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Testicular Cancer Risk Increased in Marijuana Users

Medscape
11 February 2009
By Zosia Chustecka

An association between the use of marijuana and an increased risk for testicular cancer, in particular the most aggressive nonseminoma type of the disease, has been reported in paper published online February 9 in Cancer.

The risk for testicular cancer increased by 70% in men who reported current marijuana use, and increased even more in those who smoked marijuana at least weekly and/or had long–term exposure to the drug, starting in adolescence.

“Our study is the first inkling that marijuana use may be associated with testicular cancer,” said senior author Stephen Schwartz, MPH, PhD, epidemiologist at the Fred Hutchinson Cancer Research Center, in Seattle, Washington. However, he noted that there are still many unanswered questions, including why the increased risk is seen in only 1 type of testicular cancer.

The finding is interesting and statistically significant, but the confidence intervals (CI) are fairly large, and this study is not conclusive, said Len Lichtenfeld, MD, deputy chief medical officer at the American Cancer Society. “It does not prove a causal relationship,” he told Medscape Oncology in an interview.

Increase in Incidence Over Past Few Decades
The incidence of testicular cancer has been increasing by around 3% to 6% each year since the 1950s in countries such as the United States, Canada, Europe, Australia, and New Zealand, the researchers note.

Over the same time period, there has been an increase in the use of marijuana in North America, Europe, and Australia. Because chronic marijuana use has multiple adverse effects on the endocrine and reproductive health systems, the researchers wondered whether it could be related to the increase seen in testicular cancer rates.

To test the hypothesis, researchers conducted a population–based case–control study of 369 men with testicular cancer (aged 18–44 years) and 979 age–matched controls. Information on marijuana use, cigarette smoking, and alcohol use was collected from interviews, which were conducted in person.

However, the researchers point out that one of the limitations of their study is that these interviews were actually conducted in only 67.5% of the eligible cases and in 52.2% of the eligible controls. In addition, they had to rely on self–reporting, and “patients with cancer may be expected to more accurately admit to the use of an illegal substance than individuals in a control group,” the researchers comment.

The results must be interpreted in light of these limitations, they caution.

Risk of Cancer Increased by 70%
Current marijuana use was associated with a 70% increased risk for testicular cancer (odds ratio [OR], 1.7; 95% CI, 1.1–2.5). The risk was particularly elevated for current use that was at least weekly (OR, 3.0) or that began in adolescence (OR, 2.8 for boys who were younger than 18 when they started).

These associations were independent of known risk factors for testicular cancer, such as a first–degree family history and a history of undescended testes.

“In addition, all of the associations we observed appeared to be limited to nonseminoma/mixed histologies,” the researchers report.

Why this should be the case is unclear. “Our original hypothesis sought an increasing exposure that would be associated with the risk of all histologic types of testicular cancer,” they write.

Particularly Vulnerable at Puberty?
One of the potential explanations for the association rests on the theory that puberty presents a “window of vulnerability,” during which environmental factors increase the risk for testicular cancer. The disease is thought to arise from primitive germ cells that fail to develop properly and become vulnerable to malignancy, especially during the hormonal surges of puberty.

“Just as the changing hormonal environment of adolescence and adulthood can trigger undifferentiated fetal germ cells to become cancerous, it has been suggested that puberty is a ‘window of opportunity,’ during which lifestyle or environmental factors also can increase the risk of testicular cancer,” commented first author Janet Daling, PhD, also an epidemiologist at the Fred Hutchinson Cancer Research Center.

“This is consistent with the study’s findings that the elevated risk of nonseminoma–type testicular cancer, in particular, was associated with marijuana use prior to age 18,” she said in a statement.

“However, none of these explanations likely would be specific to nonseminomas,” the researchers note.

One of the most intriguing things about this study, from a human interest point of view, is the reason the researchers decided to look for an association between testicular cancer and the use of marijuana, commented Dr. Lichtenfeld.

According to a press release issued by the Fred Hutchinson center, the idea was conceived by Dr. Daling after she heard a lecture 8 years ago that highlighted the fact that the brain and the testes were the only 2 organs in the body found to have receptors for tetrahydrocannabinol (THC), the main psychoactive component of marijuana. However, since then, these receptors have been found in the heart, uterus, spleen, and certain immune system cells.

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