title: The ESR1 gene is associated with risk for canine mammary tumours.
abstract: BACKGROUND
  The limited within-breed genetic heterogeneity and an enrichment of disease-predisposing alleles have made the dog a very suitable model for the identification of genes associated with risk for specific diseases. Canine mammary cancer is an example of such a disease. However, the underlying inherited risk factors for canine mammary tumours (CMTs) are still largely unknown. In this study, 52 single nucleotide polymorphisms (SNPs) in ten human cancer-associated genes were genotyped in two different datasets in order to identify genes/alleles associated with the development of CMTs. The first dataset consisted of English Springer Spaniel (ESS) CMT cases and controls. ESS is a dog breed known to be at increased risk of developing CMTs. In the second dataset, dogs from breeds known to have a high frequency of CMTs were compared to dogs from breeds with a lower occurrence of these tumours.
  
  
  RESULTS
  We found significant associations to CMT for SNPs and haplotypes in the estrogen receptor 1 (ESR1) gene in the ESS material (best PBonf = 0.021). A large number of SNPs, among them several SNPs in ESR1, showed significantly different allele frequencies between the high and low risk breed groups (best PBonf = 8.8E-32, best PBPerm = 0.076).
  
  
  CONCLUSIONS
  The identification of CMT-associated SNPs in ESR1 in two independent datasets suggests that this gene might be involved in CMT development. These findings also support that CMT may serve as a good model for human breast cancer research.
authors.affiliation: Section of Genetics, Department of Basic Sciences and Aquatic Medicine, Norwegian School of Veterinary Science, P,O Box 8146 Dep,, 0033 Oslo, Norway. KajaSverdrup.Borge@nvh.no
authors.forename: Kaja Sverdrup
authors.initials: KS
authors.lastname: Borge
authors.forename: Malin
authors.initials: M
authors.lastname: Melin
authors.forename: Patricio
authors.initials: P
authors.lastname: Rivera
authors.forename: Stein Istre
authors.initials: SI
authors.lastname: Thoresen
authors.forename: Matthew Thomas
authors.initials: MT
authors.lastname: Webster
authors.forename: Henrik
authors.initials: H
authors.lastname: von Euler
authors.forename: Kerstin
authors.initials: K
authors.lastname: Lindblad-Toh
authors.forename: Frode
authors.initials: F
authors.lastname: Lingaas
mesh_terms: D000483:Alleles; D000818:Animals; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies / Q000662:veterinary; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D015674:Mammary Neoplasms, Animal / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors; D016415:Sequence Alignment / Q000662:veterinary
chemical_list: D047628:Estrogen Receptor alpha