Human androgen receptor (AR) gene contains polymorphic CAG repeats in the N-terminal domain that influence transcription efficiency. The CAG repeats encode a poly-glutamine tract, which has a length that is inversely and linearly related to AR activity. It has been observed that longer CAG repeats impose a lower transactivation activity on AR and have a decreased binding affinity for androgens. Androgens have an anti-proliferative effect on endometrial cells. We hypothesize that the length of CAG repeats on the AR gene can predict higher incidence of endometrial cancer. To test this hypothesis, the genetic distributions of CAG repeats on AR gene polymorphisms were investigated in endometrial cancer patients and healthy controls. Genotyping and a chi(2) test revealed that the distribution of CAG repeats was significantly different between the endometrial cancer patients and normal healthy controls (P < 0.001). The endometrial cancer patients had longer alleles than normal healthy controls. The longer CAG repeats in the AR gene may cause a decrease of transactivation function in the receptor, weaken an anti-proliferative effect on uterine endometrial cells, and promote carcinogenesis of the uterine endometrial cells. The findings suggest that the CAG repeats in the AR gene may be important in the carcinogenesis of uterine endometrial cells. (C) 2003 Elsevier Science (USA). All rights reserved.