ANDROGEN RECEPTOR VARIANTS WITH SHORT GLUTAMINE OR GLYCINE REPEATS MAY IDENTIFY UNIQUE SUBPOPULATIONS OF MEN WITH PROSTATE-CANCER

The androgen receptor (AR) contains glutamine (GAG) and glycine (GGC) repeats that are each polymorphic in length. We screened clinically lo calized prostate cancers for somatic mutations in the length of the CA G and GGC repeats in the AR gene and characterized the length of these repeats in the germ-line AR gene, Somatic mutations were rare, and th e range of germ-line repeat lengths in men with prostate cancer was wi thin the range of normal in the general population, Most allele freque ncies in Caucasian men with clinical prostate cancer were remarkably c omparable to those in the general Caucasian population, However, a sub population of the men with clinical prostate cancer had a substantiall y higher frequency of AR alleles with 16 or 17 CAGs (6 of 59 men, 10%) than did the general population (6 of 370 alleles, 1.6%), and a diffe rent subpopulation of the men with prostate cancer had a higher freque ncy of AR alleles with 12 or 13 GGCs (7 of 54 men, 13%) than did the g eneral population (1 of 110 alleles, 0.9%). Of the men with prostate c ancer who had an AR gene with 16 or 17 CAGs, 83% had lymph node-positi ve disease, despite the lack of clinical evidence of metastatic spread , This suggests that a short AR CAG allele may be a risk factor for th e development of clinically unsuspected lymph node-positive prostate c ancer among men under going radical prostatectomy and raises the quest ion of whether this short repeat length played an active role in the d evelopment of aggressive prostate cancer, The odds of having a germ-li ne AR gene with a short CAG repeat (less than or equal to 17 CAGs) wer e substantially higher in Caucasian men with lymph node-positive prost ate cancer than in Caucasian men with lymph node-negative disease or i n the general Caucasian population, The odds of having a short germ-li ne AR CAG were the same for men with lymph node-negative prostate canc er as for the general Caucasian population, The odds of having a germ- line AR gene with a short glycine repeat (less than or equal to 14 GCC s) mere substantially higher in men with prostate cancer than in the g eneral population, but the frequency of alleles with a short GGC repea t was the same in men with lymph node-positive versus lymph node-negat ive disease, This suggests that a short GGC repeat may be a risk facto r for the development of clinical prostate cancer, a hypothesis that n eeds to be tested in cohort and case-control studies.