Humans and Dogs Share Mammary Cancer Genes

Several forms of neoplasia have known genetic influences. Among the most well known of these are mutations in the human breast cancer genes BRCA1 and BRCA2. Genetic screening is now readily available for patients with a family history of breast cancer to estimate their risk of cancer development.

Veterinary research is starting to identify similar correlations between genetics and neoplasia risk in animals. Researchers in Portugal recently performed a large study to determine whether 14 known human breast cancer genes were associated with development of mammary tumors in canine patients. Their findings were presented in the Journal of Veterinary Diagnostic Investigation.

Study Design

The investigators began by collecting canine blood samples via venipuncture to obtain genomic DNA. Samples came from 212 bitches averaging 10 years of age that were diagnosed with mammary tumors, as well as from 161 bitches averaging 9 years of age with no evidence of mammary neoplasia. Only cancer-free dogs over age 7 were included in the study, placing them in the highest-risk age category for mammary tumor development. Representative breeds for mammary neoplasia (poodle, boxer, Labrador retriever, cocker spaniel, and German shepherd) composed 32% and 22% of the cancer and control groups, respectively; about half of the dogs in each group were mixed breeds.

The following genes associated with human breast cancer susceptibility were examined:

• 2 proto-oncogenes (HER-2, EGFR)
• 2 tumor suppressor genes (TP53, STK11)
• 6 DNA damage recognition and repair genes (BRCA1, BRCA2, RAD51, CHECK2, PTEN, BRIP1)
• 4 hormonal metabolism genes (ESR1, PGR, PRLR, COMT)

Within these genes, the authors examined 67 single-nucleotide polymorphisms (SNPs), which are those individual nucleotide sites most likely to mutate and change DNA traits.

Results

Of the 67 examined SNPs, 3 were significantly associated with canine mammary tumor risk. Of these, 2 SNPs located in the DNA repair gene RAD51 were associated with formation of benign and malignant tumors, whereas 1 mutated SNP in the tumor suppressor gene STK11 was related to development of mostly benign tumors. The investigators determined that none of the 3 SNPs influenced a particular histologic subtype of malignant neoplasia, such as carcinoma, sarcoma, or carcinosarcoma.

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• Enlisting Dogs in the War on Cancer
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The Future of Cancer Research

Comparative oncology is a growing field, revealing that multiple species often share similar cancer traits. For example, the RAD51 gene examined here is already known to interact with the BRCA2 gene in humans and dogs, whereas STK11 has a documented relationship with mammary cancer in cats. These similarities suggest that dogs and cats may be appropriate animal models for human breast cancer research.

Likewise, animals also benefit from our knowledge of human breast cancer traits. By identifying specific nucleotides associated with neoplasia risk, researchers may be able to design diagnostic tests to screen high-risk pets for mammary tumor risk. The authors concluded, “Merging scientific data from human and veterinary oncologic investigation clearly benefits knowledge of cancer development, progression, and management” for all species.

Dr. Stilwell received her DVM from Auburn University, followed by a MS in fisheries and aquatic sciences and a PhD in veterinary medical sciences from the University of Florida. She provides freelance medical writing and aquatic veterinary consulting services through her business, Seastar Communications and Consulting.