Heavy cannabis use is associated with testicular cancer incidence, researchers reported in the journal Cancer Epidemiology, Biomarkers & Prevention. The finding was limited to heavy use, defined as using cannabis more than 50 times throughout a lifetime. However, the researchers, from Canada, Sweden, and the U.S. National Cancer Institute, found no evidence between men having ever used cannabis and testicular cancer.
“Given current international developments to decriminalize or legalize cannabis use in a number of countries worldwide, it is critically important for legislation initiatives to consider the possible health consequences of cannabis use in the cost-benefit analysis underpinning rational drug policy development,” the authors argued.
The population-based sample of 49,343 Swedish military conscripts aged 18 to 21 years linked conscription questionnaire data about drug use history filled out during 1969 and 1970 with 42 years’ worth of follow-up data from Swedish patient, tumor, and death registries.
A total of 45,250 of the men had reported “ever” having used cannabis, a response that was not associated with subsequent testicular cancer incidence in a multivariate analysis that also included age, cryptorchidism, family history of testicular cancer, tobacco use, and alcohol use.
But the subset of those men who reported “heavy” cannabis use was significantly more likely to be subsequently diagnosed with testicular cancer in multivariate analysis (adjusted hazard ratio [aHR], 2.57; 95% CI: 1.02-6.50). Cryptorchidism was more strongly associated with testicular cancer (aHR, 6.24; 95% CI: 2.30-16.97) but tobacco and alcohol use were not related to testicular cancer incidence.
Data pooled from three previously reported case-control studies similarly found an association between testicular cancer and cannabis use, and particularly strong association between cannabis use and nonseminomatous germ cell tumors, the authors noted.
“Although the current study and the three previous studies have shown a relation between frequency and duration of cannabis use and the development of testicular cancer, the field still lacks evidence of a clear dose-response curve—a prerequisite for establishing a persuasive argument for the causal link,” the authors reported.
Potentially causal biological mechanisms for the reported association are also unclear. However, tetrahydrocannabinol and cannabidiol bind to cannabinoid receptors CB1 and CB2 in the testes and other organs, the researchers noted. In animal experiments, this binding modulates androgen, follicle-stimulating hormone, and luteinizing hormone production.
“Aberration in both steroid hormone levels and gonadotropin levels suggests that cannabinoids may cause a general perturbation of the hypothalamic-pituitary-gonadal axis, which could result in tumorigenesis,” the authors speculated.