Transitional Cell Carcinoma (TCC) is the most common type of bladder cancer in pet dogs and has a high rate of metastasis, often spreading to the lungs or liver. Treatment options remain limited, and the disease is usually fatal. While TCC can occur in any breed, certain breeds—particularly Scottish Terriers—exhibit a much higher risk, indicating a strong genetic component.
In this 2010 study published in Cancer Research, scientists performed a genome-wide association study (GWAS) involving over 100 dogs with biopsy-confirmed TCC, drawn from three high-risk breeds: Scottish Terriers (ST), West Highland White Terriers (WHWT), and Shetland Sheepdogs (SSD). An additional group of more than 100 control dogs—age 9 or older and cancer-free—served as the comparison group.
The researchers analyzed the data using the Affymetrix v2 canine SNP chip and identified two significant susceptibility loci. Locus1, located in the ST population, showed a powerful association with TCC (p = 5 × 10⁻¹³). Fine mapping across a 4.5 Mb region in this area revealed involvement of genes linked to several cancer pathways, some of which are also commonly deleted in human bladder cancer.
A second genetic hotspot, locus2, was identified in WHWT and SSD (p = 3 × 10⁻⁷). Interestingly, STs showed signs of reduced heterozygosity at locus2 in both affected and unaffected individuals, suggesting the breed may be nearing fixation at this region. This finding may explain their extraordinary twenty-fold risk of developing bladder cancer.
Ongoing work includes resequencing both loci, genotyping an additional 750 SNPs, and investigating potential copy number variations using a custom Goldengate assay. These efforts aim to pinpoint causal mutations and ultimately inform targeted treatments or screening strategies for both veterinary and human medicine.
Because TCC in dogs resembles invasive TCC in humans in both pathology and behavior, this study holds value beyond veterinary science. The identification of canine genetic risk factors may guide the discovery of molecular targets for early detection and therapy in human bladder cancer.
Source: E. Kwon, D. Knapp, P. Bonney, E. McNiel, H. Parker, & E. Ostrander. “Abstract 4746: Mapping genes for invasive urinary bladder cancer in the dog.” Cancer Research, Volume 70, 2010, page 4746. Presented at the 101st Annual Meeting of the American Association for Cancer Research, April 17–21, 2010, Washington, DC.
