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

Departments of Urology [R. A. I., G. A. C.] and Preventive Medicine [M. C. Y., R. K. R.], University of Southern California/Norris Comprehensive Cancer Center, University of Southern California School of Medicine, Los Angeles, California 90033-0804

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 significantly among the races (two-sided P = 0.046 and <0.0005, respectively). The prevalence of short CAG alleles (<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 African-Americans also had the lowest frequency (20%) of the GGC allele with 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 signifiant negative association between 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 alleles (<22 repeats), 43% had long GGC alleles (>16 repeats) whereas only 15% of the 20 subjects with long CAG alleles (22 repeats) had long GGC alleles. Overall, our data suggest a possible association between CAG and GGC microsatellites of the androgen receptor gene and prostate cancer development.

¹ This work was supported in part by Grants P01 CA 17054 and R35 CA 53890 from the National Cancer Institute.

² To whom requests for reprints should be addressed, at University of Southern California/Norris Comprehensive Cancer Center, Room 630A, 1441 Eastlake Avenue, P.O. Box 33804, Los Angeles, CA 90033.

Received 12/ 9/94. Accepted 3/ 2/95.

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