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Lookup NU author(s): Professor Dawn Teare
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
© 2016 Forschungsgesellschaft für Arbeitsphysiologie und Arbeitschutz e.V. Background Recent meta-analyses show that individuals with high risk variants in CHRNA5 on chromosome 15q25 are likely to develop lung cancer earlier than those with low-risk genotypes. The same high-risk genetic variants also predict nicotine dependence and delayed smoking cessation. It is unclear whether smoking cessation confers the same benefits in terms of lung cancer risk reduction for those who possess CHRNA5 risk variants versus those who do not. Methods Meta-analyses examined the association between smoking cessation and lung cancer risk in 15 studies of individuals with European ancestry who possessed varying rs16969968 genotypes (N = 12,690 ever smokers, including 6988 cases of lung cancer and 5702 controls) in the International Lung Cancer Consortium. Results Smoking cessation (former vs. current smokers) was associated with a lower likelihood of lung cancer (OR = 0.48, 95%CI = 0.30–0.75, p = 0.0015). Among lung cancer patients, smoking cessation was associated with a 7-year delay in median age of lung cancer diagnosis (HR = 0.68, 95%CI = 0.61–0.77, p = 4.9 ∗ 10–10). The CHRNA5 rs16969968 risk genotype (AA) was associated with increased risk and earlier diagnosis for lung cancer, but the beneficial effects of smoking cessation were very similar in those with and without the risk genotype. Conclusion We demonstrate that quitting smoking is highly beneficial in reducing lung cancer risks for smokers regardless of their CHRNA5 rs16969968 genetic risk status. Smokers with high-risk CHRNA5 genotypes, on average, can largely eliminate their elevated genetic risk for lung cancer by quitting smoking- cutting their risk of lung cancer in half and delaying its onset by 7 years for those who develop it. These results: 1) underscore the potential value of smoking cessation for all smokers, 2) suggest that CHRNA5 rs16969968 genotype affects lung cancer diagnosis through its effects on smoking, and 3) have potential value for framing preventive interventions for those who smoke.
Author(s): Chen L-S, Baker T, Hung RJ, Horton A, Culverhouse R, Hartz S, Saccone N, Cheng I, Deng B, Han Y, Hansen HM, Horsman J, Kim C, Rosenberger A, Aben KK, Andrew AS, Chang S-C, Saum K-U, Dienemann H, Hatsukami DK, Johnson EO, Pande M, Wrensch MR, McLaughlin J, Skaug V, van der Heijden EH, Wampfler J, Wenzlaff A, Woll P, Zienolddiny S, Bickeboller H, Brenner H, Duell EJ, Haugen A, Bruske I, Kiemeney LA, Lazarus P, Le Marchand L, Liu G, Mayordomo J, Risch A, Schwartz AG, Teare MD, Wu X, Wiencke JK, Yang P, Zhang Z-F, Spitz MR, Amos CI, Bierut LJ
Publication type: Article
Publication status: Published
Journal: EBioMedicine
Year: 2016
Volume: 11
Pages: 219-226
Print publication date: 01/09/2016
Online publication date: 10/08/2016
Acceptance date: 06/08/2016
Date deposited: 12/11/2019
ISSN (electronic): 2352-3964
Publisher: Elsevier BV
URL: https://doi.org/10.1016/j.ebiom.2016.08.012
DOI: 10.1016/j.ebiom.2016.08.012
PubMed id: 27543155
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