Association of marijuana use and the incidence of testicular germ cell tumors

Abstract

Background-The incidence of testicular germ cell tumors (TGCT) has been increasing the past 4-6 decades, but exposures accounting for this rise have not been identified. Marijuana use has also grown over this time period, and chronic marijuana use produces adverse effects on the human endocrine and reproductive systems. We tested the hypothesis that marijuana use is a risk factor for TGCT.

Population‐based case‐control study of recreational drug use and testis cancer risk confirms an association between marijuana use and nonseminoma risk

“…5 Finally, and perhaps most convincingly, the study by Daling et al demonstrated that the risk of developing NTGCT was elevated for subjects who started using marijuana at age 18 years or younger, but it was not found to be elevated for those who started using marijuana after age 18 years. 2 If these data are available to be analyzed from the current study, it would be useful to know whether the results corroborate the findings of Daling et al regarding the impact of age at the time of first marijuana use on the development of NTGCT.…”

Systematic review of the potential role of cannabinoids as antiproliferative agents for urological cancers

“…Daling et al conducted the initial case-control study reporting a 70% increased risk of non-seminoma and mixed histology testicular germ cell tumours among current marijuana (especially among users who started in adolescence) compared to matched controls (odds ratio [OR] 2.3; 95% confidence interval [CI] 1.3-4.0). 4 This initial data was further supported by a recent systematic review and meta-analysis conducted by Gurney et al, which included three case-control studies between 198 and 2015, including a total of 719 cases of testicular germ cell tumours along with 1419 controls. 2,21,22 This study further reinforced the findings of the 2009 case-control study suggesting that current cannabis use at least once weekly or for a long duration (>10 weeks) is associated with the development of testicular germ cell tumour (OR 1.62; 95% CI 1.13-2.31), with the strongest association for non-seminoma tumours.…”

“…The first hypothesis speculates that since endocannabinoids are degraded by fatty acid amid hydrolase while THC is mainly metabolized by cytochrome P 450 enzymes with a half-life of four days in chronic marijuana users, the prolonged activation of CB1 and CB2 in marijuana users can disrupt the normal antitumour activity of the ECS. 4 The second hypothesis is related to the hypothalamus-pituitarytesticular axis. THC typically acts by activating the CB1 and CB2 receptor in the brain to induce a "high."…”

“…3 They mimic many of the effects of THC and activate both CB1 and CB2. 4 The endocannabinoid system (ECS) is widely distributed in mammalian tissues and regulates nervous, cardiovascular, digestive, reproductive, immune, and metabolic functions. 3 Recent studies suggest that cannabinoids contribute to maintaining balance in cell proliferation and that targeting the ECS can affect growth of several different types of cancer, including gliomas, breast, colon, prostate, and hepatocellular carcinoma.…”

Cannabinoid receptor ligands as potential anticancer agents — high hopes for new therapies?

“…However, this statement was recently challenged by a study performed by Aldington and colleagues, [176] which showed that cannabis smoking increased the risk for lung cancer, but it is not certain that cannabinoids are responsible for this correlation. [177] Along the same lines, it is not clear whether chronic marijuana use is correlated with an increased incidence of testicular germ cell tumours [178] because of cannabinoid action. An increasing amount of data shows attenuation of tumour growth by both orally and locally administered cannabinoids in different animal models, raising high hopes for potentially new treatments, in particular in combination with established chemotherapeutic agents (vide supra).…”