Androgen receptor gene polymorphism and prostate zonal volumes in Australian and Chinese men

Prostate diseases are age and androgen dependent. The evolution of clinical ly overt pathology requires decades of exposure to adult male levels of cir culating testosterone, but the precise relationship between age and androge n circulation remains poorly understood. A marker of integrated androgen ac tion over prolonged periods would therefore be a valuable tool for clinical and epidemiologic research into the origins of prostate disease. In order to evaluate these 2 factors, we have studied the CAG-repeat length polymorp hism of the androgen receptor gene and the size of the total, central, and peripheral zones of the prostate, estimated by planimetric ultrasound in 2 populations with widely different susceptibility to death from invasive pro state cancer. From a larger epidemiologic study of the effects of ethnicity and migration on the origins of prostate disease, a nested-case control st udy was undertaken with 50 Chinese men living in Yue Yang, China and 50 non -Chinese men living in Sydney, Australia. All men had undergone planimetric transrectal prostate ultrasound together with blood sampling to determine CAG-repeat length by polymerase chain reaction and immunoassay of plasma te stosterone, estradiol, dihydrotestosterone (DHT), sex hormone-binding globu lin (SHBG), and prostate-specific antigen (PSA). Australian men had larger central (7.9 +/- 0.4 vs 3.3 +/- 0.3 mL) and total (29.8 +/- 1.2 vs 25.5 +/- 1.1 mL) but not peripheral (22.0 +/- 0.9 vs 22.2 +/- 0.8 mL) prostate volu mes compared with Chinese men. Even after adjustment for differences in bod y size (the Australian men were taller and heavier), the central-zone volum e remained lower by similar to 50% in Chinese men (P < 0.001), whereas test is and total-prostate volumes were no longer significantly different. The l ength of CAG repeats was no different between Australian men (22.5 +/- 0.5 repeats) and Chinese men (22.5 +/- 0.5 repeats), and there was no correlati on within or between populations in CAG repeats or any measure of prostate volume or hormones. DHT concentration was 20% lower in Chinese men compared with Australian men (1.6 +/- 0.1 vs 2.0 +/- 0.1 nmol/L, P = 0.005), a diff erence that persisted after age adjustment (P = 0.039) but that was removed by adjustment for differences in total-prostate size (P = 0.12). Blood tes tosterone, estradiol, SHBG, and PSA concentrations were not different betwe en the 2 populations, Hence, the hypothesis is refuted that the CAG repeat polymorphism in the androgen receptor gene (within the nonpathologic range) and the central-prostate zone volume might be markers of long-term androge n sensitivity. Whether either factor alone may constitute a marker of andro gen sensitivity remains to be established by other means, and a long-term m arker of integrated androgen action suitable for clinical and epidemiologic research is still lacking.