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

Prostate diseases are age and androgen dependent. The evolution of clinically overt pathology requires decades of exposure to adult male levels of circulating testosterone, but the precise relationship between age and androgen circulation remains poorly understood. A marker of integrated androgen action 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 polymorphism 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 prostate cancer. From a larger epidemiologic study of the effects of ethnicity and migration on the origins of prostate disease, a nested-case control study 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 testosterone, estradiol, dihydrotestosterone (DHT), sex hormone-binding globulin (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 volumes compared with Chinese men. Even after adjustment for differences in body size (the Australian men were taller and heavier), the central-zone volume remained lower by approximately 50% in Chinese men (P < 0.001), whereas testis and total-prostate volumes were no longer significantly different. The length 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 correlation 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 difference that persisted after age adjustment (P = 0.039) but that was removed by adjustment for differences in total-prostate size (P = 0.12). Blood testosterone, estradiol, SHBG, and PSA concentrations were not different between 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 androgen sensitivity. Whether either factor alone may constitute a marker of androgen sensitivity remains to be established by other means, and a long-term marker of integrated androgen action suitable for clinical and epidemiologic research is still lacking.