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
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
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DOI：
10.1038/sj.bjc.6690746
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发表时间：
1999-10-01
影响因子：
8.8
通讯作者：
Olsson, H
中科院分区：
文献类型：
--
作者：
Bratt, O;Borg, Å;Olsson, H
雄激素受体（AR）基因N端CAG重复多态性的长度与AR的反式激活功能呈负相关。一些研究表明，短CAG重复序列与前列腺癌的高风险有关。我们进行了一项病例对照研究，探讨CAG重复序列长度与前列腺癌风险、肿瘤分级、肿瘤分期、诊断时年龄和内分泌治疗反应之间的关系。该研究包括来自前列腺癌患者的190个AR等位基因和来自女性对照受试者的186个AR等位基因。他们都是来自瑞典南部的白人。CAG重复序列长度的频率分布在病例组和对照组中非常相似，CAG重复序列长度与前列腺癌风险之间没有显著相关性。然而，对于患有非遗传性前列腺癌的男性（n = 160），较短的CAG重复与诊断时的年轻年龄相关（P = 0.03）。短CAG重复序列与高级别（P = 0.07）和高分期（P = 0.07）疾病之间也存在相关趋势。此外，我们发现，即使在调整了预处理的前列腺特异性抗原水平和肿瘤分级和分期后，长CAG重复序列的患者对内分泌治疗的反应更好（P = 0.05）。我们的结论是，AR基因中的短CAG重复序列与前列腺癌诊断时的年轻年龄相关，但与疾病的高风险无关。因此，在病例对照研究中选择早发性前列腺癌患者可能会导致对CAG短重复男性患前列腺癌风险的高估。也发现了长CAG重复序列与对内分泌治疗的良好反应之间的关联，但机制和临床相关性尚不清楚，（C）1999年癌症研究运动。
The 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, (C) 1999 Cancer Research Campaign.