Department of Epidemiology, Ludwig-Maximilian University of Munich, University Center for Health Sciences at the Klinikum (UNIKA-T) Augsburg, Augsburg, Germany; Independent Research Group Clinical Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich, Germany; Institute of Health Services Research in Dentistry, University of Münster, Münster, Germany.
Department of Epidemiology and Preventive Medicine, University of Regensburg, Germany.
J Thorac Oncol. 2021 Jul;16(7):1127-1135. doi: 10.1016/j.jtho.2021.03.025. Epub 2021 Apr 20.
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.
We used four single nucleotide polymorphisms associated with lifetime cannabis use (p value <5 × 10) 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 polymorphisms (p value <5 × 10) were selected as instruments 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 PsychiatricResearch, and deCode. To assess lung function, GWAS included 79,055 study participants of the SpiroMeta Consortium, and for lung cancer GWAS from the International Lung Cancer Consortium contained 29,266 cases and 56,450 controls.
MR revealed that genetic liability to lifetime cannabis use was associated with increased risk of squamous 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 control analyses did not indicate bias in the primary analysis.
The findings of this MR analysis suggest evidence 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.
由于大麻的广泛使用，了解其对肺部的影响很重要；但其独立于吸烟的作用仍有待阐明。我们使用孟德尔随机化（MR）来评估终生大麻使用和大麻使用障碍的遗传易感性对肺功能和肺癌的影响。
我们使用来自国际大麻联合会、23andMe 和英国生物银行的欧洲血统的 184765 名个体的全基因组关联研究（GWAS）中的四个与终生大麻使用相关的单核苷酸多态性（p 值 <5×10）作为工具变量。从精神疾病基因组学联盟物质使用障碍工作组、Lundbeck 基金会综合精神病学研究倡议和 deCode 的欧洲血统的 17068 例病例和 357219 例对照的 GWAS 荟萃分析中，选择了七个与大麻使用障碍相关的单核苷酸多态性（p 值 <5×10）作为工具。为了评估肺功能，GWAS 包括了 SpiroMeta 联合会的 79055 名研究参与者，而国际肺癌联合会的肺癌 GWAS 则包含了 29266 例病例和 56450 例对照。
MR 显示，终生大麻使用的遗传易感性与鳞状细胞癌的风险增加相关（OR=1.22，95%置信区间 1.07-1.39，p 值=0.003，q 值=0.025）。稳健的多效性方法和阳性和阴性对照分析表明，主要分析中没有偏差。
这项 MR 分析的结果表明，大麻使用的遗传易感性与鳞状细胞癌的风险之间存在潜在的因果关系。通过 MR 和观察性研究的三角测量，并解决正交的偏倚来源，有必要证实这一发现。
