Polymorphisms of the Canine Androgen Receptor and Association with Prostate Cancer
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The objective of this investigation is to determine whether genetic variation within the androgen receptor gene contributes to variability in the occurrence of prostate cancer in dogs. Understanding the role of the androgen receptor (AR) in initiation and progression of prostate cancer may later advance the prevention and treatment of this disease for both humans and canines. The progression of this disease may be influenced by the efficacy of the transcription-regulatory region of the AR. Within this region of the canine AR exists two poly-glutamine stretches, coded by CAG repeat sequences within the AR gene. We proposed that a shorter poly-glutamine stretch within one or both of these tracts enhances the transcription-regulatory activities of the androgen receptor, and therefore increases the progression of prostate cancer. To investigate this possible association, we examined genomic DNA from high-incidence and low-incidence breeds for the existence of polymorphisms of the AR CAG repeats within and between breeds. The data collected thus far does not demonstrate a higher frequency of the shorter CAG repeat sequence within the high-incidence breeds. Therefore, further examination of AR polymorphisms, through an analysis of DNA of dogs with prostate cancer versus normal dogs, may still provide evidence of our proposed association.