The polymorphic CAG repeat in the androgen receptor gene in Jewish Israeliwomen with endometrial carcinoma

BACKGROUND. Endometrial carcinoma is considered a hormonal-dependent tumor; estrogen induces endometrial cellular proliferation, whereas progestines d isplay an and proliferative effect on endometrial tissue. The role that and rogen and its receptor (androgen receptor [AR]) play in the pathogenesis of endometrial carcinoma is less clear. Although androgen has an in vitro inh ibitory effect on endometrial cell proliferation, up to 75% of endometrial carcinoma express AR somatically. A polymorphic CAG repeat within exon 1 of the AR encodes for a polyglutamine tract, with length range of 8 to 33 rep eats, which is inversely correlated with the transcriptional activity of th e AR. METHODS. To gain insight into the role of AR in endometrial carcinoma, the authors analyzed the polymorphic CAG repeat in 79 Jewish Israeli patients , vith endometrial carcinoma as compared with 44 healthy Jewish women serving as controls. Analysis was conducted using germline DNA as template and usi ng polymerase chain reaction primers flanking the CAG repeat with subsequen t fluorescent determination of allele sizes. RESULTS. Allele size range of the longer of the two alleles in the patients was 11-33 (mean, 19.8 +/- 2.7) and in the controls 10-22 (mean, 17.9 +/- 1 .9), a statistically significant difference (P < 0.01). Allele size variati on within the patient group did not correlate with disease stage, grade, re productive history, or age at diagnosis. CONCLUSIONS. The authors conclude that AR-CAG repeat length differs in Jewi sh patients with endometrial carcinoma as compared with healthy individuals in Israel, and this finding increases the possibility that the AR is invol ved in die predisposition to this neoplasm. (C) 2001 American Cancer Societ y.