长期雄激素剥夺治疗前列腺癌的男性患结直肠癌的风险。
Risk of colorectal cancer in men on long-term androgen deprivation therapy for prostate cancer.
机构信息
Department of Medical Oncology, Kantonsspital, St Gallen, Switzerland.
出版信息
J Natl Cancer Inst. 2010 Dec 1;102(23):1760-70. doi: 10.1093/jnci/djq419. Epub 2010 Nov 10.
BACKGROUND
Androgen deprivation with gonadotropin-releasing hormone (GnRH) agonists or orchiectomy is a common but controversial treatment for prostate cancer. Uncertainties remain about its use, particularly with increasing recognition of serious side effects. In animal studies, androgens protect against colonic carcinogenesis, suggesting that androgen deprivation may increase the risk of colorectal cancer.
METHODS
We identified 107 859 men in the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database who were diagnosed with prostate cancer in 1993 through 2002, with follow-up available through 2004. The primary outcome was development of colorectal cancer, determined from SEER files on second primary cancers. Cox proportional hazards regression was used to assess the influence of androgen deprivation on the outcome, adjusted for patient and prostate cancer characteristics. All statistical tests were two-sided.
RESULTS
Men who had orchiectomies had the highest unadjusted incidence rate of colorectal cancer (6.3 per 1000 person-years; 95% confidence interval [CI] = 5.3 to 7.5), followed by men who had GnRH agonist therapy (4.4 per 1000 person-years; 95% CI = 4.0 to 4.9), and men who had no androgen deprivation (3.7 per 1000 person-years; 95% CI = 3.5 to 3.9). After adjustment for patient and prostate cancer characteristics, there was a statistically significant dose-response effect (P(trend) = .010) with an increasing risk of colorectal cancer associated with increasing duration of androgen deprivation. Compared with the absence of these treatments, there was an increased risk of colorectal cancer associated with use of GnRH agonist therapy for 25 months or longer (hazard ratio [HR] = 1.31, 95% CI = 1.12 to 1.53) or with orchiectomy (HR = 1.37, 95% CI = 1.14 to 1.66).
CONCLUSION
Long-term androgen deprivation therapy for prostate cancer is associated with an increased risk of colorectal cancer.
背景
促性腺激素释放激素（GnRH）激动剂或睾丸切除术的雄激素剥夺是治疗前列腺癌的常用但有争议的方法。其使用仍存在不确定性，特别是随着对严重副作用的认识不断增加。在动物研究中，雄激素可预防结肠致癌作用，这表明雄激素剥夺可能会增加结直肠癌的风险。
方法
我们在链接的监测、流行病学和最终结果（SEER）-医疗保险数据库中确定了 1993 年至 2002 年间诊断为前列腺癌的 107859 名男性，随访至 2004 年。主要结局是结直肠癌的发展，通过第二原发癌的 SEER 文件确定。使用 Cox 比例风险回归评估雄激素剥夺对结局的影响，调整了患者和前列腺癌特征。所有统计检验均为双侧检验。
结果
接受睾丸切除术的男性未调整的结直肠癌发病率最高（6.3/1000 人年；95%置信区间[CI] = 5.3 至 7.5），其次是接受 GnRH 激动剂治疗的男性（4.4/1000 人年；95%CI = 4.0 至 4.9）和未接受雄激素剥夺治疗的男性（3.7/1000 人年；95%CI = 3.5 至 3.9）。调整患者和前列腺癌特征后，存在统计学上显著的剂量反应效应（P(trend) =.010），随着雄激素剥夺持续时间的增加，结直肠癌的风险逐渐增加。与不使用这些治疗方法相比，使用 GnRH 激动剂治疗 25 个月或更长时间（危险比[HR] = 1.31，95%CI = 1.12 至 1.53）或睾丸切除术（HR = 1.37，95%CI = 1.14 至 1.66）与结直肠癌的风险增加相关。
结论
前列腺癌的长期雄激素剥夺治疗与结直肠癌风险增加相关。
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