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

Abstract

SummaryThe length of the polymorphic CAG repeat in the N-terminal of the androgen receptor (AR) gene is inversely correlated with the transactivation function 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 investigate relations between CAG repeat length and prostate cancer risk, tumour grade, tumour stage, age at diagnosis and response to endocrine therapy. The study included 190 AR alleles from prostate cancer patients and 186 AR alleles from female control subjects. All were whites from southern Sweden. The frequency distribution of CAG repeat length was strikingly similar for cases and controls, and no significant correlation between CAG repeat length and prostate cancer risk was detected. However, for men with non-hereditary prostate cancer (n = 160), shorter CAG repeats correlated with younger age at diagnosis (P = 0.03). There were also trends toward associations between 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 responded better to endocrine therapy, even after adjusting for pretreatment level of prostate-specific antigen and tumour grade and stage (P = 0.05). We conclude that short CAG repeats in the AR gene correlate with young age at diagnosis of prostate cancer, but not with higher risk of the disease. Selection of patients with early onset prostate cancer in case-control studies could 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 good response to endocrine therapy was also found, but the mechanism and clinical relevance are unclear.

The 5α-Reductase Type II A49T and V89L High-Activity Allelic Variants are More Common in Men with Prostate Cancer Compared with the General Population

“…No differences between subjects with diagnosed CaP, men with BPH or men from the general population were found regarding mean-lengths of the polymorphisms in the AR gene, confirming a number of other studies on this topic [28][29][30][31] . However, in current study, short CAG-repeats, i.e.…”

Androgen receptor CAG repeat length contraction in diseased and non-diseased prostatic tissues

“…5,6 Recently, CAG repeat contraction within the AR has been implicated as a possible risk factor in prostate carcinogenesis. 4 Clinically, shortened CAG repeat lengths have been associated with increased risk of developing PCa, [7][8][9][10][11] differing racial predisposition for PCa, 7,9,11 increased clinical aggressiveness of the disease, 8 an early age at diagnosis 12 and as a possible prognostic factor in patients with metastatic disease. 13 These results are, however, controversial, as other studies have failed to support such correlations between AR CAG repeat length and PCa risk.…”

The relationship between the androgen receptor CAG repeat polymorphism length and the response to intermittent androgen suppression therapy for advanced prostate cancer

“…Caucasian and Asian men tend on average, to have longer CAG repeat lengths and a lower risk of developing prostate cancer. 8,9 Short CAG repeat length has also been associated with younger age at diagnosis, 10,11 and increased risk of developing prostate cancer. 9,12,13 Giovannucci et al, 9 and Stanford et al, 14 have also described an association between CAG repeat length and prostate cancer aggressiveness.…”

“…In contrast, a number of studies have not found an association between CAG repeat length and overall risk of prostate cancer, age of diagnosis, or aggressiveness. 8,10,13,[15][16][17] This discrepancy in the significance of the CAG repeat length as a predictor for prostate cancer behaviour may reflect the limited number of studies and small patient numbers, differences in patient selection between studies, technical differences in evaluating the CAG length, or a combination of factors. Standard treatment in advanced prostate cancer involves ADT to halt tumour progression.…”

“…6,7 The clinical evidence to support this relationship, however, is inconclusive. [8][9][10][11][12][13][14][15][16][17] Suzuki et al 18 found that a shorter CAG repeat length predicted for a better response to endocrine therapy. In contrast, Bratt et al 10 reported that a long CAG repeat length predicted for a better response to hormone therapy.…”