Dataset Information

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: 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.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.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.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.

SUBMITTER: Chen LS

PROVIDER: S-EPMC5049934 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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

Chen Li-Shiun LS Baker Timothy T Hung Rayjean J RJ Horton Amy A Culverhouse Robert R Hartz Sarah S Saccone Nancy N Cheng Iona I Deng Bo B Han Younghun Y Hansen Helen M HM Horsman Janet J Kim Claire C Rosenberger Albert A Aben Katja K KK Andrew Angeline S AS Chang Shen-Chih SC Saum Kai-Uwe KU Dienemann Hendrik H Hatsukami Dorothy K DK Johnson Eric O EO Pande Mala M Wrensch Margaret R MR McLaughlin John J Skaug Vidar V van der Heijden Erik H EH Wampfler Jason J Wenzlaff Angela A Woll Penella P Zienolddiny Shanbeh S Bickeböller Heike H Brenner Hermann H Duell Eric J EJ Haugen Aage A Brüske Irene I Kiemeney Lambertus A LA Lazarus Philip P Le Marchand Loic L Liu Geoffrey G Mayordomo Jose J Risch Angela A Schwartz Ann G AG Teare M Dawn MD Wu Xifeng X Wiencke John K JK Yang Ping P Zhang Zuo-Feng ZF Spitz Margaret R MR Amos Christopher I CI Bierut Laura J LJ

EBioMedicine 20160810

<h4>Background</h4>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.<h4>Methods</h4>Meta-analyses exam ...[more]

PMID: 27543155

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Project description:BACKGROUND:Smoking is highly prevalent in Pakistan claiming the lives of over 100,000 individuals every year. A significant proportion of smokers (24.7%) make an attempt to quit each year but 97.4% fail to quit successfully. Little is known about the reasons for, and experiences of, failed quit attempts. This study was carried out to explore the experiences of young male smokers in quitting smoking in the twin cities of Pakistan METHOD: A qualitative study was carried out using a phenomenological approach in Rawalpindi and Islamabad. A total of 11 participants were interviewed. All study participants were male and had made at least one quit attempt. Study participants were a mix of smokers who failed to quit smoking, intermittent smokers and successful quitters. Streubert's (1991) method of phenomenology was followed during data analysis. RESULTS:The experiences of smokers while smoking "the smoking phase" have major effects on their journey towards quitting smoking. The smoking phase consists of three major stages: contact with initial smoking stimuli, the journey from first puff to enjoying smoking and then finally smoking becoming part of life. However, the journey towards quitting smoking is not as simple as the journey towards becoming a smoker. Instead, smokers get trapped in three overlapping cycles of smoking and quit attempts: smoking & forced quitting, smoking & intentional quitting, and smoking & intermittent smoking before successful quitting. Breaking the cycle is not easy in the presence of trapping factors (addiction, high availability, easy affordability, conducive social setup and low perceived risks of smoking). Three factors play a major role in breaking these cycles which are strong will power, continuous peer support and avoidance of smokers' company. CONCLUSION:A young smoker, during his experience of quitting smoking gets entrapped in several overlapping cycles of smoking & quit attempts before successful quitting. There are known entrapping factors as well as factors which help in breaking these cycles. Targeted interventions are needed to facilitate smoking cessation among young smokers in Pakistan.

Project description:CHRNA5-A3-B4 variants, rs16969968, rs588765 and rs578776, are consistently associated with tobacco consumption among smokers, but the association with smoking cessation is less consistent. Among the studies that reported significant associations with cessation, the effects were observed in smokers treated with placebo treatment in some studies and conversely in those receiving active pharmacological therapy (bupropion and nicotine replacement therapies) in others. Thus, it remains unclear whether CHRNA5-A3-B4 is a useful marker for optimizing smoking cessation. Using data from 654 Caucasian smokers treated with placebo, nicotine patch or varenicline, we investigated whether CHRNA5-A3-B4 variants were associated with smoking cessation outcomes, and whether there were significant genotype-by-treatment or haplotype-by-treatment interactions. We observed no significant associations between CHRNA5-A3-B4 variants and smoking cessation, despite replicating previous associations with baseline tobacco consumption. At end of treatment the effect size on smoking cessation in the placebo, patch and varenicline groups for rs16969968 [GG vs. GA+AA] was OR = 0.66 (P = 0.23), OR = 1.01 (P = 0.99), and OR = 1.30 (P = 0.36) respectively, of rs588765 [CC vs. CT+TT] was OR = 0.96 (P = 0.90), OR = 0.84 (P = 0.58), and OR = 0.74 (P = 0.29) respectively, and for rs578776 [GG vs. GA+AA] on smoking cessation was OR = 1.02 (P = 0.95), OR = 0.75 (P = 0.35), and OR = 1.20 (P = 0.51) respectively. Furthermore, we observed no associations with cessation using the CHRNA5-A3-B4 haplotype (constructed using rs16969968 and rs588765), nor did we observe any significant genotype-by-treatment interactions, with or without adjusting for the rate of nicotine metabolism (all P>0.05). We also observed no significant genetic associations with 6 month or 12 month smoking abstinence. In conclusion, we found no association between CHRNA5-A3-B4 variants and smoking cessation rates in this clinical trial; however, as expected, significant associations with baseline tobacco consumption were replicated. Our data suggest that CHRNA5-A3-B4 gene variants do not exhibit a robust association with smoking cessation and are unlikely to be useful for clinically optimizing smoking cessation pharmacotherapy for Caucasian smokers.

Dataset Information

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

Publications

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

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