Marijuana use does not appear to be associated with an increased risk of developing oral cancer

Contrary to previous research findings that have suggested a link, marijuana use does not appear to be associated with an increased risk of developing oral cancer, according to a large, population-based study led by researchers at Fred Hutchinson Cancer Research Center.

Their findings, the result of the most comprehensive evaluation to date regarding the association between marijuana use and the incidence of oral squamous-cell carcinoma, appear in the June issue of Cancer Research, a publication of the American Association for Cancer Research.

The study, conducted in collaboration with researchers at the University of Illinois Urbana-Champaign and Seattle's Center for Health Studies, Group Health Cooperative, found no association between marijuana use and increased oral-cancer risk, regardless of how long, how much or how often a person has used marijuana.

The study also found no increased risk among marijuana users who had other underlying risk factors for oral cancer, such as a history of tobacco use or heavy alcohol use. "When asking whether any marijuana use puts you at increased risk of oral cancer, our study is pretty solid in saying there's nothing going on there," said Stephen M. Schwartz, Ph.D., a member of Fred Hutchinson's Public Health Sciences Division and the senior author of the study.

The study also found that marijuana smokers with certain common genetic variations that are known to interfere with the body's detoxification process are at no greater risk of oral cancer than those who carry normal copies of such genes. Specifically, the researchers found that marijuana users with defective versions of GST (gluthathione S-transferase) genes, a class of genes that produce detoxifying enzymes that help whisk toxic byproducts from the body, were at no greater risk of oral cancer than those who carry normal versions of GST.

"Our study isn't the last word on whether there are certain genetic factors that may put people who smoke marijuana at an increased risk of oral cancer, but at least with respect to GST, we didn't find any evidence that marijuana use caused a higher risk than expected in any genetic subgroups," said first author Karin A. Rosenblatt, Ph.D., an associate professor of community health in the College of Applied Life Studies at the University of Illinois at Urbana Champaign.

The study involved 407 oral-cancer cases and 615 healthy control subjects from western Washington who had been interviewed in detail about their history of marijuana use, among other lifestyle factors. Participants, both male and female, ranged in age from 18 to 65. The oral-cancer cases were identified through a population-based cancer registry housed at Fred Hutchinson that is part of the National Cancer Institute's Surveillance, Epidemiology and End Results program. The National Cancer Institute and the National Institute of Dental and Craniofacial Research (both branches of the National Institutes of Health) funded the research.

The Fred Hutchinson study counters findings from a smaller investigation, widely publicized in 1999, which suggested that ever-users of marijuana were at more than twice the risk of getting head-and-neck squamous-cell carcinoma as compared to non-users. "Our study casts a fair bit of doubt on the overall conclusion of the previous study," Schwartz said.

The earlier study had a number of limitations, most importantly the fact that its control, or comparison, group was comprised of individuals who had donated blood at the same hospital where the oral-cancer cases had been treated. "Blood donors tend to have fewer high-risk habits than the general population," Schwartz said, referring to the fact that they're screened for certain lifestyle factors such as intravenous-drug use as well as for previous infection with HIV and hepatitis. Blood donors might therefore be less likely to have a history of marijuana use, he said. "We felt our study, which used controls selected from the general population, could more accurately determine whether oral-cancer patients were more likely to have used marijuana," he said. Another strength of the Fred Hutchinson study is that it involved nearly three times as many participants as the previous investigation, which included 173 oral-cancer cases and 176 healthy controls. "The size of our study tends to make our findings statistically stable," Schwartz said.

In addition, the Fred Hutchinson study collected much more detailed information about the participants' history of marijuana use than did the previous investigation, and it also included a greater proportion of long-term marijuana users; 10.9 percent of participants in the Fred Hutchinson study reported smoking marijuana for five or more years as compared to 3.5 percent of participants in the previous study.

Despite the strengths of the most recent study, Schwartz is quick to point out its limitations. First, like the previous study, it relied on participants' self-reporting of marijuana use, which could have been somewhat biased. Second, only 60 percent if the intended subjects actually participated. "However, those who did participate in the study appeared to be representative of what we'd expect in terms of lifestyle factors associated with oral-cancer epidemiology," Schwartz said. "The oral-cancer patients in our study tended to smoke a lot more, they drank a lot more and they were of lower income and education level than the general population.

In addition, our study's control group echoed national estimates of marijuana use." The study found similar marijuana-use patterns among oral-cancer cases and healthy controls. The majority used marijuana less than once a week, only 1 to 2 percent of cases and controls reported smoking marijuana daily or more, and only 6 percent of cases and 4 percent of controls reported having smoked marijuana for 15 years or more. Because the incidence of extensive, long-term marijuana use was so low among the study population -- a reflection of the population at large -- it is unclear whether extremely heavy use over many years is related to the risk oral cancer, Schwartz said. "Certainly even for moderate levels of use our study is pretty solid in saying there's no association, but when you get out to heavy-use patterns we can't be sure, because the numbers are still too small," said Schwartz, also a professor of epidemiology at the University of Washington School of Public Health and Community Medicine.

National surveys have found that about a quarter of the population has smoked marijuana at some point in their lives, and that about 4 percent of the population, or 6 million people, report occasional use of marijuana. While the incidence of casual marijuana use has remained stable during the past decade, habitual use/abuse appears to be on the rise. Two recent, nationally representative surveys by the National Institute on Drug Abuse found habitual marijuana use/dependence has increased more than 20 percent in the past decade among American adults, particularly young minorities and baby boomers. Such use is defined as repeated use of the drug that causes problems functioning at work, in school or in social situations, or creating marijuana-related legal problems.

According to the American Cancer Society, more than 28,000 new cases of oral cavity/pharynx cancer are expected this year; incidence rates are more than twice as high in men as in women. The five-year survival rate for all stages combined is 57 percent. Fred Hutchinson Cancer Research Center, home of two Nobel laureates, is an independent, nonprofit research institution dedicated to the development and advancement of biomedical technology to eliminate cancer and other potentially fatal diseases.

Fred Hutchinson receives more funding from the National Institutes of Health than any other independent U.S. research center. Recognized internationally for its pioneering work in bone-marrow transplantation, the center's four scientific divisions collaborate to form a unique environment for conducting basic and applied science.

Fred Hutchinson, in collaboration with its clinical and research partners, the University of Washington Academic Medical Center and Children's Hospital and Regional Medical Center, is the only National Cancer Institute-designated comprehensive cancer center in the Pacific Northwest and is one of 38 nationwide. For more information, visit the center's Web site at http://www.fhcrc.org.