Genetic Risk Can Be Decreased: Quitting Smoking Decreases and Delays Lung Cancer for Smokers With High and Low CHRNA5 Risk Genotypes — A Meta-Analysis

Li Shiun Chen, Timothy Baker, Rayjean J. Hung, Amy Horton, Robert Culverhouse, Sarah Hartz, Nancy Saccone, Iona Cheng, Bo Deng, Younghun Han, Helen M. Hansen, Janet Horsman, Claire Kim, Albert Rosenberger, Katja K. Aben, Angeline S. Andrew, Shen Chih Chang, Kai Uwe Saum, Hendrik Dienemann, Dorothy K. HatsukamiEric O. Johnson, Mala Pande, Margaret R. Wrensch, John McLaughlin, Vidar Skaug, Erik H. van der Heijden, Jason Wampfler, Angela Wenzlaff, Penella Woll, Shanbeh Zienolddiny, Heike Bickeböller, Hermann Brenner, Eric J. Duell, Aage Haugen, Irene Brüske, Lambertus A. Kiemeney, Philip Lazarus, Loic Le Marchand, Geoffrey Liu, Jose Mayordomo, Angela Risch, Ann G. Schwartz, M. Dawn Teare, Xifeng Wu, John K. Wiencke, Ping Yang, Zuo Feng Zhang, Margaret R. Spitz, Christopher I. Amos, Laura J. Bierut

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)219-226
Number of pages8
StatePublished - Sep 1 2016

Bibliographical note

Funding Information:
NELCS : The New England Lung Cancer Study was funded by Grant Number P20RR018787 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH).

Funding Information:
The Resource for Lung Cancer in North Trent (ReSoLUCENT)/Sheffield: This study has been supported by Sheffield ECMC (Experimental Cancer Medicine Centre) and Weston Park Hospital Cancer Charity.

Funding Information:
Mayo Study, Mayo Clinic, College of Medicine: The contribution was supported by NIH-R01–80127/84354 and Mayo Foundation Fund.

Funding Information:
Norway: Funding by the Norwegian Cancer Society and the Norwegian Research Council.

Funding Information:
Tampa, FL: This study was supported by Public Health Service grants P01-CA68384 and R01-DE13158 from the National Institutes of Health.

Funding Information:
Greater Toronto Area Lung Cancer study : This study was supported by Canadian Cancer Society Research Institute (no. 020,214) to R. Hung.

Funding Information:
Netherlands Radboudumc : The study was funded by an investment grant of Radboud university medical center.

Funding Information:
UCLA: This study is supported by the Alper Research Program for Environmental Genomics of the UCLA Jonsson Comprehensive Cancer Center and the National Institute of Health (CA90833, DA11386, CA77954, CA09142, CA96134, and ES 011667).

Funding Information:
Karmanos Cancer Institute, Wayne State University: The Karmanos Cancer Institute contribution was supported by the National Institutes of Health (NIH) (R01CA60691, R01CA87895, N01PC35145, P30CA022453).

Funding Information:
Germany Saarland ESTHER Study. This study was supported in part by the Baden-Württemberg State Ministry of Science, Research and Arts; by the German Federal Ministry of Education and Research.

Funding Information:
LUCY was partly funded by the National Genome Research Network (NGFN), the DFG (BI 576/2-1; BI 576/2–2), the HGF and the Federal office for Radiation Protection (BfS: STSch4454). The Heidelberg sample collection was partly supported by the Deutsche Krebshilfe (70–2919). The KORA platform predominantly is financed by public funds allocated to the Helmholtz Zentrum München by the Federal Ministry of Education and Research and the State of Bavaria. Genotyping was performed in the Genome Analysis Center (GAC) of the Helmholtz Zentrum München.

Funding Information:
Hawaii Case-Control Study : This project was supported by Grant ROI-CA-55874 and Contract NOI-CN-05,223 from the United States National Cancer Institute and by Grant EDT-78 from the American Cancer Society.

Funding Information:
This work was supported in part by grants from the National Institutes of Health (grants ES06717, R01CA52689). The collection of cancer incidence data was supported by the California Department of Public Health as part of the statewide cancer reporting program; the National Cancer Institute's Surveillance, Epidemiology and End Results Program under contract N01-PC-35,136 awarded to the Northern California Cancer Center; and the Centers for Disease Control and Prevention's National Program of Cancer Registries, under agreement #U55/CCR921930-02 awarded to the Public Health Institute.

Publisher Copyright:
© 2016 Forschungsgesellschaft für Arbeitsphysiologie und Arbeitschutz e.V.


  • Genetics
  • Lung cancer
  • Meta-analysis
  • Smoking cessation


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