Scoping Review and Meta-Analysis Suggests that Use May Reduce Cancer Risk in the United States.

smoke contains carcinogens similar to tobacco, in addition to compounds with antitumor activity. use reduces the risk of obesity and cannabinoids inhibit chronic inflammation, known causes of cancer. The net effect of use on cancer risk is not known. To examine the association between use and cancer risk in the United States. Identify and analyze published data on cancer risk in users. A total of 55 data points, consisting of risk ratios of cancer in users and nonusers, were identified from 34 studies. Of these, 5 did not contain data essential for inclusion in the meta-analysis. The remaining data showed a nonsignificant trend to an association with reduced risk (relative risk [RR]=0.90, >0.06, =50) although heterogeneity is high (=72.4%). Removal of data with high risk of selection bias (defined as those from North Africa and those that failed to adjust for tobacco) and data with high risk of performance bias (defined as those with fewer than 20 cases or controls among users) resulted in an RR <1.0 (RR=0.86, <0.017, =24) and large effect size (Hedges =0.66), but did not decrease heterogeneity (=74.9). Of all cancer sites, only testicular cancer showed an RR value >1, although this was not significant and had a negligible effect size (RR=1.12, =0.3, Hedges =0.02). Following removal of testicular cancers the remaining data showed a decrease in risk (RR=0.87, <0.025, =41). Cancers of the head and neck showed a negative association with cancer risk (RR=0.83, <0.05), with a large effect size (Hedges =0.55), but high heterogeneity (=79.2%). RR did not reach statistical significance in the remaining cancer site categories (lung, testicular, obesity-associated, other). The data are consistent with a negative association between use and nontesticular cancer, but there is low confidence in this result due to high heterogeneity and a paucity of data for many cancer types.