ABCB1 gene variations and risk of mammary tumors in dogs

Abstract

The ABCB1 gene encodes the P-glycoprotein (P-gp) which regulates distribution and bioavailability of many endogenous and exogenous substrates, acting as a cellular mechanism of protection against these substances. Some studies have shown evidence that P-gp is related to carcinogenesis. In this study, we performed PCR and direct sequencing of ABCB1 exons 9 and 26 in 47 tissue DNA samples from canine mammary tumors. A statistically significant correlation between distinct canine breeds and the frequency of ABCB1 polymorphisms (c.985T > A and c.3442A > G SNP in ABCB1exons 9 and 26, respectively) was observed (P = 0.0015). In contrast, the TNM clinical staging, age, histological type and grade, as well as other histopathological characteristics, did not present statistically significant difference in relation to one or both SNP found in exons 9 and 26. These findings raise questions about the role of the canine ABCB1 polymorphisms in the development of mammary tumors, since the Poodle breed, which is the most common dog breed affected by mammary tumors in Brazil, presented the highest frequency of these variants. Notwithstanding, additional studies comprising a number of samples expressing the ABCB1 gene from healthy dogs, with advanced age and from different breeds, will be necessary to confirm the association of ABCB1polymorphisms and the development of mammary tumors.