The CAG repeat within the androgen receptor gene and its relationship to prostate cancer
The CAG repeat within the androgen receptor gene and its relationship to prostate cancer
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DOI：
10.1073/pnas.94.7.3320
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发表时间：
1997-04-01
影响因子：
11.1
通讯作者：
Kantoff, PW
中科院分区：
文献类型：
--
作者：
Giovannucci, E;Stampfer, MJ;Kantoff, PW
雄激素受体基因中出现的多态性 CAG 重复序列的长度与雄激素受体的转录活性呈负相关。由于雄激素刺激的增强可能会增加前列腺癌发生和进展的风险，因此我们研究了雄激素受体基因中较短的 CAG 重复序列是否与较高的前列腺癌风险相关。我们对 1982 年至 1995 年间检测到的 587 例新诊断的前列腺癌病例和 588 例未患前列腺癌的对照组进行了一项巢式病例对照研究，在医生健康研究中，较少的雄激素受体基因 CAG 重复与较高的全前列腺风险之间存在关联[相对风险 (RR) = 1.52； 95%置信区间0.92-2.49； P趋势=0.04；对于 CAG 重复长度小于或等于 18 相对于大于或等于 26 重复的男性]，特别是，较短的 CAG 重复序列与前列腺外扩展或远处转移（C 或 D 期）或高组织学分级（RR = 2.14；CI = 1.14-4.01；P 趋势 = 0.001）为特征的癌症相关，在高分期（RR = 2.23） 和高级别前列腺癌 (RR = 1,89)，重复序列较短的男性患远处转移和致命性前列腺癌的风险特别高，CAG 重复长度的变异性与低级别或低阶段疾病无关。这些结果表明，雄激素受体基因中较短的 CAG 重复序列可预测诊断时前列腺癌的较高级别和晚期阶段以及该疾病的转移和死亡率，临床意义 应进一步评估这些结果。
The length of a polymorphic CAG repeat sequence, occurring in the androgen receptor gene, is inversely correlated with transcriptional activity by the andro gen receptor, Because heightened androgenic stimulation may Increase risk of prostate cancer development and progression, we examined whether shorter CAG repeats in the androgen receptor gene are related to higher risk of prostate cancel. We conducted a nested case-control study of 587 newly diagnosed cases of prostate cancer detected between 1982 and 1995, and 588 controls without prostate cancer, within the Physician's Health Study, An association existed between fewer androgen receptor gene CAG repeats and higher risk of total prostate [relative risk (RR) = 1.52; 95% confidence interval 0.92-2.49; P trend = 0.04; for men with CAG repeat lengths less than or equal to 18 relative to greater than or equal to 26 repeats], In particular, a shorter CAG repeat sequence was associated with cancers characterized hy extraprostatic extension or distant metastases (stage C or D) or high histologic grade (RR = 2.14; CI = 1.14-4.01; P trend = 0.001), This association was observed individually both for high stage (RR = 2.23) and high grade prostate cancer (RR = 1,89), Men with shorter repeats were at particularly high risk for distant metastatic and fatal prostate cancer, Variability in the CAG repeat length was not associated with low grade or low stage disease, These results demonstrate that a shorter CAG repeat sequence in the androgen receptor gene predicts higher grade and advanced stage of prostate cancer at diagnosis, and metastasis and mortality from the disease, The clinical implications of these results should be evaluated further.