Smoking Marijuana Linked to Increased Risk of Testicular Cancer

Researchers at the University of Southern California (USC) have linked recreational marijuana use to an increased risk of developing testicular germ-cell tumors, the most frequent tumor type in men aged 15 to 45. The study results are published in the journal Cancer, a journal of the American Cancer Society.

The increase in risk for marijuana users was approximately twofold. The current study confirms two previous studies published in Cancer demonstrating a potential link between smoking marijuana and testicular cancer. The same study also found that men who used cocaine had a twofold reduction in risk of testicular cancer.

Researchers at USC have linked recreational marijuana use to an increased risk of developing certain types of testicular cancer

“The risk of testicular germ-cell tumors has been rising for decades, but exposures responsible for the increases have not been identified,” said Victoria Cortessis, MSPH, PhD, one of the authors of the study. Cortessis is an assistant professor of preventive medicine at the Keck School of Medicine of USC in Los Angeles.

The study came together when a colleague of Cortessis, Leslie Bernstein, PhD, director of cancer etiology at the Beckman Research Institute California, chose to analyze exposures that were common among younger men, the main population at higher risk for testicular cancer. Bernstein is also a coauthor of the Cancer article.

“A reason to suspect marijuana in particular,” explained Cortessis, “is that constituents of marijuana smoke have been shown to perturb hormone levels, and hormonal factors have been implicated in testis cancer etiology for some time.” Aside from the potential that marijuana smoke contains testicular carcinogens, previous population-based studies have suggested that those with testicular cancer were more likely to have smoked marijuana.

The results could have implications for providing marijuana and its derivatives as therapy for younger male patients.

Testicular cancer, specifically, testicular germ-cell tumors, are the most common cancer type in men between the ages of 15 and 45. The cancer type is becoming more common. The culprits are believed to be environmental factors, most of which are still unknown. It is important to try to understand the mechanisms that may facilitate development of germ-cell tumors as men with testicular cancer, following treatment, remain at risk for secondary primary tumors as well as cardiovascular disease. An established risk factor is undescended testicles or cryptorchidism.

Currently, evidence points to abnormal steroid levels and effects during both perinatal and peripubertal development as a potential culprit. These abnormalities could stem from exposure to maternal estrogens or environmental hormones during development, for example. Animal studies have found cryptorchidism to be associated with exposure to environmental estrogen exposure. Higher risk of testicular cancer is also linked to severe acne and male pattern baldness, suggesting a man’s varied hormone levels also may play a part.

“There is a growing body of data implicating some organochloride compounds used as pesticides, but much of the increased risk remains unexplained,” said Cortessis, who added that the increased incidence has been observed in various parts of the world.

The Study Results

The population-based case-control study, based in Los Angeles, analyzed the self-reported recreational drug use of 163 young men diagnosed with testicular germ-cell tumors between 1986 and 1991 and compared these to 292 healthy control men of the same age and ethnicity.

The study found that the risk of development of testicular germ-cell tumors in men who reported marijuana use was twofold compared to those who did not smoke. The analysis adjusted for other factors such as education, religion, a history of cryptorchidism, and cocaine and amyl nitrite use. Former marijuana smokers had a higher risk compared to current users. Men who smoked less than once a week were more likely to have testicular germ-cell tumors compared to those who reported no use or higher use of marijuana.

Men diagnosed with testicular cancer were more likely to have had cryptorchidism compared to the control group. Those men who reported use for less than 10 years were more than twice as likely to develop testicular germ-cell tumors compared to nonusers, while those who smoked for over 10 years had a 1.5–fold higher risk that was nonsignificant. This trend has not been previously observed in other studies.

According to Cortessis and coauthors, it is not clear if marijuana can trigger pathways that lead to carcinogenesis in the testis. The endocannabinoid system, important for sperm formation, may be affected, as it is the same cellular network that responds to the active ingredients in marijuana, including delta-9-tetrahydrocannabinol (THC). How cocaine influences testicular cancer risk is a major unknown. On this point, the authors speculate that cocaine may kill sperm-producing germ cells, previously demonstrated in animal models. The current study, according to the authors, is the first epidemiologic study to examine the relationship between cocaine and other drug use and testicular germ-cell tumors risk.

“We have a large, ongoing research program designed to understand the origins of testis cancer,” said Cortessis. “These current results will inform that program as well as the work of other testis cancer researchers.”

Cortessis adds that this study and the two previous studies examining marijuana as a risk factor for testicular cancer suggests that the next step should be to examine the biological processes of how marijuana smoke can affect tumorigenesis in the testes in young men. “The extent to which marijuana and cocaine may influence fertility of young men is an important related question,” said Cortessis.