title: Mammary tumor development in dogs is associated with BRCA1 and BRCA2.
abstract: 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 approximately 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.
authors.affiliation: Department of Clinical Sciences, Division of Small Animal Clinical Sciences, Faculty of Veterinary Medicine and Animal Science, Swedish University of Agricultural Sciences, Uppsala, Sweden. patricio.rivera@kv.slu.se
authors.forename: Patricio
authors.initials: P
authors.lastname: Rivera
authors.forename: Malin
authors.initials: M
authors.lastname: Melin
authors.forename: Tara
authors.initials: T
authors.lastname: Biagi
authors.forename: Tove
authors.initials: T
authors.lastname: Fall
authors.forename: Jens
authors.initials: J
authors.lastname: Häggström
authors.forename: Kerstin
authors.initials: K
authors.lastname: Lindblad-Toh
authors.forename: Henrik
authors.initials: H
authors.lastname: von Euler
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000662:veterinary*; D004285:Dogs; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D006801:Humans; D020641:Polymorphism, Single Nucleotide