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Authors Lacson JCA, Carroll JD, Tuazon E, et al.
Review Date October 2012
Citation Cancer 2012; Sep 10. doi: 10.1002/cncr.27554. [Epub ahead of print]
Testicular germ cell tumours (TGCTs) are the most common neoplasm of males aged 15 to 45 years. The incidence of TGCT has increased steadily in recent decades suggesting a change in non-genetic risk factors, but the exact causes of TGCT remain elusive. Germ cell function may be influenced by cannabinoids, and two prior epidemiologic studies have reported that the use of marijuana may be associated with nonseminomatous TGCT. This study provides more data to explore this reported association.
To evaluate the relation between TGCTs and exposure to marijuana and other recreational drugs using a population-based case-control study.
In total, 163 patients who were diagnosed with TGCT in Los Angeles County from December 1986 to April 1991 (81% of eligible cases) were enrolled, and 292 controls (79% of eligible controls) were matched on age, race/ethnicity, and neighbourhood. Participants were asked about drug use by a structured, in-person interview. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression analysis adjusted for history of cryptorchidism; education; religiosity; and reported use of marijuana, cocaine, and amyl nitrite.
Compared with never use, ever use of marijuana had a 2-fold increased risk (OR, 1.94; 95% CI, 1.02-3.68), whereas ever use of cocaine had a negative (inverse) association with TGCT (OR, 0.54; 95% CI, 0.32-0.91). Stratification by tumour histology revealed a specific association of marijuana use with nonseminoma and mixed histology tumours (OR, 2.42; 95% CI, 1.08-5.42) but not with seminomas (OR, 1.07; 95% CI, 0.37-3.07).
A specific association was observed between marijuana use and the risk of nonseminoma and mixed tumours. To the authors’ knowledge, this is the first report of a negative (inverse) association between cocaine use and TGCT risk. The current results warrant mechanistic studies of marijuana’s effect on the endocannabinoid system and TGCT risk and caution that recreational and therapeutic use of cannabinoids by young men may confer malignant potential to testicular germ cells.
Points to Note
- The association reported here between marijuana use and nonseminomatous testicular germ cell tumours supports the findings of two previous case-control studies, although different methods were used.
- Recall bias (i.e. more accurate recall in cases than controls), a potential problem in case-control studies, is not likely to be responsible for the reported association given that the association with cocaine use was in the opposite direction and the association was only seen for nonseminomas.
- This study is reporting old data – testicular cancers diagnosed 20 or so years ago and the most recent data collection was 17 years ago. It is not clear why it has taken so long to publish but it may be in response to similar analyses published in 2009 and 2011.
- The biologic plausibility of an association between marijuana use and nonseminomatous and mixed histology testicular germ cell cancer is not yet defined. However a mechanism involving androgen signalling or response may be implicated given a recent reported link between the active component of marijuana and androgen levels and variations in androgen receptor biology possibly linked to testicular tumour histology.
- The authors suggest possible mechanisms for the association between cocaine use and reduced risk of testicular germ cell tumours but so far there are no other reports of this link. However, the role of cocaine use as a confounder in the association between marijuana use and testicular cancer, identified here, may be important and has not been adjusted for in other studies.
- Given the marijuana-testicular cancer association has now been reported in three studies, investigation of the biological processes may shed more light on the role of marijuana in testicular carcinogenesis.