Causal relationship between cannabis use and cancer: a genetically informed perspective.

Purpose: Cannabis use is increasing legally worldwide, while its impact on cancer risk is unclear. This study was performed to investigate the relationship between cannabis use and the risk of several types of cancer. Methods: We conducted a two-sample Mendelian randomization (MR) study to explore the causality of cannabis use on 9 site-specific types of cancer including breast cancer, cervical cancer, melanoma, colorectal cancer, laryngeal cancer, oral cancer, oropharyngeal cancer, esophageal cancer, and glioma. Genome-wide significant genetic instruments (P < 5E-06) for cannabis use were extracted from a large-scale genome-wide association meta-analysis of European ancestry, whereas cancer genetic instruments were extracted from the UK Biobank (UKB) cohort and GliomaScan consortium in the OpenGWAS database. The inverse-variance weighted (IVW) was considered the main method for MR analysis, and sensitivity analyses including MR-Egger, weighted median, MR pleiotropy residual sum, and outlier test (MR-PRESSO) were conducted to evaluate the robustness of the results. Results: Cannabis use was a significant promoting factor for cervical cancer (OR = 1.001265, 95% CI 1.000375-1.002155, P = 0.0053). And we also detected suggestive evidence of the causality of cannabis use on laryngeal cancer (OR = 1.000350, 95% CI 1.000027-1.000672, P = 0.0336) and breast cancer (OR = 1.003741, 95% CI 1.000052-1.007442, P = 0.0467). No evidence of a causal association of cannabis use with other site-specific types of cancer was detected. Additionally, no pleiotropy or heterogeneity was found in the sensitivity analysis. Conclusion: This study indicates a causative association of cannabis use on cervical cancer, while cannabis use may increase the odds of breast cancer and laryngeal cancer, which require further evaluation in large-scale population-based studies.