Prostate cancer progression – What can be learnt from global populations?

Prostate cancer (Pca) is the most commonly diagnosed non-skin cancer in men, the incidence, however, displays a high degree of variability according to race. The highest incidence of Pca occurs in men of African descent and the mortality rate in this racial group is 2 fold higher than in Caucasian men. This increased mortality risk amongst black men has been attributed to a greater propensity for aggressive non-differentiated Pca, due to an increased sensitivity to testosterone via transactivation of the androgen receptor (AR). The AR has been found to contain truncated polyglycine (CAG) repeats, which correspond functionally to an increased potential for transactivation by other mitogenic factors. The length of such repeats has also been found to be proportional to the age at diagnosis, with shorter repeats leading to earlier onset of the disease. The aim of this investigation was to characterise the CAG repeat in African and Caucasian patients and correlate repeat number with PSA levels. The results indicated that there was a significant correlation between CAG repeat number and PSA across the cohort (P= 0.04). Additionally, there was a significant correlation (P= 0.05) between stage of disease and repeat number in the Caucasian samples that was not observed in the African samples. This may indicate that CAG truncation predisposes the individual to more aggressive Pca and could therefore be utilised as a prognostic marker in Caucasian populations. The lack of correlation between stage and repeat number in the African samples may indicate a population specific predisposition to aggressive Pca