Polymorphic repeats in the androgen receptor gene in high‐risk sibships

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Abstract
Background: Genetic susceptibility may explain some familial clusters of prostate cancer. The polymorphic androgen receptor (AR) gene, which mediates androgen activity in the prostate, is a candidate gene that may influence predisposition to the disease.Methods: We analyzed the polymorphic (CAG)n and (GGN)n repeats within the AR gene in men from 51 high‐risk prostate cancer sibships, which included at least one affected and one unaffected man (n = 210). We compared repeat lengths of men with prostate cancer (n = 140) to their brothers (n = 70) without disease, stratified by median age at diagnosis of affected men within each sibship. Conditional logistic regression was used to compute odds ratios (OR) and 95% confidence intervals to evaluate associations between prostate cancer and repeat length.Results: The OR for prostate cancer associated with short (CAG)n repeats (<22) compared to longer repeats (≥22) was 1.13 (95% CI 0.5–2.4) overall, but was higher in sibships with a median age of <66 years at diagnosis (OR = 1.72, 95% CI 0.5–6.0). The (GGN)n array also was not associated with prostate cancer in general. However, in older men (≥66 years), there was a modest elevation in risk (OR = 1.56, 95% CI 0.6–4.1) among those with short repeats (GGN of ≤16). Men with both a short (CAG)n (16)].Conclusions: These results suggest that the (CAG)n and (GGN)n repeats in the AR gene do not play a major role in familial prostate cancer. Prostate 48:200–205, 2001.