Androgen Receptor CAG Repeat Polymorphisms in Canine Prostate Cancer

Abstract

Background: Relatively shorter lengths of the polymorphic polyglutamine repeat-1 of the androgen receptor (AR) have been associated with an increased risk of prostate cancer (PC) in humans. In the dog, there are 2 polymorphic CAG repeat (CAGr) regions.Objective: To investigate the relationship of CAGr length of the canine AR-gene and the development of PC. Animals: Thirty-two dogs with PC and 172 control dogs were used. Methods: DNA was extracted from blood. Both CAG repeats were amplified by polymerase chain reaction (PCR) and PCR products were sequenced.Results: In dogs with PC, CAG-1 repeat length was shorter (P 5 .001) by an increased proportion of 10 repeats (P 5 .011) and no 12 repeats (P 5 .0017) than in the control dogs. No significant changes were found in CAG-3 length distribution. CAG-1 and CAG-3 polymorphisms proved not to be in linkage disequilibrium.Breed difference in allelic distribution was found in the control group. Of the prostate-disease sensitive breeds, a high percentage (64.5%) of the shortest haplotype 10/11 was found in the Doberman, whereas Beagles and German Pointers had higher haplotype 12/11 (47.1 and 50%). Bernese Mountain dogs and Bouvier dogs both shared a high percentage of 11 CAG-1 repeats and 13 CAG-3 repeats. Differences in (combined) allelic distributions among breeds were not significant.Conclusions and Clinical Importance: In this preliminary study, short CAG-1 repeats in the AR-gene were associated with an increased risk of developing canine PC. Although breed-specific differences in allelic distribution of CAG-1 and CAG-3 repeats were found, these could not be related to PC risk.

Association between decreased expression of estrogen receptor alpha, androgen receptor and phosphatase and tensin homolog immunoexpression in the canine prostate

“…An important difference between both species is that dogs show higher incidence of androgen independent tumors than humans (Bryan et al 2007). Neutered dogs have an increased risk of developing PC and they usually develop tumors from androgen independent cell (Lai et al 2008).…”

The place of androgen receptor gene mutation analysis in the molecular diagnosis of prostate cancer and genotype–phenotype relationship

“…Accordingly, most description are concerned with short alleles with polyglutamine tract glutamine residues on the receptor, which can do more high transactivation, depending on the inverse relationship with transcriptional activity (15). This potential relationship can be modified with the stage/degree at diagnosis (16) and the men who were diagnosed at more advanced ages seem to have longer CAG repeats (17), while 2 studies found no statistically significant relationship between short CAG length and formation of prostate cancer (18,19). Bratt et al (11) determined the relationship between CAG repeats and diagnosis at a young age, but did not find a relationship with high risk.…”

Das Prostatakarzinom des Hundes

“…Das Prostatakarzinom entsteht aus den Basalzellen des Epithels der Ductuli [18,34]. Mögliche Ursachen sind in der Genetik und in der Immunhistologie zu suchen [22,23,32,33,34,51,52].…”