Nicotinic Acetylcholine Receptor Polymorphism, Smoking Behavior, and Tobacco-Related Cancer and Lung and Cardiovascular Diseases: A Cohort Study
Nicotinic Acetylcholine Receptor Polymorphism, Smoking Behavior, and Tobacco-Related Cancer and Lung and Cardiovascular Diseases: A Cohort Study
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DOI：
10.1200/jco.2010.32.9870
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发表时间：
2011-07-20
影响因子：
45.3
通讯作者：
Nordestgaard, Borge G.
中科院分区：
文献类型：
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作者：
Kaur-Knudsen, Diljit;Bojesen, Stig E.;Nordestgaard, Borge G.
目的探讨普通人群中标记CHRNA3-CHRNB4-CHRNA5基因簇的15q25染色体上烟碱乙酰胆碱受体多态性（rs1051730）与吸烟行为、烟草相关癌症、肺部和心血管疾病的关系。方法来自哥本哈根城市心脏研究的一千三百三十名参与者进行了基因分型，并进行了长达18年的100%完全随访。吸烟行为在基线时进行测量。终点是肺癌、膀胱癌、慢性阻塞性肺疾病、缺血性心脏病和缺血性中风。多因素调整和基因型调整的累积烟草消费超过40包年与0包年的亚危险比肺癌为32.5 (95% CI, 12.0 ~ 87.7)，膀胱癌为2.2 (95% CI, 1.1 ~ 4.5)，慢性阻塞性肺病为9.4 (95% CI, 6.9 ~ 12.7)，缺血性心脏病为1.5 (95% CI, 1.3 ~ 1.8)，缺血性中风为1.1 （95% CI, 0.8 ~ 1.4）。吸烟非携带者和纯合子每日烟草消费量分别为16和18 g/d (P < 0.001)，累积烟草消费量分别为28和31包年（P = 0.003），吸烟吸入量分别为71.9%和78.1% （P < 0.001）。肺癌纯合子与非携带者的多因素校正和吸烟行为校正亚危险比为1.6 (95% CI, 1.1 - 2.2)，膀胱癌为1.7 (95% CI, 1.0 - 3.0)，慢性阻塞性肺疾病为1.3 (95% CI, 1.1 - 1.6)，缺血性心脏病为0.9 (95% CI, 0.7 - 1.0)，缺血性中风为1.1 （95% CI, 0.8 - 1.4）。结论虽然吸烟与一般人群的主要烟草相关疾病有关，但尼古丁乙酰胆碱受体多态性与调整吸烟后肺癌、膀胱癌和慢性阻塞性肺疾病的额外风险增加有关。[J]中华临床杂志，29(2):775 - 782。(C) 2011年美国临床肿瘤学会
PurposeWe examined the associations between the nicotinic acetylcholine receptor polymorphism (rs1051730) on chromosome 15q25 marking the gene cluster CHRNA3-CHRNB4-CHRNA5, smoking behavior, and tobacco-related cancer and lung and cardiovascular diseases in the general population.MethodsTen thousand three hundred thirty participants from the Copenhagen City Heart Study were genotyped and observed prospectively with up to 18 years of 100% complete follow-up. Smoking behavior was measured at baseline. End points were lung cancer, bladder cancer, chronic obstructive pulmonary disease, ischemic heart disease, and ischemic stroke.ResultsMultifactorially adjusted and genotype-adjusted subhazard ratios for a cumulative tobacco consumption above 40 pack-years versus 0 pack-years were 32.5 (95% CI, 12.0 to 87.7) for lung cancer, 2.2 (95% CI, 1.1 to 4.5) for bladder cancer, 9.4 (95% CI, 6.9 to 12.7) for chronic obstructive pulmonary disease, 1.5 (95% CI, 1.3 to 1.8) for ischemic heart disease, and 1.1 (95% CI, 0.8 to 1.4) for ischemic stroke. Among smoking noncarriers and homozygotes, daily tobacco consumption was 16 and 18 g/d (P < .001), cumulative tobacco consumption was 28 and 31 pack-years (P = .003), and smoking inhalation was 71.9% and 78.1% (P < .001), respectively. Multifactorially adjusted and smoking behavior-adjusted subhazard ratios for homozygotes versus noncarriers were 1.6 (95% CI, 1.1 to 2.2) for lung cancer, 1.7 (95% CI, 1.0 to 3.0) for bladder cancer, 1.3 (95% CI, 1.1 to 1.6) for chronic obstructive pulmonary disease, 0.9 (95% CI, 0.7 to 1.0) for ischemic heart disease, and 1.1 (95% CI, 0.8 to 1.4) for ischemic stroke.ConclusionAlthough smoking is associated with major tobacco-related diseases in the general population, the nicotinic acetylcholine receptor polymorphism is associated with additional increased risk of lung cancer, bladder cancer, and chronic obstructive pulmonary disease after adjustment for smoking. J Clin Oncol 29:2875-2882. (C) 2011 by American Society of Clinical Oncology