Dataset Information

Canine mammary tumor risk is associated with polymorphisms in RAD51 and STK11 genes.

ABSTRACT: Cancer is a complex disease involving genetic and phenotypic changes. Several single nucleotide polymorphisms (SNPs) have been associated with the risk of breast cancer development in women; however, little is known regarding their influence on canine mammary tumor risk. We assessed the influence of SNPs in genes related to human breast cancer susceptibility, with respect to the risk of development of mammary tumors in dogs. Sixty-seven canine SNPs in proto-oncogenes, tumor suppressor genes, genes involved in DNA repair, and in hormonal metabolism were evaluated in 212 bitches with mammary tumors and in 161 bitches free of mammary neoplasia. A significant association with mammary neoplasia risk was identified for 2 SNPs in RAD51 ( rs23623251 and rs23642734) and one SNP in the STK11 gene ( rs22928814). None of the other SNPs were related to the risk of mammary tumor development. The identification of genetic profiles associated with risk of mammary neoplasia is of great importance, supporting the implementation of specific clinical management strategies in high-risk animals.

SUBMITTER: Canadas A

PROVIDER: S-EPMC6505793 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Canine mammary tumor risk is associated with polymorphisms in RAD51 and STK11 genes.

Canadas Ana A Santos Marta M Nogueira Augusto A Assis Joana J Gomes Mónica M Lemos Carolina C Medeiros Rui R Dias-Pereira Patrícia P

Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc 20180720 5

Cancer is a complex disease involving genetic and phenotypic changes. Several single nucleotide polymorphisms (SNPs) have been associated with the risk of breast cancer development in women; however, little is known regarding their influence on canine mammary tumor risk. We assessed the influence of SNPs in genes related to human breast cancer susceptibility, with respect to the risk of development of mammary tumors in dogs. Sixty-seven canine SNPs in proto-oncogenes, tumor suppressor genes, gen ...[more]

PMID: 30027822

Similar Datasets

Project description:Background Although, in general, cancer is considered a multifactorial disease, clustering of particular cancers in pedigrees suggests a genetic predisposition and could explain why some dog breeds appear to have an increased risk of certain cancers. To our knowledge, there have been no published reports of whole genome sequencing to investigate inherited canine mammary tumor (CMT) risk, and with little known about CMT genetic susceptibility, we carried out whole genome sequencing on 14 purebred dogs diagnosed with mammary tumors from four breed-specific pedigrees. Following sequencing, each dog’s data was processed through a bioinformatics pipeline. This initial report highlights variants in orthologs of human breast cancer susceptibility genes. Results The overall whole genome and exome coverage averages were 26.0X and 25.6X, respectively, with 96.1% of the genome and 96.7% of the exome covered at least 10X. Of the average 7.9 million variants per dog, initial analyses involved surveying variants in orthologs of human breast cancer susceptibility genes, BRCA1, BRCA2, CDH1, PTEN, STK11, and TP53, and identified 19 unique coding variants that were validated through PCR and Sanger sequencing. Statistical analyses identified variants in BRCA2 and STK11 that appear to be associated with CMT, and breed-specific analyses revealed the breeds at the highest risk. Several additional BRCA2 variants showed trends toward significance, but have conflicting interpretations of pathogenicity, and correspond to variants of unknown significance in humans, which require further investigation. Variants in other genes were noted but did not appear to be associated with disease. Conclusions Whole genome sequencing proves to be an effective method to elucidate risk of CMT. Risk variants in orthologs of human breast cancer susceptibility genes have been identified. Ultimately, these whole genome sequencing efforts have provided a plethora of data that can also be assessed for novel discovery and have the potential to lead to breakthroughs in canine and human research through comparative analyses.

Dataset Information

Canine mammary tumor risk is associated with polymorphisms in RAD51 and STK11 genes.

Publications

Canine mammary tumor risk is associated with polymorphisms in RAD51 and STK11 genes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets