Use of antiepileptic drugs and risk of prostate cancer: A nationwide case-control study in Prostate Cancer data Base Sweden


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Gincy George1, Gincy George1, Hans Garmo2, Jan Adolfsson3, Lars Holmberg1, Pär Stattin2, Johan Styrke4, Mieke Van Hemelrijck1
1King’s College London (KCL), 2Other, 3Karolinska Institutet, 4Umeå university

Abstract

Background

Preclinical data and observational studies suggest an inverse association between antiepileptic drug (AED) use and prostate cancer (PCa) risk. In a case-control study based on the Finnish Cancer Registry, AED users had reduced PCa risk compared to never-users. We investigated the association between AED and risk of PCa using a case-control study in Prostate Cancer data Base Sweden (PCBaSe).

Method

All new cases of PCa diagnosed between 2014 and 2016 in PCBaSe were included in the study. Controls were matched to cases on year of birth and county of residence. Exposure to any AED prescription in The Prescribed Drug Registry was assessed. Multivariable conditional logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CI) for risk of PCa associated with AED use, adjusted for civil status, education level and Charlson comorbidity index (CCI). Analyses were stratified by PCa risk categories (low or intermediate and high-risk or metastasis) and duration on AED (< 12 and 12 months).

Results

Among 31591 cases and 156802 controls, 616 (2.0%) cases and 3668 (2.3%) controls were exposed to AEDs. Following adjustment to civil status, education level and CCI, AED exposure was associated with reduced risk of PCa as compared to nerve-users (OR: 0.89; 95% CI: 0.82-0.97). When stratifying on PCa risk categories, an inverse association was observed between AED and high-risk or metastatic PCa (OR: 0.79; 95% CI: 0.68-0.91). No associations were observed for the other PCa risk categories. Stratification based on duration of AED, only showed an association for those on AED for <12 months (OR: 0.88; 95% CI: 0.81-0.97).

Conclusion

Our findings are consistent with previous observational research and preclinical data suggesting reduced risk of PCa in AED users. The reduced risk was not found in AED users with low or intermediate-risk PCa implying that the inverse associations observed are unlikely to be a consequence of diagnostic bias. However, selection bias may have influenced the reduced risk observed in users on shorter AED duration. Further research is required to understand the inverse association observed in high-risk PCa.

Impact statement

Our results support possible PCa preventive effects of AED.