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Bladder Cancer

Kidney Disease

Bladder cancer

Cancer is estimated to affect one out of every four dogs, regardless of breed, making it the most common cause of disease related death in the dog. Transitional cell carcinoma (TCC) of the bladder is the most common tumor of the urinary bladder affecting as many as 20,000 dogs each year. As with many diseases, some breeds are more susceptible to developing TCC than others. Scottish and West Highland White Terriers are the 2 most susceptible. Shetland Sheepdogs are the 3rd most likely breed as they are five times more likely to develop TCC than other dogs. This increase in risk suggests that there is an inherited component that predisposes some dogs to TCC.

There are 2 active studies in which Shetland Sheepdog owners can participate.

Study 1: Ostrander Laboratory at the National Human Genome Research Institute at NIH

In early 2006, the Ostrander Laboratory at the National Human Genome Research Institute at NIH in collaboration with the Purdue Comparative Oncology Program at Purdue University and the Department of Small Animal Clinical Sciences at Michigan State University began a study on the genetic susceptibility to transitional cell carcinoma (TCC) of the urinary bladder in West Highland White and Scottish Terriers. In 2008, at the request of the ASSA, Shetland Sheepdogs were included in the study. Of key interest was the determination of the variant responsible for this disease in the Sheltie and whether different breeds had the same or similar genetic variants responsible for susceptibility to TCC.

In 2015, year the researchers identified a mutation in the BRAF gene present in 85% of TCC tumors, including 100% of the Shetland sheepdog tumors tested. This exact mutation has been found in many human cancers including melanomas, colon cancer, thyroid cancers, leukemias, and even human bladder cancers.

They found that the BRAF mutation can be identified in urine from affected dogs and have published their findings (Decker, 2015). This has led to a urine-based diagnostic/screening test for TCC (Sentinel Biomedical). It is predicted that early diagnosis and early treatment will improve the prognosis for all dogs with TCC.

Their genome wide association studies have identified two distinct regions of the genome that appear to hold cancer-causing mutations in breeds at risk for TCC. One of these regions is specific to the Shetland sheepdog. They have sequenced the complete genome of a Sheltie, a Westie, and a Scottie that were diagnosed with TCC of the bladder which allowing them to look for mutations that could cause the disease.

“The Ostrander Laboratory would like to express our gratitude to the American Shetland Sheepdog Association and all Sheltie owners for their great response to our numerous requests for blood samples. We have received samples from over 200 Shelties, nearly half of which have been diagnosed with TCC of the bladder.”

This study is ongoing and more participants are needed. Also, if you have entered your dog into the study, updated health information is requested. See information about the findings of this study and how to participate.

References:
Decker B, Parker HG, Dhawan D, et al. Homologous Mutation to Human BRAF V600E Is Common in Naturally Occurring Canine Bladder Cancer—Evidence for a Relevant Model System and Urine-Based Diagnostic Test. Mol Cancer Res; 6:993-1002, 2015.
http://mcr.aacrjournals.org/content/13/6/993.long

Conclusions:
This study demonstrates the activating BRAF mutation (V600E), which is found in multiple human cancers, is a driver of canine InvTCC, and highlights a urine-based test for quick diagnosis.

Parker HG, Dhawan D, Harris AC, Ramos-Vara JA, Davis BW, Knapp DW, Ostrander EA. RNAseq expression patterns of canine invasive urothelial carcinoma reveal two distinct tumor clusters and shared regions of dysregulation with human bladder tumors. BMC Cancer. 2020 Mar 24;20(1):251. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7092566/

Sentinel Biomedical CADETSM BRAF Mutation Detection Screening Assay for Early Detection of Canine TCC, www.sentinelbiomedical.com/store/


Study 2:

Early detection of canine bladder cancer (UC/TCC) and treatment with a dietary supplement. NC State University.

