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

36 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

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


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


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