Unit of Medical Epidemiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK; MRC Biostatistics Unit, University of Cambridge, Cambridge, UK.
EBioMedicine. 2022 Aug;82:104154. doi: 10.1016/j.ebiom.2022.104154. Epub 2022 Jul 8.
The causal association between cigarette smoking and several diseases remains equivocal. The purpose of this study was to appraise the causal role of smoking in a wide range of diseases by summarizing the evidence from Mendelian randomization (MR) studies.
MR studies on genetic liability to smoking initiation or lifetime smoking (composite of smoking initiation, heaviness, duration, and cessation) in relation to circulatory system, digestive system, nervous system, musculoskeletal system, endocrine, metabolic, and eye diseases, and neoplasms published until February 15, 2022, were identified in PubMed. De novo MR analyses were performed using summary statistics data from genome-wide association studies. Meta-analysis was applied to combine study-specific estimates.
Meta-analyses of findings of 29 published MR studies and 123 de novo MR analyses of 57 distinct primary outcomes showed that genetic liability to smoking (smoking initiation or lifetime smoking) was associated with increased risk of 13 circulatory system diseases, several digestive system diseases (including diverticular, gallstone, gastroesophageal reflux, and Crohn's disease, acute pancreatitis, and periodontitis), epilepsy, certain musculoskeletal system diseases (including fracture, osteoarthritis, and rheumatoid arthritis), endocrine (polycystic ovary syndrome), metabolic (type 2 diabetes) and eye diseases (including age-related macular degeneration and senile cataract) as well as cancers of the lung, head and neck, esophagus, pancreas, bladder, kidney, cervix, and ovaries, and myeloid leukemia. Smoking liability was associated with decreased risk of Parkinson's disease and prostate cancer.
This study found robust evidence that cigarette smoking causes a wide range of diseases.
This work was supported by research grants from the Swedish Cancer Society (Cancerfonden), the Swedish Heart Lung Foundation (Hjärt-Lungfonden, 20210351), the Swedish Research Council for Health, Working Life and Welfare (Forte, 2018-00123), and the Swedish Research Council (Vetenskapsrådet, 2019-00977). Stephen Burgess is supported by Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (204623/Z/16/Z) and the National Institute for Health Research Cambridge Biomedical Research Centre (BRC-1215-20014). The views expressed are those of the authors and not necessarily those of the National Institute for Health Research or the Department of Health and Social Care.
吸烟与多种疾病之间的因果关联仍存在争议。本研究旨在通过汇总孟德尔随机化（MR）研究的证据，评估吸烟在广泛疾病中的因果作用。
检索 2022 年 2 月 15 日之前在 PubMed 上发表的关于遗传易感性与吸烟起始或终生吸烟（吸烟起始、吸烟量、吸烟持续时间和戒烟的综合指标）与循环系统、消化系统、神经系统、肌肉骨骼系统、内分泌、代谢和眼部疾病以及肿瘤的 MR 研究。使用来自全基因组关联研究的汇总统计数据进行新的 MR 分析。应用荟萃分析合并研究特异性估计值。
对 29 项已发表的 MR 研究和 123 项针对 57 种不同主要结局的新的 MR 分析的荟萃分析表明，遗传易感性（吸烟起始或终生吸烟）与 13 种循环系统疾病、几种消化系统疾病（包括憩室病、胆石症、胃食管反流病和克罗恩病、急性胰腺炎和牙周炎）、癫痫、某些肌肉骨骼系统疾病（包括骨折、骨关节炎和类风湿性关节炎）、内分泌（多囊卵巢综合征）、代谢（2 型糖尿病）和眼部疾病（包括年龄相关性黄斑变性和老年性白内障）以及肺癌、头颈部癌、食管癌、胰腺癌、膀胱癌、肾癌、宫颈癌和卵巢癌以及骨髓性白血病的风险增加相关。吸烟易感性与帕金森病和前列腺癌的风险降低相关。
本研究发现了强有力的证据表明，吸烟会导致广泛的疾病。
这项工作得到了瑞典癌症协会（Cancerfonden）、瑞典心肺基金会（Hjärt-Lungfonden，20210351）、瑞典研究理事会健康、工作生活和福利部（Forte，2018-00123）和瑞典研究理事会（Vetenskapsrådet，2019-00977）的研究资助。Stephen Burgess 受到了 Wellcome Trust 和英国皇家学会联合资助的 Henry Dale 研究员奖（204623/Z/16/Z）以及英国国立卫生研究院剑桥生物医学研究中心（BRC-1215-20014）的支持。本文观点仅代表作者，不一定代表英国国立卫生研究院或英国卫生部的观点。