This research consists of 3 studies as noted below:

  1. Early Detection of Bladder Cancer is a study to show whether a genetic signature of UC/TCC detected in the urine of apparently healthy dogs can be used to diagnose bladder cancer earlier. We hope to diagnose this cancer before a dog develops clinical signs, which include bloody urine, straining to urinate, accidents in the house, and increased urgency.

Inclusion criteria: For this study, NC State is seeking healthy male and female dogs, age 6 years and older from seven breeds at elevated risk for bladder cancer. These breeds are Shetland sheepdog, American Eskimo dog, Beagle, Parson terrier, Russel terrier, Scottish terrier, and West Highland white terrier.

  1. Early Treatment of Bladder Cancer with a Dietary Supplement is a study to evaluate the impact of a nutritional supplement on time to progression to clinical signs in dogs that have a low level BRAF mutation detected in their urine.

Inclusion criteria: For this study, NC State is seeking male and female dogs of any age or breed that have a urinary BRAF mutation below 5% fractional abundance, but are NOT showing major clinical signs associated with UC/TCC and are NOT being treated for the cancer with anything other than an NSAID.

  1. Treatment of Later Stage Bladder cancer with a Dietary Supplement is a study to evaluate the impact of a dietary supplement on progression of bladder cancer. This supplement is added to standard of care chemotherapy (mitoxantrone and NSAID) for dogs with a current diagnosis of canine UC/TCC.

Inclusion criteria: For this study, NC State is seeking male and female dogs, of any age or breed that has recently been diagnosed with UC/TCC in the past month. In addition, the dog must have a measurable mass in the bladder, and the owner and veterinarian have decided to proceed with chemotherapy treatment (mitoxantrone and NSAID therapy).

If you would like to participate, please complete the following questionnaire.

https://csc-rc.cvm.ncsu.edu/surveys/index.php?s=MP3NEW48P3 .

Please contact us at UCClinicalTrials@ncsu.edu  with any questions.


Study 3: Bladder Carcinogen Exposures in Pet Dogs

Breed(s): -All Dogs

Study Location: University of Wisconsin, Madison

AKC Canine Health Foundation-funded Grant: 02780

Bladder cancer in dogs can lead to blood in the urine, pain on urination, and urinary blockage. The underlying causes in dogs are not well understood. The aim of this study is to determine whether urinary exposure to certain environmental chemicals contributes to bladder cancer risk in the dog.

The results of this study may help us understand what causes bladder cancer in some dogs, and whether owners of these dogs share exposure to certain chemicals in the environment. Our goal is to find better ways to prevent bladder cancer in dogs and people.

Participation Requirements:

Any dog diagnosed with bladder cancer (transitional cell carcinoma of the bladder or urethra), confirmed by tumor biopsy, genetic (BRAF) test, or examination of urinary cells, or any dog that is identified as an unaffected matched control.

Samples can be mailed.

Owner's Responsibilities:

Collect a voided 25 mL urine sample (about 2 tablespoons) from your dog using a kit that we provide. Some dogs will have a brief ultrasound exam of their bladder. We will also ask you to fill out a questionnaire about your dog’s lifestyle. Your dog will not be given any medications or undergo any other procedures related to the study.

Contact Information:

Name: Dr. Lauren Trepanier

Email: lauren.trepanier@wisc.edu

https://www.akcchf.org/research/participate-in-research/Environmental-risk-for-bladder-cancer-in-dogs.html

Kidney

Characterization of Kidney Disease in Shetland Sheepdogs

Do you own a Shetland Sheepdog that has been diagnosed with kidney disease or is related to one with kidney disease? The American Shetland Sheepdog Association and its charitable Foundation are sponsoring a study which might help determine if there is an inherited link to kidney disease in Shetland Sheepdogs.

How you can help

PHASE 1- Collection of Historical Data

1) Provide a complete pedigree of your pet, which includes identification of any relative with a diagnosis of kidney disease.

2) Share all medical records from those individuals diagnosed with kidney disease.

