Cannabis use and risk of testicular germ cell tumour: a systematic review and meta-analysis

Objectives: To systematically review and analyse the association of cannabis use with the risk of testicular germ cell tumour (TGCT), as studies have implicated an association between cannabis exposure and an increased risk of developing TGCT. Patients and Methods: The PubMed, Web of Science, and Cochrane Library databases were searched on November 2024 to identify eligible studies according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and the Cochrane Handbook for Systematic Reviews of Interventions. Studies were selected that compared males (P: population) who had cannabis use (I: interventions) to non-users or infrequent users of cannabis (C: comparators) with development of TGCT as the endpoint (O: outcomes) using multivariable analyses that adjusted for the effects of covariates (S: study type). The primary study outcome was the risk of TGCT among cannabis users. Available multivariable odds ratios (ORs) and hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were included in quantitative analysis. Results: A total of 86 articles were identified from our search, of which five were included for qualitative and quantitative analysis. Three studies were case–control and two were cohort in design. Current cannabis use was significantly associated with increased risk of TGCT (OR 1.62, 95% CI 1.13–2.31; P < 0.05 [two studies]), as was long-term (≥10 years) cannabis use (OR 1.68, 95% CI 1.19–2.36; P < 0.05 [three studies]). In subgroup analysis, ever cannabis use was significantly associated with increased risk of non-seminomatous germ cell tumour (NSGCT) (OR 1.71, 95% CI 1.12–2.60; P < 0.05 [two studies]). Conclusion: Our findings highlight cannabis use as a significant modifiable risk factor for the development of TGCT, particularly NSGCT. Given the increasing legalisation and availability of cannabis, further research is necessary to explore the underlying biological mechanisms and to confirm these associations across diverse populations.