Association Between Marijuana Use and Risk of Cancer. A Systematic Review and Meta-analysis
Mehrnaz Ghasemiesfe, Brooke Barrow, Samuel Leonard, Salomeh Keyhani, Deborah Korenstein,
JAMA Network Open, 2019, 2, (11), e1916318.
doi : 10.1001/jamanetworkopen.2019.16318
IMPORTANCE : Marijuana use is common and growing in the United States amid a trend toward
legalization. Exposure to tobacco smoke is a well-described preventable cause of many cancers; the
association of marijuana use with the development of cancer is not clear.
OBJECTIVE : To assess the association of marijuana use with cancer development.
DATA SOURCES : A search of PubMed, Embase, PsycINFO, MEDLINE, and the Cochrane Library was
conducted on June 11, 2018, and updated on April 30, 2019. A systematic review and meta-analysis of studies published from January 1, 1973, to April 30, 2019, and references of included studies were performed, with data analyzed from January 2 through October 4, 2019.
STUDY SELECTION : English-language studies involving adult marijuana users and reporting cancer
development. The search strategy contained the following 2 concepts linked together with the AND
operator: marijuana OR marihuana OR tetrahydrocannabinol OR cannabinoid OR cannabis; AND
cancer OR malignancy OR carcinoma OR tumor OR neoplasm.
DATA EXTRACTION AND SYNTHESIS : Two reviewers independently reviewed titles, abstracts, and full-text articles; 3 reviewers independently assessed study characteristics and graded evidence
strength by consensus.
MAIN OUTCOMES AND MEASURES : Rates of cancer in marijuana users, with ever use defined as at least 1 joint-year exposure (equivalent to 1 joint per day for 1 year), compared with nonusers. Metaanalysis was conducted if there were at least 2 studies of the same design addressing the same cancer without high risk of bias when heterogeneitywas lowto moderate for the following 4 cancers: lung, head and neck squamous cell carcinoma, oral squamous cell carcinoma, and testicular germ cell tumor (TGCT), with comparisons expressed as odds ratios (ORs) with 95%CIs.
RESULTS : Twenty-five English-language studies (19 case-control, 5 cohort, and 1 cross-sectional) were included; few studies (n = 2) were at low risk of bias. In pooled analysis of case-control studies, ever use of marijuanawas not associated with head and neck squamous cell carcinoma or oral cancer. In pooled analysis of 3 case-control studies, more than 10 years of marijuana use (joint-years not reported) was associated with TGCT (OR, 1.36; 95%CI, 1.03-1.81; P = .03; I2 = 0%) and nonseminoma TGCT (OR, 1.85; 95%CI, 1.10-3.11; P = .04; I2 = 0%). Evaluations of ever use generally found no association with cancers, but exposure levels were low and poorly defined. Findings for lung cancer were mixed, confounded by few marijuana-only smokers, poor exposure assessment, and inadequate adjustment; meta-analysis was not performed for several outcomes.
CONCLUSIONS AND RELEVANCE : Low-strength evidence suggests that smoking marijuana is associated with developing TGCT; its association with other cancers and the consequences of higher levels of use are unclear. Long-term studies in marijuana-only smokers would improve understanding
of marijuana’s association with lung, oral, and other cancers.
TRIAL REGISTRATION PROSPERO : identifier: CRD42018102457
Question : What is the association between marijuana use and cancer development in adults with at least 1 joint-year exposure (equivalent to 1 joint per day for 1 year)?
Findings : This systematic review and meta-analysis identified 25 Englishlanguage studies assessing marijuana use and the risk for developing lung, head and neck, urogenital, and other cancers. In meta-analyses, regular marijuana use was associated with development of testicular germ cell tumors, although the strength of evidence was low; evidence regarding other cancers was insufficient.
Meaning : Sustained marijuana use may increase the risk for testicular cancer, but overall, the association of marijuana use and cancer development remains unclear.
Marijuana is the most widely used illicit substance in the United States, with almost half of adults reporting lifetime use.1 Rates are increasing,2 with use among young adults (age range, 18-29 years) doubling from 10.5%in 2002 to 21.2%in 2014. Smoking remains the main route of marijuana exposure.3,4
Marijuana smoke and tobacco smoke share carcinogens, including toxic gases, reactive oxygen species, and polycyclic aromatic hydrocarbons, such as benzo[α]pyrene and phenols,5 which are 20 times higher in unfiltered marijuana than in cigarette smoke.6 The larger the puff volume, the greater the depth of inhalation,7 and longer breath-holding time with marijuana compared with cigarette smoking leads to higher tar and carbon monoxide exposure.8 Furthermore, marijuana use is associated with histopathologic bronchial inflammatory changes comparable to changes observed with smoking tobacco.9 Given that cancer is the second leading cause of death in the United States10 and smoking remains the largest preventable cause of cancer death (responsible for 28.6%of all cancer deaths in 2014),11 similar toxic effects of marijuana smoke and tobacco smokemay have important health implications.
Aside from shared properties with tobacco, marijuana use may alter cancer risk through other mechanisms. Tetrahydrocannabinol, the primary psychoactive ingredient in marijuana, may have adverse immunomodulatory effects8,9 associated with cancer. Two proto-oncogenes are overexpressed in the bronchial epithelium of marijuana-only smokers, with a higher frequency of gene expression compared with tobacco-only smokers.8,12 In contrast, cannabinoids, including tetrahydrocannabinol, can inhibit proliferation of some cancer cell types, impede angiogenesis in vitro, and reduce cancer growth in some animal models.13,14 The net association of marijuana use with developing cancer is unclear.
The increasing prevalence of marijuana use, particularly among young adults, raises concerns regarding whether using marijuana increases the risk for developing cancer. Despite increasing social acceptance of marijuana use, there remains a dearth of information on the association between marijuana consumption and health, including its association with incident cancer.We conducted a systematic review and meta-analysis to improve the understanding of the association of marijuana use with developing cancers.