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Androgen receptor CAG repeat polymorphisms in canine prostate cancer
C-L Lai1, H L'Eplattenier, R van den Ham
1Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, TD Utrecht, The Netherlands.
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 = .001) by an increased proportion of 10 repeats (P = .011) and no 12 repeats (P = .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.
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