No Link Between Marijuana Use and Cancer, Except TGCT

Nick Mulcahy

November 27, 2019

More than 10 years of marijuana use is associated with the development of testicular germ cell tumor (TGCT), but the quality of the evidence is "low strength" and there is insufficient evidence to support an association between ever having used marijuana and other types of cancer.

These are the conclusions from a new systematic review and meta-analysis published online today in JAMA Open Network.

Lead author Mehrnaz Ghasemiesfe, MD, Northern California Institute of Research and Education, San Francisco, and colleagues explain that they wondered if marijuana smoke might cause cancer, because tobacco smoke does. Once burned, the two substances share carcinogens, including toxic gases, reactive oxygen species, and polycyclic aromatic hydrocarbons like benzo[α]pyrene and phenols.

So the investigators looked at studies from 1973 to 2018 comparing nonusers to marijuana ever-users, who were defined as using one joint per day for 1 year.

The team found 25 English-language studies (19 case-control, 5 cohort, and 1 cross-sectional). But only two studies were "low risk of bias."

In pooled analysis of case-control studies, ever-use of marijuana was not associated with two obvious cancer types: either head and neck squamous cell carcinoma or oral cancer.

But in pooled analysis of three case-control studies, more than 10 years of marijuana use was associated with TGCT (odds ratio [OR], 1.36; 95% confidence interval [CI], 1.03 - 1.81; P = .03) and nonseminoma TGCT (OR, 1.85; 95% CI, 1.10 - 3.11; P = .04).

The quality of the evidence was not high in any study.

For example, evaluations of ever-use generally found no association with cancers, but exposure levels were "low and poorly defined," said the authors. Also, findings for lung cancer studies were mixed, "confounded by few marijuana-only smokers, poor exposure assessment, and inadequate adjustment."

The authors believe that long-term studies in marijuana-only smokers "would improve understanding of marijuana's association with lung, oral, and other cancers."

Previous systematic reviews in this area have looked at multiple cancers, but examined them individually.

For example, there are two systematic reviews looking at the association between smoking marijuana and lung cancer. One looked at biological plausibility (ie, molecular, cytomorphologic, and histopathologic changes); the second study examined pulmonary toxic effects and found mixed evidence of an association with lung cancer (but did not pool data to estimate an overall association).

"Our findings are notable in a time of increasing marijuana use in the United States, with novel drug delivery methods, including vaping and edibles, becoming more popular, particularly in states that have legalized recreational use and among adolescents," the authors comment.

However, most of the studies included in their review are not recent, an important fact because, in the past, marijuana "smoking was the near-universal form of exposure," the authors note. Vaped marijuana is believed to have fewer long-term toxic effects than smoked marijuana.

Until more is known about any carcinogenicity of marijuana, "clinicians should discuss marijuana use with patients to raise awareness of the lack of clarity on potential clinically important harms and to debunk beliefs in unproven benefits," say the authors.

The study was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health. Study author Deborah Korenstein's work was supported in part by the National Cancer Institute.

JAMA Network Open. Published online November 27, 2019. Full text

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