Chronic Pot Use Possibly Linked to Testicular Cancer

But meta-analysis finds association less clear for other cancers

by Christina Bennett

Chronic marijuana smoking may be linked to the development of testicular germ cell tumor (TGCT), specifically of the nonseminoma histologic subtype, a systematic review and meta-analysis found.

But the evidence was considered low strength because it was based on a pooled analysis of three case-control studies that had a moderate risk of bias, Deborah Korenstein, MD, of Memorial Sloan Kettering Cancer Center in New York City, and colleagues reported in JAMA Network Open.

Their pooled analysis revealed that exposure to a minimum of 1 joint per day for 1 year -- also known as "ever use" -- was not significantly associated with TGCT (OR 1.11, 95% CI 0.81-1.53; I²=48%). Yet, more than 10 years of marijuana use, which was not reported in joint-years, was (OR 1.36, 95% CI 1.03-1.81; I²=0%).

A subgroup analysis further revealed that of the two major histologic types that comprise TGCT, over 10 years of marijuana use was only significantly associated with nonseminoma TGCT (OR 1.85, 95% CI 1.10-3.11; I²=0%).

"I agree that the summary of the three testis cancer studies show that the evidence is of low strength," Leslie Bernstein, PhD, of the Division of Biomarkers of Early Detection and Prevention at City of Hope in Duarte, California, told MedPage Today.

A principle investigator on one of the three testis cancer studies, Bernstein said that one of the issues that concerned her when designing and conducting that study was underreporting the cases' and controls' exposure to marijuana due to it -- as well as nearly all of the other recreational drugs evaluated in the study -- being an illegal substance. "We buried cocaine and marijuana within the list of the other recreational drugs in the hope that we might have honest reporting."

Bernstein said the other two studies had "shortcomings" similar to her group's and believes that the evidence is "suggestive" of an association that should be examined in a well-designed and sufficiently-powered study.

"We cannot yet conclude that chronic marijuana use increases risk of TGCT," she said.

Including a total of 25 studies published from January 1973 to April 2019, the systematic review and meta-analysis also evaluated other cancer types, such as head and neck, oral, and lung, but the findings were even less clear due to limitations, such as flaws in the study methodology and inadequate adjustment for confounders.

A total of eight studies evaluated the risk of lung cancer, all of which had a moderate to high risk of bias, and the results were mixed, leading the study authors to conclude that the evidence of an association between marijuana use and lung cancer was "insufficient."

As for head and neck cancers, four studies evaluated risk of head and neck squamous cell carcinoma, one of which had a low risk of bias and the rest moderate risk, and ever users of marijuana had a similar risk for head and neck squamous cell carcinoma as nonsmokers did (OR 1.26, 95% CI 0.88-1.80; I²=55%). Another four studies evaluated risk of oral cancer, all of which had a moderate to high risk of bias, revealing no evidence of an association between ever use of marijuana and oral cancer.

In addition, studies evaluated risk of prostate cancer, bladder cancer, malignant primary adult-onset glioma, breast cancer, colorectal cancer, and melanoma, and still no sufficient evidence of associations were found with marijuana use.

Except for TGCT, the study authors concluded that the evidence of associations between marijuana use and cancer was "insufficient" and that large-scale longitudinal studies are needed. However, this approach may not be the best, according to Bernstein.

"Assessing exposure in a cohort over time with sufficiently long follow-up to obtain a sufficient number of cancer cases is difficult and I would not suggest starting any new studies," she said. She explained that doing such cohort studies would require convincing current cohort study lead investigators to add valid questions on marijuana "immediately" and to include these questions in most subsequent questionnaires. "A potential problem in cohort studies is the constant fight for space on the questionnaire for such detailed questions."

For testicular cancer, she recommended conducting a large case-control study of young men with testicular cancer to serve as cases and similarly age-, race- and residence-matched healthy men to serve as controls, and that neither cases nor controls should have ever smoked cigarettes.

The study was funded by grants from the National Heart, Lung, and Blood Institute of the National Institutes of Health and the National Cancer Institute.

Korenstein disclosed grant funding from the National Cancer Institute while conducting the study and that her spouse has relationships with industry. One co-author reported grant funding from the National Institutes of Health while conducting the study.

Bernstein reported having no relevant conflicts of interest.