Androgens, CAG repeats and prostate cancer in the Bouvier des Flandres

Abstract

Spontaneous prostate cancer (PCA) is known to occur only in humans and in dogs. The disease occurs at advancing age in both species and, similar to late stage PCA in humans, canine prostate tumors are able to grow in an androgen-depleted environment. Serum concentrations of androgens may explain the racial differences in PCA risk in humans. Earlier studies suggest that higher testosterone levels in the Bouvier des Flandres may explain the eight times higher risk of developing PCA in this species. In humans, shorter CAG repeat lengths in the androgen receptor gene have been linked to a higher chance of developing prostate cancer. In dogs, shorter CAG repeat lengths also seem to be associated with a higher chance of developing PCA. In present study, blood samples were taken from 49 Bouviers des Flandres and 44 control dogs. Concentrations of testosterone, DHT and androstenedione were measured using radio immunoassay kits. From the bouviers an other blood sample was taken from which DNA was amplified with a PCR and the product was analyzed with a Genescan to determine CAG repeat lengths. Aim of our study was to investigate the relationship between repeat length and testosterone levels in Bouviers, the differences in androgen levels between Bouviers and control dogs, the relationships between androgens and age and the relations between the different androgens. Furthermore it was investigated if higher testosterone levels in the Bouviers des Flandres are hereditary through pedigree research. Our results show no significant difference in androgen levels between the bouviers and the control group. This suggests that different androgen levels do not explain the breed related difference in the risk of developing PCA between bouviers and other species. We also did not find evidence that having high or low testosterone levels in bouviers is hereditary. Most striking finding in this study is that the relationship between testosterone and androstenedione is stronger in bouviers then in the control group. Whether this is due to a shift in production of androstenedione to the testis, remains to be investigated. The results of the CAG repeat lengths remain to be processed.