EBioMedicine (Sep 2016)
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. Hatsukami,
- Eric 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
Affiliations
- Li-Shiun Chen
- Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA
- Timothy Baker
- Tobacco Research and Intervention, University of Wisconsin, School of Medicine, Madison, WI, USA
- Rayjean J. Hung
- Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada
- Amy Horton
- Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA
- Robert Culverhouse
- Department of Medicine, Washington University School of Medicine, St. Louis, MO
- Sarah Hartz
- Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA
- Nancy Saccone
- Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA
- Iona Cheng
- Cancer Prevention Institute of California, Fremont, CA, USA
- Bo Deng
- Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA
- Younghun Han
- Department of Community and Family Medicine, Geisel School of Medicine at Dartmouth, Hanover, NH, USA
- Helen M. Hansen
- Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA
- Janet Horsman
- Department of Oncology, University of Sheffield, Sheffield, UK
- Claire Kim
- Department of Epidemiology, UCLA Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA, USA
- Albert Rosenberger
- Department of Genetic Epidemiology, University of Goettingen Medical School, Goettingen, Germany
- Katja K. Aben
- Netherlands Comprehensive Cancer Organization, Utrecht, The Netherlands & Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands
- Angeline S. Andrew
- Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA
- Shen-Chih Chang
- Department of Epidemiology, UCLA Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA, USA
- Kai-Uwe Saum
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Hendrik Dienemann
- Department of Thoracic Surgery, Thoraxklinik at University Hospital Heidelberg, Heidelberg, Germany
- Dorothy K. Hatsukami
- Department of Psychiatry, University of Minnesota, Minneapolis, MN, USA
- Eric O. Johnson
- Division of Health, Social and Economic Research, Research Triangle Institute, International, Research Triangle Park, NC 27709, USA
- Mala Pande
- Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Margaret R. Wrensch
- Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA
- John McLaughlin
- Public Health Ontario, Toronto, Canada
- Vidar Skaug
- Department of Biological and Chemical Work Environment, National Institute of Occupational Health, Oslo, Norway
- Erik H. van der Heijden
- Department for Lung Diseases, Radboud University Medical Centre, Radboud Institute for Health Sciences, Nijmegen, The Netherlands
- Jason Wampfler
- Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA
- Angela Wenzlaff
- Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA
- Penella Woll
- Department of Oncology, University of Sheffield, Sheffield, UK
- Shanbeh Zienolddiny
- Department of Biological and Chemical Work Environment, National Institute of Occupational Health, Oslo, Norway
- Heike Bickeböller
- Department of Genetic Epidemiology, University of Goettingen Medical School, Goettingen, Germany
- Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Eric J. Duell
- Unit of Nutrition, Environment and Cancer, Epidemiology Program, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain
- Aage Haugen
- Department of Biological and Chemical Work Environment, National Institute of Occupational Health, Oslo, Norway
- Irene Brüske
- Helmholtz Zentrum München, Institute of Epidemiology I, Munich, Germany
- Lambertus A. Kiemeney
- Department for Health Evidence & Department of Urology, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands
- Philip Lazarus
- Department of Pharmaceutical Sciences, Washington State University College of Pharmacy, Spokane, WA, USA
- Loic Le Marchand
- University of Hawaii Cancer Center, Honolulu, HI, USA
- Geoffrey Liu
- Princess Margaret Hospital, Toronto, CA, USA
- Jose Mayordomo
- Division of Medical Oncology, University of Colorado, Aurora, CO
- Angela Risch
- Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL), Heidelberg, Germany
- Ann G. Schwartz
- Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA
- M. Dawn Teare
- School of Health and Related Research, University of Sheffield, Sheffield, UK
- Xifeng Wu
- Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- John K. Wiencke
- Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA
- Ping Yang
- Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA
- Zuo-Feng Zhang
- Department of Epidemiology, UCLA Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA, USA
- Margaret R. Spitz
- Baylor College of Medicine, Houston, TX, USA
- Christopher I. Amos
- Department of Community and Family Medicine, Geisel School of Medicine at Dartmouth, Hanover, NH, USA
- Laura J. Bierut
- Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA
- DOI
- https://doi.org/10.1016/j.ebiom.2016.08.012
- Journal volume & issue
-
Vol. 11,
no. C
pp. 219 – 226
Abstract
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.
Keywords
