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Meta-Analysis
. 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

Li-Shiun Chen  1 , Timothy Baker  2 , Rayjean J Hung  3 , Amy Horton  4 , Robert Culverhouse  5 , Sarah Hartz  4 , Nancy Saccone  6 , Iona Cheng  7 , Bo Deng  8 , Younghun Han  9 , Helen M Hansen  10 , Janet Horsman  11 , Claire Kim  12 , Albert Rosenberger  13 , Katja K Aben  14 , Angeline S Andrew  15 , Shen-Chih Chang  12 , Kai-Uwe Saum  16 , Hendrik Dienemann  17 , Dorothy K Hatsukami  18 , Eric O Johnson  19 , Mala Pande  20 , Margaret R Wrensch  10 , John McLaughlin  21 , Vidar Skaug  22 , Erik H van der Heijden  23 , Jason Wampfler  8 , Angela Wenzlaff  24 , Penella Woll  11 , Shanbeh Zienolddiny  22 , Heike Bickeböller  13 , Hermann Brenner  25 , Eric J Duell  26 , Aage Haugen  22 , Irene Brüske  27 , Lambertus A Kiemeney  28 , Philip Lazarus  29 , Loic Le Marchand  30 , Geoffrey Liu  31 , Jose Mayordomo  32 , Angela Risch  33 , Ann G Schwartz  24 , M Dawn Teare  34 , Xifeng Wu  20 , John K Wiencke  10 , Ping Yang  8 , Zuo-Feng Zhang  12 , Margaret R Spitz  35 , Christopher I Amos  9 , Laura J Bierut  36
Affiliations
Meta-Analysis

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 et al. EBioMedicine. 2016 Sep.

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.

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Figures

Fig. 1
Fig. 1
CHRNA5 rs16969968 predicts risk of lung cancer. Smoking cessation decreases probability of lung cancer regardless of CHRNA5 rs16969968 genotype. Quit: individuals who report having quit smoking when ascertained as cases of lung cancer or controls. N = 12,690 (6988 cases of lung cancer and 5702 controls). All participants have smoked at least 100 cigarettes (5833 active smokers, 6857 smokers who have quit). Adjusted for age, sex and rs16969968 genotype.
Fig. 2
Fig. 2
CHRNA5 rs16969968 predicts earlier lung cancer. Smoking cessation delays lung cancer, regardless of CHRNA5 rs16969968 genotype. Quit: individuals who report having quit smoking when ascertained as cases of lung cancer. N = 6,988 cases of lung cancer who are ever smokers. (3,471 current smokers, 3,517 former Smokers. Adjusted for sex, study, and rs16969968 genotype.
Fig. 3
Fig. 3
Summary diagram of CHRNA5 rs16969968 genotypes, smoking cessation, and lung cancer risks. *These associations are based on existing evidence (Chen et al., 2015a, Chen et al., 2015b).
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