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

Abstract

Background Testicular germ cell tumor (TGCT) incidence increased steadily in recent decades, but causes remain elusive. Germ cell function may be influenced by cannabinoids, and two prior epidemiologic studies report that use of marijuana may be associated with non-seminomatous TGCT. Here we evaluate the relationship between TGCTs and exposure to marijuana and other recreational drugs using a population-based case-control study. Methods 163 TGCT cases diagnosed in Los Angeles County from December 1986 to April 1991 were enrolled with 292 controls matched on age, race/ethnicity and neighborhood. Participants were asked about drug use by structured in-person interview. Odds ratios and 95% confidence intervals were estimated using conditional logistic regression, adjusted for history of cryptorchidism; education; religiosity; and reported use of marijuana, cocaine and amyl nitrite. Results Compared to never use, ever use of marijuana had two-fold increased risk (OR=1.94, 95%CI: 1.02–3.68) while ever use of cocaine was negatively associated with TGCT (OR=0.54, 95%CI: 0.32–0.91). Stratification on tumor histology revealed a specific association of marijuana use with non-seminoma and mixed histology tumors (OR=2.42, 95%CI: 1.08–5.42). Conclusions We observed a specific association of marijuana use with risk of non-seminoma and mixed tumors. This is the first report of a negative association between cocaine use and TGCT risk. Results warrant mechanistic studies of marijuana’s effect on the endocannabinoid system and TGCT risk, and caution that recreational and therapeutic cannabinoids by young men may confer malignant potential to testicular germ cells.

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

“…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.…”

Marijuana, phytocannabinoids, the endocannabinoid system, and male fertility

“…However, a number of animal studies have reported direct effects on various reproductive organs. Prolonged cannabis exposure reduced the ventral prostate, seminal vesicle, and epididymal weights in both rats and mice [96][97][98][99][100]. These findings were accompanied by histological evidence showing disruption of the basement membrane, significant shrinkage of the seminiferous tubules marked by appearance of giant cells in their lumen, reduction in the number of spermatogonia, and furthermore spermatogenic cells showing degeneration, vacuolated/scanty cytoplasm, and small dense nuclei.…”

“…The authors went on to caution that recreational and therapeutic use of cannabinoids by young men may confer malignant potential to testicular germ cells [97].…”

Testicular cancer in two brothers of a quadruplet: a case report and a review of literature

“…Other risk factors are small birth weight, small gestational age, inguinal hernia, twinning (7), adult height, and a low BMI (8, 9) -possibly as proxies of the birth-cohort effect. Somewhat less relevant are professional (firefighting, aircraft maintenance) and environmental (organochloride pesticides, marijuana use) risk factors (10,11).…”