CAG repeat length in the androgen receptor gene is related to age at diagnosis of prostate cancer and response to endocrine therapy, but not to prostate cancer risk

The length of the polymorphic CAG repeat in the N-terminal of the androgen receptor (AR) gene is inversely correlated with the transactivation functio n of the AR. Some studies have indicated that short CAG repeats are related to higher risk of prostate cancer. We performed a case-control study to in vestigate relations between CAG repeat length and prostate cancer risk, tum our grade, tumour stage, age at diagnosis and response to endocrine therapy . The study included 190 AR alleles from prostate cancer patients and 186 A R alleles from female control subjects. All were whites from southern Swede n. The frequency distribution of CAG repeat length was strikingly similar f or cases and controls, and no significant correlation between CAG repeat le ngth and prostate cancer risk was detected. However, for men with non-hered itary prostate cancer (n = 160), shorter CAG repeats correlated with younge r age at diagnosis (P = 0.03). There were also trends toward associations b etween short CAG repeats and high grade (P = 0.07) and high stage (P = 0.07 ) disease. Furthermore, we found that patients with long CAG repeats respon ded better to endocrine therapy, even after adjusting for pretreatment leve l of prostate-specific antigen and tumour grade and stage (P = 0.05). We co nclude that short CAG repeats in the AR gene correlate with young age at di agnosis of prostate cancer, but not with higher risk of the disease. Select ion of patients with early onset prostate cancer in case-control studies co uld therefore lead to an over-estimation of the risk of prostate cancer for men with short CAG repeats. An association between long CAG repeats and go od response to endocrine therapy was also found, but the mechanism and clin ical relevance are unclear, (C) 1999 Cancer Research Campaign.