Use of Antiepileptic Drugs and Risk of Prostate Cancer: A Nationwide Case-Control Study in Prostate Cancer Data Base Sweden

Gincy George; Hans Garmo; Jan Adolfsson; Kristin Elf; Rolf Gedeborg; Lars Holmberg; Pär Stattin; Johan Styrke; Mieke Van Hemelrijck

doi:10.1155/2023/9527920

Use of Antiepileptic Drugs and Risk of Prostate Cancer: A Nationwide Case-Control Study in Prostate Cancer Data Base Sweden

J Oncol. 2023 Feb 15:2023:9527920. doi: 10.1155/2023/9527920. eCollection 2023.

Authors

Gincy George¹, Hans Garmo^{1

2}, Jan Adolfsson³, Kristin Elf⁴, Rolf Gedeborg², Lars Holmberg^{1

2}, Pär Stattin², Johan Styrke⁵, Mieke Van Hemelrijck¹

Affiliations

¹ Translational Oncology and Urology Research, King's College London, London, UK.
² Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
³ Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
⁴ Clinical Neurophysiology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
⁵ Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden.

Abstract

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.