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Mammary Tumor Development in Dogs Is Associated with BRCA1 and BRCA2

¹ Department of Clinical Sciences, Division of Small Animal Clinical Sciences, Faculty of Veterinary Medicine and Animal Science and ² Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences (SLU); ³ Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden and ⁴ Broad Institute of Harvard and MIT, Cambridge, Massachusetts

Requests for reprints: Patricio J. Rivera, Department of Clinical Sciences, Faculty of Veterinary Medicine and Animal Science, Swedish University of Agricultural Sciences (SLU), P.O. Box 7054, S-750 07 Uppsala, Sweden. Phone: 46-18-67-29-57; Fax: 46-18-67-35-34; E-mail: patricio.rivera{at}kv.slu.se.

Breast cancer is a major contributor to overall morbidity and mortality in women. Several genes predisposing to breast cancer have been identified, but the majority of risk factors remain unknown. Even less is known about the inherited risk factors underlying canine mammary tumors (CMT). Clear breed predispositions exist, with 36% of English springer spaniels (ESS) in Sweden being affected. Here, we evaluate 10 human breast cancer genes (BRCA1, BRCA2, CHEK2, ERBB2, FGFR2, LSP1, MAP3K1, RCAS1, TOX3, and TP53) for association with CMTs. Sixty-three single-nucleotide polymorphisms (SNPs; four to nine SNPs per gene) were genotyped by iPLEX in female ESS dogs, 212 CMT cases and 143 controls. Two genes, BRCA1 and BRCA2, were significantly associated with CMT (Bonferroni corrected P = 0.005 and P = 0.0001, respectively). Borderline association was seen for FGFR2. Benign and malignant cases were also analyzed separately. Those findings supported the association to BRCA1 and BRCA2 but with a stronger association to BRCA1 in malignant cases. Both BRCA1 and BRCA2 showed odds ratios of 4. In conclusion, this study indicates that BRCA1 and BRCA2 contribute to the risk of CMT in ESS, suggesting that dogs may serve as a good model for human breast cancer. [Cancer Res 2009;69(22):8770–4]

Key Words: breast cancer • candidate gene • comparative model