雄激素受体基因（CAG）n重复多态性长度对接受初始内分泌治疗的转移性前列腺癌患者预后的影响

Germline （CAG） n repeat length of androgen receptor among metastatic prostate cancer patients af-ter endocrine therapy

目的探讨雄激素受体（androgenreceptor，AR）基因（CAG）1＂1重复多态性长度与接受初始内分泌治疗的转移性前列腺癌患者预后的关系。方法收集2006年1月至2012年1月接受初始内分泌治疗的转移性前列腺癌患者53例，诊断年龄45～87岁，中位年龄65岁。用PCR和直接测序方法对前列腺癌患者外周血标本进行（CAG）n重复多态性长度测定，结合临床资料分析（CAG）n重复多态性长度与生化无进展生存时间（biochemicalprogressionfreesurvival，bPFS）及总生存时间（overallsurvival，OS）的关系。结果（CAG）n重复多态性长度为14—32，中位长度为21。按（CAG）n中位长度分为（CAG）n≤21组33例和（CAG）n≥22组20例。中位随访36个月。Kaplan—Meier分析显示，与（CAG）n≥22组比较，（CAG）n≤21组患者的bPFS及OS均缩短，差异有统计学意义（P〈O．05）。（CAG）n重复多态性长度是影响转移性前列腺癌患者接受初始内分泌治疗的bPFS（HR2．820，95％C11．466～5．427，P=0．002）和OS（HR5．245，95％CI1．293～21．273，P=0．020）的独立预后因素。结论AR基因（CAG）n重复多态性长度可能影响转移性前列腺癌患者接受初始内分泌治疗的疗效；（CAG）n重复多态性长度≤21预示肿瘤预后不良。

Objective To investigate the clinical significance of （CAG）n repeats length of andro- gen receptor （AR） among the patients with metastatic prostate cancer （TNM1）, and to analyze their rele- vance to survival. Methods This study retrospectively investigated fifty-three metastatic prostate cancer patients aged 65 years （range 45-87） who were initially treated with endocrine therapy. The length of the （CAG） n repeats of blood samples was determined by both PCR sequencing and fragment analysis. The clini- cal significance of （CAG）n repeats and its correlation with biochemical progression free survival （bPFS） and overall survival （OS） were investigated. Results The median length of CAG repeats was 21, ranged from 14 to 32. According to the median （CAG）n repeats length,two groups were divided as （CAG）n ≤ 21 and（CAG） n ≥ 22. The median follow-up was 36 months. Patients with （CAG）n ≤21 had significantly shor- ter OS and bPFS than those with （CAG）n≥ 22 （P 〈0.05）. Shorter CAG repeats remained significant bPFS （HR 2.820, 95%C1 1.466-5.427, P=0.002） and OS （HR 5.245, 95%C1 1.293-21.27, P=0.020） pre- dictor in multivariate analysis. Conclusions The efficacy of endocrine therapy for metastatic prostatecancer patients maybe influenced by the AR-CAG repeats length, and short （CAG） n repeats predict bad prognosis.