ANDROGEN RECEPTOR CAG REPEAT LENGTHS IN PROSTATE-CANCER - CORRELATIONWITH AGE-OF-ONSET

The androgen receptor (AR) is a structurally conserved member of the n uclear receptor superfamily. The amino-terminal domain is required for transcriptional activation and contains a region of polyglutamine enc oded by CAG trinucleotide repeats. In humans, the number of CAG repeat s is polymorphic; the average number is 22 in Caucasian males. Expansi on of CAG repeats in the AR has clinical implications for human diseas e. As androgen influences prostate cancer growth, polymorphisms in CAG repeat length may affect the clinical course of patients with prostat e cancer. To test for an association between clinical parameters of hu man prostate cancer and CAG repeat length, we analyzed normal lymphocy te DNA from 109 patients. The CAG region of the AR was amplified by th e PCR. Reaction products were then amplified using end-labeled interna l primers, cut at the internal PstI site and assayed on sequencing gel s using a sequence ladder as a size standard. Sequence analysis of sev eral samples validated this method for measurement of CAG repeat numbe r. The median age of patients was 63 yr (range, 42-83), with 104 Cauca sian, 2 African American, 1 Asian, and 2 other racial origin. The medi an repeat length was 25 for patients with stage A, 22 for patients wit h stage B, 22 for patients with stage C, and 23 for patients presentin g with stage D disease. A significant correlation between CAG repeat l ength and age at onset was observed, whereas correlations with stage, level of prostate-specific antigen at diagnosis, and time to prostate- specific antigen relapse were not significant. Shorter CAG repeat leng ths may be associated with the development of prostate cancer in men a t a younger age. These data suggest that CAG repeat length fan affect the risk of developing prostate cancer.