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/
The NC State University College of Veterinary Medicine is currently recruiting dogs for these clinical studies:
1. Early Detection of Canine Bladder Cancer – this study is screening urine samples from clinically healthy dogs at increased risk of bladder cancer, to determine if they test positive for a genetic marker of the disease (a specific mutation in the dog BRAF gene). The goal is to determine whether this BRAF Mutation Detection test can identify dogs that have bladder cancer BEFORE they develop clinical signs (such as inappropriate urination, straining to urinate, blood in the urine).
Inclusion criteria: Clinically healthy male or female dogs aged six years or older from one of these breeds (American Eskimo Dog, Beagle, Russell Terrier, Parson Russell Terrier, Scottish Terrier, Shetland Sheepdog, West Highland White Terrier, Wire Fox Terrier).
2. Delaying Clinical Signs of Canine Bladder Cancer with a Dietary Supplement – this study is investigating whether a nutritional supplement DELAYS the onset of clinical signs in dogs that test positive with the BRAF Mutation Detection Test but which do not have a detectable bladder mass.
Inclusion criteria: These dogs will be recruited from the Early Detection Study described above.
3.Treatment of Canine Bladder Cancer with a Dietary Supplement – this study is investigating whether a dietary supplement slows the progression of canine bladder cancer in dogs with confirmed disease, when combined with standard of care treatment.
Inclusion criteria: Dogs of any age, sex or breed that have been diagnosed with bladder cancer within the past three months, and which have not received any cytotoxic chemotherapy (such as mitoxantrone, vinblastine). Treatment with a non-steroidal anti-inflammatory drug (NSAID) is acceptable).
In addition to the dietary supplement, enrolled dogs may be eligible for clinical evaluation for the presence of bladder cancer (typically including abdominal ultrasound), standard of care treatment (which may include chemotherapy) and periodic BRAF Mutation Detection testing, all at NO COST to the owner.
Please complete the following questionnaire to determine if your dog is eligible.
Contact UCClinicalTrials@ncsu.edu with any questions.
Links to the ongoing studies:
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.
Study update: As of February, 2023, recruitment for this study has just been completed. Thirty-nine dogs with bladder cancer and 39 matched control dogs have been enrolled. Two affected Shelties along with unaffected controls are included. They expect to receive results from the urine samples this spring. Study results should be published in the future.
Name: Dr. Lauren Trepanier