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 ∼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.

Leveraging Naked Mole Rat (Heterocephalus glaber) Comparative Genomics to Identify Canine Genes Modulating Susceptibility to Tumorigenesis and Cancer Phenotypes

“…Moreover, genetic variation, within particular locations of certain genes has been associated with susceptibility to similar tumors in both humans and dogs. For example, single nucleotide polymorphisms in BRCA1 and BRCA2 have been associated with a four-fold relative risk of mammary tumors in dogs [7] paralleling the identification of the genetic variation within the same genes in human breast cancer [8].…”

Assessment of Prolactin, Steroid Hormone Levels in Tissue Homogenate, Serum and Receptor Distributions in Canine Mammary Tumours

“…Mammary tumours are the most common type of tumour in female dogs, women and cats [1][2][3][4][5][6][7] . Mammary tumours mostly affect middle-aged and elderly bitches [4] , between the age 6 to 10 [3] , median age; 10 to 11 years [6] .…”

“…Mammary tumours mostly affect middle-aged and elderly bitches [4] , between the age 6 to 10 [3] , median age; 10 to 11 years [6] . Approximately 53.3% of the mammary tumours in bitches are malignant [3,6,7] . Although the aetiology of canine mammary tumours is not clear, steroid hormones, some growth factors and their receptors were reported to be responsible for the occurrence of this entity [6] .…”

“…Approximately 53.3% of the mammary tumours in bitches are malignant [3,6,7] . Although the aetiology of canine mammary tumours is not clear, steroid hormones, some growth factors and their receptors were reported to be responsible for the occurrence of this entity [6] . High amounts of SO4E1 detected in canine inflammatory mammary carcinoma (IMC) can be due to the conversion of dehydroepiandrosterone (DHEA), androstenedione and testosterone to oestrone and oestradiol and oestradiol into SO4E1 by enzymes aromatase, steroid sulphatase and estrogen sulfotransferase respectively [8] .…”

Molecular Cloning and Expression of Canine Prolactin Gene

“…Furthermore, half of all canine mammary tumors ultimately become malignant [7,15]. Among many factors that predispose to mammary tumors, prolactin (PRL) was first recognized as a hormone that significantly contributed to both the pathogenesis and progression of rodent mammary neoplasia [18].…”