Salminen Jukka K, Tammela Teuvo L J, Auvinen Anssi, Murtola Teemu J
School of Medicine, University of Tampere, Medisiinarinkatu 3, 33014, Tampere, Finland.
Department of Urology, Tampere University Hospital, Tampere, Finland.
Cancer Causes Control. 2016 May;27(5):637-45. doi: 10.1007/s10552-016-0737-2. Epub 2016 Apr 1.
Previous studies suggest that antiepileptic drugs with histone deacetylase (HDAC) inhibitor properties may have prostate cancer preventive effects. We evaluated the association between antiepileptic drug use and prostate cancer risk in a population-based case-control study. The study included all new prostate cancer cases diagnosed in Finland in 1995-2002 and matched controls (24,657 case-control pairs) identified from the Finnish Cancer Registry and the Population Register Center, respectively. Information on antiepileptic drug purchases was obtained from the national prescription reimbursement database. Odds ratios and their 95 % confidence intervals were estimated using age-adjusted and multivariable-adjusted conditional logistic regression analysis. Compared to never-users of antiepileptic drugs, the overall prostate cancer risk was decreased among users of phenobarbital, carbamazepine, and valproic acid (multivariable-adjusted odds ratio (OR) 0.47, 95 % CI 0.24-0.92; OR 0.82, 95 % CI 0.71-0.94, and OR 0.62, 95 % CI 0.42-0.92, respectively), but not among users of other antiepileptic drugs. Overall prostate cancer risk decreased in a dose-dependent manner by cumulative amount, duration and yearly dosage (intensity) of HDAC inhibitors valproic acid and carbamazepine. The risk of advanced prostate cancer was decreased only among carbamazepine users (OR 0.65, 95 % CI 0.44-0.96). Our results support possible prostate cancer preventive effects of HDAC inhibitors. However, also phenobarbital use was associated with decreased prostate cancer risk, despite not having HDAC inhibiting activity. The mechanism of action for antiepileptic drugs in prostate cancer deserves further study.
以往研究表明，具有组蛋白脱乙酰酶（HDAC）抑制特性的抗癫痫药物可能具有预防前列腺癌的作用。我们在一项基于人群的病例对照研究中评估了抗癫痫药物使用与前列腺癌风险之间的关联。该研究纳入了1995 - 2002年在芬兰诊断出的所有新前列腺癌病例以及分别从芬兰癌症登记处和人口登记中心确定的匹配对照（24,657例病例对照对）。抗癫痫药物购买信息来自国家处方报销数据库。使用年龄调整和多变量调整的条件逻辑回归分析估计比值比及其95%置信区间。与从未使用过抗癫痫药物的人相比，苯巴比妥、卡马西平和丙戊酸使用者的总体前列腺癌风险降低（多变量调整后的比值比（OR）分别为0.47，95%置信区间0.24 - 0.92；OR 0.82，95%置信区间0.71 - 0.94，以及OR 0.62，95%置信区间0.42 - 0.92），但其他抗癫痫药物使用者中未出现这种情况。HDAC抑制剂丙戊酸和卡马西平的累积量、使用持续时间和年剂量（强度）使总体前列腺癌风险呈剂量依赖性降低。仅卡马西平使用者的晚期前列腺癌风险降低（OR 0.65，95%置信区间0.44 - 0.96）。我们的结果支持HDAC抑制剂可能具有预防前列腺癌的作用。然而，尽管苯巴比妥没有HDAC抑制活性，但使用苯巴比妥也与前列腺癌风险降低有关。抗癫痫药物在前列腺癌中的作用机制值得进一步研究。