3) Provide access to any kidney tissue and/or laboratory values (e.g., bloodwork) which might have been

previously tested.

PHASE 2- Sample Collection from Pedigreed Families where Kidney Disease is Prevalent (Concurrent with Phase 1)

1) Kidney samples via biopsy or autopsy (dogs with kidney disease)

If your veterinarian recommends performing a kidney biopsy to determine the cause of your Sheltie’s

kidney disease, or if your dog has a diagnosis of kidney disease and is euthanized for any reason, kidney

samples can be submitted to the International Veterinary Renal Pathology Service (IVRPS) at the Ohio State University for evaluation. Biopsy samples should be collected early in the disease process to provide the best interpretation and guidance for treatment of the disease. A particularly good opportunity for collection of a kidney biopsy is at the time of spay. *  Monetary support for the cost of kidney biopsies may be available from the ASSA Foundation (see below).

2) Blood and urine (dogs with kidney disease or related unaffected dogs)

If kidney tissue is provided, blood and urine should be submitted concurrently for additional analyses

and isolation of DNA.  DNA would be used to search for causative gene(s) and ultimately development of a DNA test if a hereditary cause is found.  If kidney tissue is not provided, then blood and urine can be submitted for evaluation, which can help determine the extent to which your dog’s pedigree is affected.  Evaluations of all submitted samples will be performed at no cost to the owners and all results will be provided through their veterinarians.

*The owner’s veterinarian should obtain a free biopsy collection kit prior to the biopsy procedure as specialized tissue fixatives are needed.

For more information, please contact:

Dr. Mary Nabity Dr. Jessica Hokamp
IVRPS IVRPS
979-845-9172 614-688-3159

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Or send an email to: OSUVET.RenalPath@osu.edu, attention: Dr. Jessica Hokamp

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Monetary support for the cost of kidney biopsies from the ASSA Foundation

The determination of whether or not an inherited kidney disease process is likely in the Shetland Sheepdog will depend upon the analysis of kidney tissue obtained from as many affected dogs as possible.  Kidney biopsies can be helpful to determine diagnosis and guide treatment in dogs with kidney disease, as we currently lack non-invasive diagnostic tests to accurately identify most types of kidney disease. Kidney samples obtained early in the disease process are more likely to yield helpful information than that obtained late in the process when much of the tissue has been scarred.  However, tissue obtained shortly after death will still be useful and when possible, biopsy collection kits should be requested in advance.

When biopsies are considered diagnostically appropriate for an affected dog based on evaluation by a veterinarian, the cost may be partially subsidized by the ASSA Foundation.  Up to $500 each for the first 10 Shelties biopsied has been reserved for that purpose*.  Applications for subsidies must be approved by either Dr. Nabity or Dr. Hokamp prior to collection of tissue.  Because the cost of obtaining kidney tissue in a live dog is greater than that obtained after death, subsidy funds are reserved for tissue obtained from live dogs.

Procedure:

  1. The dog’s veterinarian or owner must contact either Dr. Nabity or Dr. Hokamp to determine if the biopsy procedure would be eligible for subsidy and to arrange for delivery of a kit to the veterinary clinic if the biopsy is intended to proceed (regardless of subsidy eligibility).
  2. If eligible, a form will be sent to the veterinarian to complete and return with the biopsy sample.
  3. After the biopsy sample, blood and urine have been received by the laboratory, the completed form will be sent to the ASSA Foundation Treasurer who will issue a check for up to $500 to the veterinarian. Because of IRS rules, the Foundation cannot issue checks directly to the owner.

*Kidney biopsies from many more affected Shelties will be needed for evaluation of kidney disease in this breed.  Funds for additional subsidies may or may not be available.

Approval will be based on the following:

  • Purebred Shetland Sheepdogs.
  • Pedigrees and medical records have been received by the researchers.
  • Blood for DNA, serum, and urine is intended to be collected and sent with the kidney biopsy.