The CAG and GGC Microsatellites of the Androgen Receptor Gene Are in Linkage Disequilibrium in Men with Prostate Cancer1

The androgen receptor genotype was determined in the white blood cell DNA of 45 African-American, 39 non-Hispanic white, and 39 Asian (Chinese, Japanese) normal subjects and 68 patients with prostate cancer (57 whites), all of whom were residents of Los Angeles County. For each subject, we measured the number of repeats in the polymorphic CAG and GGC microsatellites of exon 1 of the androgen receptor gene. In normal subjects, the distributions of CAG and GGC microsatellites differed sig nificantly among the races (two-sided /' = 0.046 and < 0.0005, respective ly). The prevalence of short CAG alÃ-eles«22 repeats) was highest (75%) in African-American males with the highest risk for prostate cancer, intermediate (62%) in intermediate-risk non-Hispanic whites, and lowest (49%) in Asians at very low risk for prostate cancer. High-risk AfricanAmericans also had the lowest frequency (20%) of the GGC alÃ-elewith 16 repeats; the comparable values for intermediate-risk whites and low-risk Asians were 57% and 70%, respectively. Consistent with the interracial variation in CAG and GGC distributions, there was an excess of white patients with <22 CAG and not-16 GGC repeats relative to white controls (relative risk, 2.1; one-sided P = 0.08). We observed no association (linkage) between the two microsatellites among normal subjects. On the other hand, there was a statistically significant negative association be tween the numbers of CAG and GGC repeats among the prostate cancer patients studied (two-sided P = 0.008). Among the 47 subjects with short CAG alÃ-eles «22 repeats), 43% had long GGC alÃ-eles (>16 repeats) whereas only 15% of the 20 subjects with long CAG alÃ-eles( .-22 repeats) had long GGC alÃ-eles. Overall, our data suggest a possible association between CAG and GGC microsatellites of the androgen receptor gene and prostate cancer development.