title: Genetic Risk Can Be Decreased: Quitting Smoking Decreases and Delays Lung Cancer for Smokers With High and Low CHRNA5 Risk Genotypes - A Meta-Analysis.
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.
  
  
  CONCLUSIONS
  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 7years 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.
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA; Siteman Cancer Center, Washington University, St. Louis, MO, USA. Electronic address: chenli@psychiatry.wustl.edu.
authors.forename: Li-Shiun
authors.initials: LS
authors.lastname: Chen
authors.affiliation: Tobacco Research and Intervention, University of Wisconsin, School of Medicine, Madison, WI, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: Baker
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada.
authors.forename: Rayjean J
authors.initials: RJ
authors.lastname: Hung
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Horton
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, MO.
authors.forename: Robert
authors.initials: R
authors.lastname: Culverhouse
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Hartz
authors.affiliation: Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Nancy
authors.initials: N
authors.lastname: Saccone
authors.affiliation: Cancer Prevention Institute of California, Fremont, CA, USA.
authors.forename: Iona
authors.initials: I
authors.lastname: Cheng
authors.affiliation: Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Deng
authors.affiliation: Department of Community and Family Medicine, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
authors.forename: Younghun
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Helen M
authors.initials: HM
authors.lastname: Hansen
authors.affiliation: Department of Oncology, University of Sheffield, Sheffield, UK.
authors.forename: Janet
authors.initials: J
authors.lastname: Horsman
authors.affiliation: Department of Epidemiology, UCLA Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Claire
authors.initials: C
authors.lastname: Kim
authors.affiliation: Department of Genetic Epidemiology, University of Goettingen Medical School, Goettingen, Germany.
authors.forename: Albert
authors.initials: A
authors.lastname: Rosenberger
authors.affiliation: Netherlands Comprehensive Cancer Organization, Utrecht, The Netherlands & Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands.
authors.forename: Katja K
authors.initials: KK
authors.lastname: Aben
authors.affiliation: Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
authors.forename: Angeline S
authors.initials: AS
authors.lastname: Andrew
authors.affiliation: Department of Epidemiology, UCLA Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Shen-Chih
authors.initials: SC
authors.lastname: Chang
authors.affiliation: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Kai-Uwe
authors.initials: KU
authors.lastname: Saum
authors.affiliation: Department of Thoracic Surgery, Thoraxklinik at University Hospital Heidelberg, Heidelberg, Germany; Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL), Heidelberg, Germany.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Dienemann
authors.affiliation: Department of Psychiatry, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Dorothy K
authors.initials: DK
authors.lastname: Hatsukami
authors.affiliation: Division of Health, Social and Economic Research, Research Triangle Institute, International, Research Triangle Park, NC 27709, USA.
authors.forename: Eric O
authors.initials: EO
authors.lastname: Johnson
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Mala
authors.initials: M
authors.lastname: Pande
authors.affiliation: Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Wrensch
authors.affiliation: Public Health Ontario, Toronto, Canada.
authors.forename: John
authors.initials: J
authors.lastname: McLaughlin
authors.affiliation: Department of Biological and Chemical Work Environment, National Institute of Occupational Health, Oslo, Norway.
authors.forename: Vidar
authors.initials: V
authors.lastname: Skaug
authors.affiliation: Department for Lung Diseases, Radboud University Medical Centre, Radboud Institute for Health Sciences, Nijmegen, The Netherlands.
authors.forename: Erik H
authors.initials: EH
authors.lastname: van der Heijden
authors.affiliation: Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Wampfler
authors.affiliation: Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Wenzlaff
authors.affiliation: Department of Oncology, University of Sheffield, Sheffield, UK.
authors.forename: Penella
authors.initials: P
authors.lastname: Woll
authors.affiliation: Department of Biological and Chemical Work Environment, National Institute of Occupational Health, Oslo, Norway.
authors.forename: Shanbeh
authors.initials: S
authors.lastname: Zienolddiny
authors.affiliation: Department of Genetic Epidemiology, University of Goettingen Medical School, Goettingen, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Bickeböller
authors.affiliation: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany; Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Brenner
authors.affiliation: Unit of Nutrition, Environment and Cancer, Epidemiology Program, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Duell
authors.affiliation: Department of Biological and Chemical Work Environment, National Institute of Occupational Health, Oslo, Norway.
authors.forename: Aage
authors.initials: A
authors.lastname: Haugen
authors.affiliation: Helmholtz Zentrum München, Institute of Epidemiology I, Munich, Germany.
authors.forename: Irene
authors.initials: I
authors.lastname: Brüske
authors.affiliation: Department for Health Evidence & Department of Urology, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands.
authors.forename: Lambertus A
authors.initials: LA
authors.lastname: Kiemeney
authors.affiliation: Department of Pharmaceutical Sciences, Washington State University College of Pharmacy, Spokane, WA, USA.
authors.forename: Philip
authors.initials: P
authors.lastname: Lazarus
authors.affiliation: University of Hawaii Cancer Center, Honolulu, HI, USA.
authors.forename: Loic
authors.initials: L
authors.lastname: Le Marchand
authors.affiliation: Princess Margaret Hospital, Toronto, CA, USA.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Liu
authors.affiliation: Division of Medical Oncology, University of Colorado, Aurora, CO.
authors.forename: Jose
authors.initials: J
authors.lastname: Mayordomo
authors.affiliation: Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL), Heidelberg, Germany; Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Heidelberg, Germany; Div. Molecular Biology, University of Salzburg, Austria; Cancer Cluster Salzburg, Austria.
authors.forename: Angela
authors.initials: A
authors.lastname: Risch
authors.affiliation: Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA.
authors.forename: Ann G
authors.initials: AG
authors.lastname: Schwartz
authors.affiliation: School of Health and Related Research, University of Sheffield, Sheffield, UK.
authors.forename: M Dawn
authors.initials: MD
authors.lastname: Teare
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Xifeng
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
authors.forename: John K
authors.initials: JK
authors.lastname: Wiencke
authors.affiliation: Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.affiliation: Department of Epidemiology, UCLA Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Zuo-Feng
authors.initials: ZF
authors.lastname: Zhang
authors.affiliation: Baylor College of Medicine, Houston, TX, USA.
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Spitz
authors.affiliation: Department of Community and Family Medicine, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Amos
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA; Siteman Cancer Center, Washington University, St. Louis, MO, USA.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Bierut
mesh_terms: D017668:Age of Onset; D000483:Alleles; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000453:epidemiology* / Q000209:etiology*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016017:Odds Ratio; D011379:Prognosis; D011978:Receptors, Nicotinic / Q000235:genetics*; D012306:Risk; D012907:Smoking; D016540:Smoking Cessation
chemical_list: C447158:CHRNA5 protein, human; D009419:Nerve Tissue Proteins; D011978:Receptors, Nicotinic
keywords: Genetics; Lung cancer; Meta-analysis; Smoking cessation