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EBioMedicine. 2016 Sep;11:219-226. doi: 10.1016/j.ebiom.2016.08.012. Epub 2016 Aug 10.

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

Author information

1
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.
2
Tobacco Research and Intervention, University of Wisconsin, School of Medicine, Madison, WI, USA.
3
Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada.
4
Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
5
Department of Medicine, Washington University School of Medicine, St. Louis, MO.
6
Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA.
7
Cancer Prevention Institute of California, Fremont, CA, USA.
8
Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA.
9
Department of Community and Family Medicine, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
10
Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
11
Department of Oncology, University of Sheffield, Sheffield, UK.
12
Department of Epidemiology, UCLA Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA, USA.
13
Department of Genetic Epidemiology, University of Goettingen Medical School, Goettingen, Germany.
14
Netherlands Comprehensive Cancer Organization, Utrecht, The Netherlands & Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands.
15
Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
16
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
17
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.
18
Department of Psychiatry, University of Minnesota, Minneapolis, MN, USA.
19
Division of Health, Social and Economic Research, Research Triangle Institute, International, Research Triangle Park, NC 27709, USA.
20
Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
21
Public Health Ontario, Toronto, Canada.
22
Department of Biological and Chemical Work Environment, National Institute of Occupational Health, Oslo, Norway.
23
Department for Lung Diseases, Radboud University Medical Centre, Radboud Institute for Health Sciences, Nijmegen, The Netherlands.
24
Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA.
25
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.
26
Unit of Nutrition, Environment and Cancer, Epidemiology Program, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain.
27
Helmholtz Zentrum München, Institute of Epidemiology I, Munich, Germany.
28
Department for Health Evidence & Department of Urology, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands.
29
Department of Pharmaceutical Sciences, Washington State University College of Pharmacy, Spokane, WA, USA.
30
University of Hawaii Cancer Center, Honolulu, HI, USA.
31
Princess Margaret Hospital, Toronto, CA, USA.
32
Division of Medical Oncology, University of Colorado, Aurora, CO.
33
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.
34
School of Health and Related Research, University of Sheffield, Sheffield, UK.
35
Baylor College of Medicine, Houston, TX, USA.
36
Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA; Siteman Cancer Center, Washington University, St. Louis, MO, USA.

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 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.

KEYWORDS:

Genetics; Lung cancer; Meta-analysis; Smoking cessation

PMID:
27543155
PMCID:
PMC5049934
DOI:
10.1016/j.ebiom.2016.08.012
[Indexed for MEDLINE]
Free PMC Article

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