Glycogen synthase kinase-3ß inhibitor use and prostate cancer incidence in Manitoba, Canada: A population-based nested case–control study
Bibliographic record
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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".