The ESR1 gene is associated with risk for canine mammary tumours

BMC Veterinary Research

Frode Lingaas⁶  Kerstin Lindblad-Toh³  Henrik von Euler¹  Matthew Thomas Webster⁵  Stein Istre Thoresen²  Patricio Rivera⁴  Malin Melin⁵  Kaja Sverdrup Borge⁶ 

[1] Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden;Section for Clinical Pathology, Department of Basic Sciences and Aquatic Medicine, Norwegian School of Veterinary Science, Oslo, Norway;Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, 02139, USA;Currently: Bagarmossen Animal Hospital, Stockholm, Sweden;Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden;Section of Genetics, Department of Basic Sciences and Aquatic Medicine, Norwegian School of Veterinary Science, P.O Box 8146 Dep., 0033 Oslo, Norway

关键词: Estrogen receptor;    Mammary tumour;    Association;    Risk;    Allele frequency;    Single nucleotide polymorphism;    Dog;   

Others  :  1119569
DOI  :  10.1186/1746-6148-9-69

 received in 2012-10-29, accepted in 2013-03-25,  发布年份 2013

【 摘 要 】

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 P_Bonf = 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 P_Bonf = 8.8E-32, best P_BPerm = 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.

【 授权许可】

   
2013 Borge et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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