Glycogen synthase kinase-3ß inhibitor use and prostate cancer incidence in Manitoba, Canada: A population-based nested case–control study

Abstract

Background

Little is known on the effect of glycogen synthase kinase-3ß inhibitors (GSK3Is), as a class, on prostate cancer (PC). We aimed to study this in the Canadian province of Manitoba, because mixed results have been reported on the effect of valproate.

Methods

We conducted a nested case-control study among cancer-free Manitobans with ≥ 5 years of medical history in which we matched all men 40 years or older diagnosed with PC between 2000 and 2018 (N = 11,189) on period, age, length of available drug information to cancer-free controls (N = 55,728). We used conditional logistic regression to analyze GSK3I use (lithium, valproate, olanzapine, famotidine). We repeated this analysis for bipolar disorder and for epilepsy, the main indications for GSK3I and performed period, dose, and duration analysis.

Results

Roughly the same proportion of cases and controls were ever-users of GSK3Is (4.0 % vs. 4.5 %). GSK3I use among the general population was associated with a reduced risk of PC (OR=0.81; 95 % CI 0.72–0.91). This effect was seen for both famotidine, 0.87 (0.76–1.00), and olanzapine, 0.72 (0.54–0.96). Valproate appeared to have a protective effect on PC for epilepsy patients (0.35, 0.12–0.99). None of the GSK3Is seem to affect PC risk in bipolar disorder patients.

Conclusion

Possible protection against PC from olanzapine or famotidine is not supported by a period, dose, or duration response and this effect could be due to chance and/or residual confounding. Valproate was possibly associated with a lower risk of PC in epilepsy patients, but a larger analysis would be needed to confirm that this association was not due to chance given the uncertainty in the period, dose, and duration analyses.