Catechol-o-methyltransferase genotypes are associated with progression and biological behaviour of canine mammary tumours

The enzyme catechol-o-methyltransferase (COMT) is responsible for inactivation of catechol estrogens, which are well-recognized carcinogenic metabolites. Two single-nucleotide polymorphisms (SNPs) in canine COMT gene were previously associated with the age of onset of mammary tumours and with the clinical progression of the disease. However, no information is available regarding the impact of other known SNPs in COMT gene in canine mammary tumours. The aim of the present study is to evaluate the influence of COMT SNP in clinicopathological features and outcome of canine mammary tumours. A case series study was conducted involving 155 non-neutered bitches with mammary tumours submitted to follow-up for 24 months after surgery. Three genotypes were considered: Genotype 1 (rs853046495); Genotype 2 (rs23350589, rs23322686, rs23336579, and rs852564758); Genotype 3 (rs851328636 and rs853133060). Genotype 1 was associated to low degree of tubular differentiation. Genotype 2 was related to the development of intermediate/high-histological-grade carcinomas and to vascular invasion. Genotype 3 was associated to reduced nuclear pleomorphism and well-differentiated carcinomas. Data from the present investigation allowed the identification of COMT genetic profiles associated with pathological features of mammary tumours that constitute relevant prognostic factors. The assessment of the COMT genotypes may represent a helpful tool in the clinical management of canine mammary tumours, assisting in the selection of individualized preventive and therapeutic strategies, according to the animals' genetic profile.