Cannabis use and testicular germ cell tumour subtypes in the french nationwide TESTIS case-control study.
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BACKGROUND: Testicular germ cell tumours (TGCTs) are the most common malignancy among young men, and their rapidly increasing incidence suggests a role for modifiable risk factors. The role of increasingly prevalent cannabis use, particularly during developmental periods before biological maturation, in TGCT etiology remains unclear. METHODS: The association between cannabis use in adolescence and early adulthood and TGCT was assessed in a nationwide hospital-based case-control study in France (454 cases, 670 controls). Exposure was characterized by timing and frequency, including persistent use. Weekly-equivalent exposure scores were used to approximate exposure-response. Conditional logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs), overall and by histological subtype. RESULTS: Cannabis use was not consistently associated with TGCT risk overall. Associations varied by timing and histological subtype. Early adulthood daily use was associated with increased TGCT risk overall (OR baseline=1.50, CI 1.02-2.19) and with seminoma (OR baseline=2.02, CI 1.22, 3.33; OR adjusted=1.93, CI 1.13-3.31), adjusted for tobacco, alcohol, and education. Exposure-response was observed in early adulthood (p-trend = 0.046), particularly for seminoma (p-trend = 0.016). Weekly use across 12-25 years was associated with increased TGCT risk (OR adjusted=1.85, CI 1.11-3.07), with similar patterns for seminoma (OR adjusted=2.29, CI 1.09-4.79). No associations were observed in adolescence or for non-seminoma. CONCLUSIONS: Findings support an effect of cannabis use during early adulthood on TGCT risk with significant dose-response relationships and stronger associations for daily use, particularly for seminoma; however, subtype results require cautious interpretation and independent confirmation.