Abstract
Introduction: Because of widespread use, understanding the pulmonary effects of cannabis use is important; but its role independent from tobacco smoking is yet to be elucidated. We used Mendelian randomization (MR) to assess the effect of genetic liability to lifetime cannabis use and cannabis use disorder on pulmonary function and lung cancer. Methods: We used four single nucleotide ...
Abstract
Introduction: Because of widespread use, understanding the pulmonary effects of cannabis use is important; but its role independent from tobacco smoking is yet to be elucidated. We used Mendelian randomization (MR) to assess the effect of genetic liability to lifetime cannabis use and cannabis use disorder on pulmonary function and lung cancer. Methods: We used four single nucleotide polymorphisms associated with lifetime cannabis use (p value <5 x 10-8) from a genome-wide association study (GWAS) of 184,765 individuals of European descent from the International Cannabis Consortium, 23andme, and U.K. Biobank as instrumental variables. Seven single nucleotide poly-morphisms (p value <5 x 10-8) were selected as in-struments for cannabis use disorder from a GWAS meta-analysis of 17,068 European ancestry cases and 357,219 controls of European descent from Psychiatric Genomics Consortium Substance Use Disorders working group, Lundbeck Foundation Initiative for Integrative Psychia-tricResearch, and deCode. To assess lung function, GWAS included 79,055 study participants of the SpiroMeta Con-sortium, and for lung cancer GWAS from the InternationalLung Cancer Consortium contained 29,266 cases and 56,450 controls. Results: MR revealed that genetic liability to lifetime cannabis use was associated with increased risk of squa-mous cell carcinoma (OR = 1.22, 95%, confidence interval = 1.07-1.39, p value = 0.003, q value = 0.025). Pleiotropy-robust methods and positive and negative con-trol analyses did not indicate bias in the primary analysis. Conclusions: The findings of this MR analysis suggest evi-dence for a potential causal association between genetic liability for cannabis use and the risk of squamous cell carcinoma. Triangulating MR and observational studies and addressing orthogonal sources of bias are necessary to confirm this finding. (c) 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.
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