The expansion of the CAG repeat in exon 1 of the human androgen receptor gene is associated with uterine endometrial carcinoma.

Uterine endometrial carcinoma is common among women. Several reports indicated that this cancer is influenced by androgens mediated through their receptors. The human androgen receptor gene contains a polymorphic CAG repeat in the coding region of exon 1. Other studies suggested a possible association between the CAG repeat of this gene and the development of several cancers. DNA samples isolated from 29 patients with sporadic endometrial cancer were analyzed for allelic changes in 12 highly polymorphic microsatellite loci on nine chromosomes, containing CAG repeat in the exon 1 of the androgen receptor gene. A significantly high rate of allelic change in the CAG repeat was observed (51.7%) in these patients, although the frequencies of additional loci were similar to those reported by others (0-22.2%). The changed alleles of the tumor tissue were always longer than that of normal tissue except in only one case. Since only one allele on the X chromosome is commonly active in female cells, a differential methylation assay was carried out by using genomic DNA cut with HpaII. In 14 of 15 cases, we found that the activated allele was longer in these samples from tumor tissues than those from normal tissue; in the remaining case, the length of this repeat was unchanged. The expression assays were done by using poly(A+) RNA from tumor and normal uterine tissues, revealing that an activated allele in these tumor tissues was longer than that in the normal tissues in all the cases examined. These findings suggest that expansions of the CAG repeat in the androgen receptor gene may play an important role in the carcinogenesis of uterine endometrial cells. Copyright 2000 Wiley-Liss, Inc.