Epidemiologic review of marijuana use and cancer risk

Abstract

Marijuana is the most commonly used illegal drug in the United States and is considered by young adults to be the illicit drug with the least risk. On the other hand, marijuana smoke contains several of the same carcinogens and co-carcinogens as the tar from tobacco, raising concerns that smoking of marijuana may be a risk factor for tobacco-related cancers. We reviewed two cohort studies and 14 case–control studies with assessment of the association of marijuana use and cancer risk. In the cohort studies, increased risks of lung or colorectal cancer due to marijuana smoking were not observed, but increased risks of prostate and cervical cancers among non–tobacco smokers, as well as adult-onset glioma among tobacco and non–tobacco smokers, were observed. The 14 case–control studies included four studies on head and neck cancers, two studies on lung cancer, two studies on non-Hodgkin's lymphoma, one study on anal cancer, one study on penile cancer, and four studies on childhood cancers with assessment of parental exposures. Zhang and colleagues reported that marijuana use may increase risk of head and neck cancers in a hospital-based case–control study in the United States, with dose-response relations for both frequency and duration of use. However, Rosenblatt and co-workers reported no association between oral cancer and marijuana use in a population-based case–control study. An eightfold increase in risk among marijuana users was observed in a lung cancer study in Tunisia. However, there was no assessment of the dose response, and marijuana may have been mixed with tobacco. Parental marijuana use during gestation was associated with increased risks of childhood leukemia, astrocytoma, and rhabdomyosarcoma, but dose-response relations were not assessed. In summary, sufficient studies are not available to adequately evaluate marijuana impact on cancer risk. Several limitations of previous studies include possible underreporting where marijuana use is illegal, small sample sizes, and too few heavy marijuana users in the study sample. Recommendations for future studies are to (1) focus on tobacco-related cancer sites; (2) obtain detailed marijuana exposure assessment, including frequency, duration, and amount of personal use as well as mode of use (smoked in a cigarette, pipe, or bong; taken orally); (3) adjust for tobacco smoking and conduct analyses on nonusers of tobacco; and (4) conduct larger studies, meta-analyses, or pooled analyses to maximize statistical precision and investigate sources of differences in results. Despite the challenges, elucidation of the association between marijuana use and cancer risk is important in weighing the benefits and risks of medical marijuana use and to clarify the impact of marijuana use on public health.

Introduction

Marijuana (cannabis) is the most commonly used illegal drug in the United States, and it is considered by young adults to be the illicit drug with the least risk (Johnston et al., 2003, Johnston et al., 2004). Several lines of evidence support the suggestion that marijuana smoking may be a risk factor for aerodigestive tract cancers:

• Marijuana smoke contains several of the same carcinogens and co-carcinogens as those in tobacco smoke, including vinyl chlorides, phenols, nitrosamines, reactive oxygen species, and various polycyclic aromatic hydrocarbons (PAHs) (Hoffmann et al., 1975).

• Benzo[a]pyrene, a procarcinogenic PAH, is present in marijuana tar at a higher concentration than in tobacco tar (Hoffmann et al., 1975).

• Relative to tobacco smoking, marijuana smoking may involve inhalation of approximately three times the amount of tar and the retention of one third more of the inhaled tar in the respiratory tract (Wu et al., 1988).

• Smoking a few marijuana cigarettes a day has been reported to have similar effects, as observed on histopathologic evaluation of the tracheobronchial epithelium, as those observed with daily smoking of more than 20 tobacco cigarettes (Fligiel et al., 1997, Gong et al., 1987).

• Evaluation of bronchial mucosal biopsy specimens obtained from marijuana smokers without any clinically apparent disease showed more abnormalities than were observed for non–marijuana smokers in molecular markers of dysregulated growth, such as Ki-67 (a proliferation marker), epidermal growth factor receptor, and DNA ploidy (marker of genetic instability) (Barsky et al., 1998).

Other research has focused on the potential therapeutic aspects of marijuana for patients with cancer or with chronic diseases such as multiple sclerosis. For patients with cancer, marijuana has been studied for palliative effects, such as appetite stimulation and relief of pain and nausea and vomiting, as well as for potential antitumor effects such as tumor growth inhibition (Guzman, 2003). The U.S. Food and Drug Administration (FDA) has approved two capsule drugs related to marijuana, dronabinol (Marinol) and nabilone (Cesamet), for treatment of nausea and vomiting due to cancer chemotherapy (Guzman, 2003). Marijuana smoking for medical use is not approved by the FDA, although smoking marijuana for medical purposes has been legalized in several states in the United States.

It is critical to assess whether marijuana use may contribute to cancer causation in human beings because many individuals assume it to be a harmless drug. Because of its use for medical purposes, the notion that it is safe is further propagated. Although smoking of marijuana is presumably the most common form of use (Duffus, 1997), marijuana can also be taken orally, either directly or mixed with food. Data on the prevalence of marijuana use by method of intake do not seem to be widely available. It will be important to examine whether there are differences in cancer risk depending on the way in which marijuana is used. In this article, we review the published epidemiologic studies on marijuana use and cancer and make recommendations for future research directions.