However, cancer is still expected

to touch the lives of at least 60 percent of the dogs

in the study cohort. Morris Animal Foundation is

committed to collaborating with researchers to maximize

the information gained from the biosamples stored at

Fisher Clinical Services.

6 million dogs are diagnosed with cancer

each year.


Types of Studies Our Samples Can Support

In an era of “big data,” few studies in veterinary medicine will have the

amount of data collected that we anticipate with the Golden Retriever

Lifetime Study. Thousands of data points are collected each year,

from laboratory test values to behavioral assessments. All data will be

available to qualified researchers.

We anticipate that the samples could be used in a variety of ways,

including development and validation of new technologies and in studies

focusing on associations uncovered by data analysis. We’re still a long

way off from collecting all required samples, but anticipate promoting the

samples already stored, as well as informing the scientific community as

a whole about the repository of samples available.


How to Request Samples and Data

Successful completion of the Golden

Retriever Lifetime Study objectives

depends on collaboration within the

veterinary, comparative, and translational

medical communities. If you are interested

in collaborating with the Golden Retriever

Lifetime Study on data and/or biosample

research, please contact

Morris Animal Foundation at GRDogs@

caninelifetimehealth.org.


Thank You to Our Partners

Morris Animal Foundation thanks the following

partners for their support of the Golden

Retriever Lifetime Study

Founding partner – The Mark & Bette Morris

Family Foundation

Platinum partners – Blue Buffalo Foundation,

Petco, VCA Antech

Gold sponsors – Golden Retriever Foundation,

Hadley and Marion

Stuart Foundation, Zoetis

Golden champions – Mars Veterinary


Publications to Date

The Golden Retriever Lifetime Study: establishing an observational cohort

study with translational relevance for human health

Michael K. Guy, Rodney L. Page, Wayne A. Jensen, Patricia N. Olson, J.

David Haworth, Erin E. Searfoss, Diane E. Brown

Phil. Trans. R. Soc. B 2015 370 20140230; DOI: 10.1098/

rstb.2014.0230. Published 8 June 2015

Population Characteristics of Golden Retriever Lifetime Study Enrollees

Melissa Simpson, DVM, PhD; Erin Searfoss; Sharon Albright, DVM; Diane

E Brown, DVM, PhD, DACVP; Barbara Wolfe, DVM, PhD, DACZM; Nancy

Kay Clark; Susan McCann, PhD; David Haworth, DVM, PhD, DACVIM;

Mike Guy, DVM, PhD; Rod Page, DVM, MS, DACVIM

Canine Genetics and Epidemiology 2017 4:14

BSEBMAF5Y1118

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THE GOLDEN RETRIEVER LIFETIME STUDY · The Golden Retriever Lifetime Study _____ 13 The first pilot study nested within the Golden Retriever Lifetime Study was a collaboration between