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.
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.
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/
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:
- 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.
- 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.
- 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.
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.
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.
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.
Name: Dr. Lauren Trepanier