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The Polymorphic Exon 1 Androgen Receptor CAG Repeat in Men with a Potential Inherited Predisposition to Prostate Cancer¹

Department of Biostatistics, University of Michigan, Ann Arbor, Michigan 48105 [E. M. L., C. D. L.]; Departments of Internal Medicine [E. M. L., H. C., K. B., H. L., K. A. C.], Surgery [K. A. C.], and Pathology [K. J. W.], University of Michigan Medical School, Ann Arbor, Michigan 48109-0946; and Department of Biomathematics, University of California–Los Angeles School of Medicine, Los Angeles, California 90095 [K. L.]

Recent studies have provided epidemiological evidence in support of a possible prostate cancer susceptibility locus on the X chromosome. The androgen receptor (AR) gene, located at Xq11–12, has been implicated as a risk factor for the development of prostate cancer. To examine the potential role of the AR locus in prostate cancer susceptibility, the AR CAG repeat length was measured in 270 Caucasian men with prostate cancer from 133 unrelated families. Each of these families has two or more confirmed cases of prostate cancer occurring in first- and/or second-degree relatives. No evidence for linkage of the AR gene to prostate cancer was observed. We tested for the previously reported association of short CAG alleles with prostate cancer using t tests, Pearson’s ² tests, and logistic regression; analyses were subsequently repeated to incorporate only men with moderate- to high-grade prostate cancer. No association between AR CAG allele length and prostate cancer was detected when either a subset of unrelated patients or a subset of unrelated patients with moderate- to high-grade cancer was compared with a set of unrelated controls. We failed to detect an association between short AR CAG alleles and early age of prostate cancer diagnosis. Once specific hereditary prostate cancer genes have been identified, future studies can more carefully delineate the potential role of this AR polymorphism as a modifier locus in high-risk families.

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