A Genetic Link Between Hypothyroidism and T-Zone Lymphoma in Dogs

A genetic mutation may explain why dogs with hypothyroidism are less likely to develop T-zone lymphoma (TZL), according to a genome-wide association study (GWAS) using targeted sequencing.   Not all dogs are equally susceptible to cancer. Certain breeds are more likely to develop the disease than others. One reason is their genetics. Unfortunately, selective breeding based on aesthetic criteria and repeated crossbreeding have had the effect of amplifying genetic predispositions. In particular, Golden Retrievers are prone to numerous cancers, notably T-zone lymphoma. This slowly progressing form of cancer is much more common in Golden Retrievers than in other breeds; they account for 40% of reported cases. Researchers at Colorado State University therefore sought to better understand these associations. In 2019, they published a study establishing links between the environment and the health of these dogs with TZL. The team found that hypothyroidism and omega-3 supplementation are associated with a reduced risk of TZL. They therefore suggested a genetic predisposition to this cancer, which they have now confirmed with a new study. DNA genotyping of dogs at different stages of the disease identified a region of interest on chromosome 8 linked to the development of LST. It turns out that this region is also associated with the regulation of thyroid hormones. The dual discovery—first from the environmental study and then from the genetic study—linking thyroid function to TZL underscores the importance of this part of the canine genome in this disease. Professor Anne Avery of the Department of Microbiology, Immunology, and Pathology at Colorado State University explains: “The relevant genes may be the thyroid function genes themselves or other genes in the region. But these combined findings, which target this genetic region, have convinced us of the importance of this area and that further study of it will yield results.” Other regions have also been identified. The researchers identified four additional variants on chromosome 14 that were associated with an increased risk of developing not only TZL but also mast cell tumors in Golden Retrievers. They suggest a shared mechanism underlying the development of both cancers. This study illustrates the value of combining genetic and environmental risk factors for better cancer management in dogs. The researchers hope that their future work will lead to the development of preventive measures, earlier diagnosis, and effective treatments for all dogs at risk for TZL, not just Golden Retrievers.