We concur with the suggestion of Marcus and colleagues that age at first marijuana use may have an impact on testicular germ cell tumor (TGCT) development.1 Results of analyses addressing this possibility were not presented in our recently published study addressing recreational drug use in relation to risk of TGCTs,2 because data were too sparse to support meaningful analyses addressing this question within the subset of men who developed nonseminoma and their matched controls. We regret that we did not specify this limitation in the original report.
More definitive investigation of age at initiating use of marijuana is among the top priorities for future research, for several reasons. First, peripubertal effects of exogenous cannabinoids on malignant potential of testicular germ cells seem biologically plausible according to the rationale described by Marcus and colleagues, together with the observations that proxy measures of endogenous hormone levels during puberty appear to be associated with TGCT risk3 and that marijuana smoke and the constituent compound Δ-9-tetrahydrocannabinol impact the endocrine axis central to male sexual development4 along the lines discussed in our recent report.2 Second, important mechanistic insights regarding testicular carcinogenesis would be obtained should any effect of marijuana exposure on nonseminoma risk prove to be particularly important in the peripubertal period. Finally, should important effects be confined to the peripubertal period, age could be addressed in future legislation and treatment guidelines pertaining to therapeutic use of cannabinoids.5