Antiepileptic drugs with histone deacetylase inhibition activity and prostate cancer risk: a population-based case-control study

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.