Association between DLA-DRB1.2 allelic diversity and development of mammary gland tumors in dogs

Background: The major histocompatibility complex (MHC) is the best-characterized genetic region related to resistance/susceptibility to a wide range of infectious and immune-mediated diseases. Evidences suggest that MHC class II genes may play an important role in developing different types of tumors including breast cancer. Canine mammary gland tumors (CMTs) are the most common neoplasms in female dogs. In the current study, the association of canine MHC class II DLA-DRB1.2 genotypes with development of mammary gland tumor profiles in dogs was investigated. DLA-DRB1.2 allelic diversity was determined in 40 dogs (18 CMT cases and 22 controls) using HRM technique and DNA sequencing. Association of the DLA-DRB1.2 genotypes with CMT profiles was expressed as odds ratio (OR).

Results: Based on the histopathological typing of tumors, CMT cases were categorized into 4 groups: simple carcinoma, complex carcinoma, carcinoma arising in a benign tumor and special types of carcinoma. A total of eight HRM profiles (A to H) were identified in dogs sampled. The association study revealed a significant correlation between DLA-DRB1.2 genotypes with different CMT profiles. The E genotype was significantly associated with increased risk of carcinoma arising in a benign tumor, and the B genotype represented a positive correlation with complex carcinoma. Significant association was also observed between the heterozygosity of DLA-DRB1.2 genotypes and decreased risk of developing tumor in dogs.

Conclusions: These results provide additional support for the association between DLA-DRB1 genes and development of mammary gland tumors in dogs and could potentially be used for early diagnosis of neoplasia and identifying susceptible dogs.