The study of 455 Californian men found those who had smoked pot were twice as likely to have been diagnosed with testicular germ cell tumors, the most common form of testicular cancer in men younger than 35.
"Testicular cancer is on the rise," said study author Victoria Cortessis, assistant professor of preventive medicine at the University of Southern California's Keck School of Medicine in Los Angeles. "So we asked, 'What is it that young men are doing more frequently that could account for the increased risk?'"
Cortessis and colleagues used interviews to probe recreational drug use among 163 men diagnosed with testicular cancer and 292 healthy men of the same age, and found those who smoked marijuana had double the risk of testicular tumors compared with men who passed on grass. On top of that, their tumors tended to be faster-growing and tougher to treat.
"Most men who get testicular cancer today survive, and that's wonderful. But as a result of treatment, they may have problems with fertility or sexual function," said Cortessis. "So we're talking about the risk of developing the cancer in the first place as well as the subsequent effects of the cancer and its treatment."
The study, published today in the journal Cancer, adds to mounting evidence that smoking marijuana may have lasting effects on men's fertility and overall health.
"We now have three studies connecting marijuana use to testicular cancer, and no studies that contradict them," said Stephen Schwartz, an epidemiologist at the Fred Hutchinson Cancer Center in Seattle and author of the first study linking marijuana use to testicular cancer in 2009. "I think we should start taking notice."
The National Cancer Institute estimates more than 8,500 men will be diagnosed with testicular cancer in 2012. About 360 of them will die from it.
But how marijuana affects the risk of testicular cancer is unclear. In animal studies, marijuana smoke and the cannabis chemical tetrahydrocannabinol, or THC, reduce levels of circulating hormones like testosterone.
"We know testosterone is an important regulator of testes development and function," said Cortessis. "It may be that marijuana use disrupts this regulation in a way that makes the testes much more vulnerable to cancer."
Cortessis suspects boys who experiment with marijuana during puberty might be particularly susceptible. In her study, the risk of testicular cancer was higher among men who smoked less than once a week and for fewer than 10 years.
"Guys who tried it and abandoned it may have been very young," she said, adding that her study was too small to tease out age-related risks. "We plan to investigate the possibility that men who use marijuana during puberty may be especially vulnerable, which makes sense if marijuana is disrupting the hormone signaling that directs the testes to maturity."
But other factors could be at play, as men who use marijuana are more likely to drink and use other drugs. However, Cortessis found men who used cocaine were actually less likely to develop testicular cancer – a result that might reflect the drug's toxic effects.
"My suspicion is that the effect of cocaine is to kill the germ cells so they're not there," she said, describing how cocaine cuts testicular size and function in mice. "It's more analogous to a mastectomy to reduce the risk of breast cancer. And for a young guy, that would be high price to pay."
Cortessis and Schwartz agree more work is needed to uncover how marijuana use affects testicular cancer risk, but said men "shouldn't assume smoking marijuana has no impact on your health," according to Schwartz.
"I think at this stage of knowledge men deserve to be informed of this," said Cortessis. "It's not a huge body of work, but the results are so consistent that it's very unlikely this is due to chance."