期刊
JOURNAL OF INTERNAL MEDICINE
卷 279, 期 4, 页码 388-398出版社
WILEY
DOI: 10.1111/joim.12454
关键词
CHRNA; COPD; epidemiology; smoking genetics; tobacco-related cancer
资金
- European Research Council [StG-282255]
- Swedish Heart and Lung Foundation
- Swedish Research Council
- Novo Nordisk Foundation
- Skane University Hospital
- Medical Faculty of Lund University
- National Health Services
- Albert Pahlsson Research Foundation
- Region Skane
- King Gustaf V and Queen Victoria Foundation
- Marianne and Marcus Wallenberg Foundation
BackgroundGenetic variation in the cluster on chromosome 15, encoding the nicotinic acetylcholine receptor subunits (CHRNA5-CHRNA3-CHRNB4), has shown strong associations with tobacco consumption and an additional risk increase in smoking-related diseases such as chronic obstructive pulmonary disease (COPD), peripheral artery disease and lung cancer. ObjectivesTo test whether rs1051730 (C/T), a tag for multiple variants in the CHRNA5-CHRNA3-CHRNB3 cluster, is associated with a change in risk of smoking-related mortality and morbidity in the Malmo Diet and Cancer study, a population-based prospective cohort study. MethodsAt baseline participants were classified as current (n = 6951), previous (n = 8426) or never (n = 9417) smokers. Cox-proportional hazards models were used to determine the correlation between rs1051730 and incidence of first COPD, tobacco-related cancer, other cancer and cardiovascular disease (CVD), and total mortality due to these causes, during approximately 14 years of follow-up. ResultsAmongst current smokers there were 480 first incident COPD events, 852 tobacco-related cancers, 810 other cancers and 1022 CVD events. A total of 1508 deaths occurred, including 500 due to CVD, 102 due to respiratory diseases and 677 due to cancer. In adjusted additive models, an increasing number of T alleles were associated with a gradual increase in total mortality, incident COPD and tobacco-related cancer, even after adjustment for smoking quantity. No significant associations were observed amongst never smokers. ConclusionOur data suggest that gene variance in the CHRNA5-CHRNA3-CHRNB4 cluster is associated with an increased risk of death, incidence of COPD and tobacco-related cancer in smokers. These findings indicate an individual susceptibility to tobacco use and its complications; this may be important when targeting and designing smoking cessation therapies.
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