George Gincy, Garmo Hans, Adolfsson Jan, Elf Kristin, Gedeborg Rolf, Holmberg Lars, Stattin Pär, Styrke Johan, Van Hemelrijck Mieke
Translational Oncology and Urology Research, King's College London, London, UK.
Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
J Oncol. 2023 Feb 15;2023:9527920. doi: 10.1155/2023/9527920. eCollection 2023.
An inverse association between use of antiepileptic drugs (AEDs) and prostate cancer (PCa) has been suggested, putatively due to the histone deacetylases inhibitory (HDACi) properties of the AEDs. In a case-control study in Prostate Cancer data Base Sweden (PCBaSe), PCa cases diagnosed between 2014 and 2016 were matched to five controls by year of birth and county of residence. AED prescriptions were identified in the Prescribed Drug Registry. Odds ratios (ORs) and 95% confidence intervals for risk of PCa were estimated using multivariable conditional logistic regression, adjusted for civil status, education level, Charlson comorbidity index, number of outpatient visits, and cumulative duration of hospital stay. Dose responses in different PCa risk categories and HDACi properties of specific AED substances were further explored. 1738/31591 (5.5%) cases and 9674/156802 (6.2%) controls had been exposed to AED. Overall, users of any AED had a reduced risk of PCa as compared to nonusers (OR: 0.92; 95% CI: 0.87-0.97) which was attenuated by adjustment to healthcare utilisation. A reduced risk was also observed in all models for high-risk or metastatic PCa in AED users compared to nonusers (OR: 0.89; 95% CI: 0.81-0.97). No significant findings were observed for dose response or HDACi analyses. Our findings suggest a weak inverse association between AED use and PCa risk, which was attenuated by adjustment for healthcare utilisation. Moreover, our study showed no consistent dose-response pattern and no support for a stronger reduction related to HDAC inhibition. Further studies focusing on advanced PCa and PCa treatments are needed to better analyse the association between use of AED and risk of PCa.
抗癫痫药物（AEDs）的使用与前列腺癌（PCa）之间存在负相关关系，据推测这是由于AEDs具有组蛋白去乙酰化酶抑制（HDACi）特性。在瑞典前列腺癌数据库（PCBaSe）的一项病例对照研究中，将2014年至2016年期间诊断出的PCa病例按出生年份和居住县与五名对照进行匹配。在处方药登记处识别出AED处方。使用多变量条件逻辑回归估计PCa风险的比值比（ORs）和95%置信区间，并对婚姻状况、教育水平、查尔森合并症指数、门诊就诊次数和住院累计时长进行了调整。进一步探讨了不同PCa风险类别中的剂量反应以及特定AED物质的HDACi特性。1738/31591（5.5%）的病例和9674/156802（6.2%）的对照曾接触过AED。总体而言，与未使用者相比，任何AED的使用者患PCa的风险降低（OR：0.92；95%CI：0.87 - 0.97），这种风险在调整医疗保健利用率后有所减弱。与未使用者相比，在所有模型中，AED使用者中高危或转移性PCa的风险也有所降低（OR：0.89；95%CI：0.81 - 0.97）。在剂量反应或HDACi分析中未观察到显著结果。我们的研究结果表明，AED使用与PCa风险之间存在微弱的负相关关系，这种关系在调整医疗保健利用率后有所减弱。此外，我们的研究未显示出一致的剂量反应模式，也未支持与HDAC抑制相关的更强的降低风险作用。需要进一步开展针对晚期PCa和PCa治疗的研究，以更好地分析AED使用与PCa风险之间的关联。
