Links between genetic and environmental factors and prostate cancer risk

BACKGROUND. Genetic polymorphisms and expression of steroid receptors may explain why some individuals are more at risk of developing prostate cancer. Some risk factors often discussed are androgen stimulation, and vitamin A and D deficiency. Long GAG-repeats in exon 1 of the androgen receptor (AR) gene on the X chromosome seem to have a protective role against androgen overstimulation. Likewise, long vitamin D receptor alleles in the poly-A tract may prevent vitamin D stimulation. METHODS. Blood samples from 59 Swedish patients with sporadic prostate cancers, 59 with hereditary prostate cancer, and 34 Japanese prostate cancer patients were compared with benign controls. Tissue specimens from 37 Swedish and 23 Japanese prostate cancer patients with matching blood samples were investigated by immunohistochemical techniques. RESULTS. The number of GAG-repeats was identical in sporadic and hereditary prostate cancer patients, but the repeats were significantly shorter than in benign controls. Benign Japanese controls were similar to Swedish controls, but Japanese prostate cancers had longer repeats than did controls. Both the vitamin D and A receptor staining was stronger in Japanese than in Swedish prostate cancer specimens. Prostate cancer occurs approximately 5 years later in Japanese compared with Swedish men. CONCLUSIONS. Varying lengths of GAG-repeats of the androgen receptor cannot fully explain racial differences in clinical prostate cancer incidence. A larger content of vitamin A and D receptors may be linked to a delayed onset of clinical prostate cancer in Japanese men. (C) 1999 Wiley-Liss, Inc.