Elsevier

Clinical Lung Cancer

Volume 21, Issue 2, March 2020, Pages 171-176
Clinical Lung Cancer

Original Study
Association Between Nicotine-dependent Gene Polymorphism and Smoking Cessation in Patients With Lung Cancer

https://doi.org/10.1016/j.cllc.2019.07.002Get rights and content

Abstract

Background

Patients with lung cancer continue to smoke owing to complex factors. Failure to quit smoking (defined as nicotine dependence) is significantly associated with genetic status. This study aimed to investigate the relationship between polymorphisms in nicotine dependence genes and smoking status after the diagnosis of lung cancer.

Patients and Methods

A total of 240 patients with lung cancer were included from July 2017 to March 2018. According to the actual smoking condition after lung cancer diagnosis, eligible patients were divided into 3 groups: the never-smoking group, the failure to quit smoking group, and the successful smoking cessation group. Fagerstrom Test for Nicotine Dependence scores were used to evaluate the smoking status of each group. Three nicotine-dependent genes with 6 loci were detected.

Results

Among the 240 patients, 86 were never-smokers, 51 failed to quit smoking, and 104 successfully quit smoking. The initial age of smoking in the failure to quit smoking group was significantly younger than those in the successful smoking cessation group (P = .001). There was a significant difference in the GG and AG and AA genotype distributions of CHRNA3 (rs578776) among the 3 groups (P = .003). There was also a significant difference in the distribution of CHRNA4 (rs2229959) genotypes among the 3 groups (P = .003). However, there was no significant difference in the genotype distribution of CHRNA5 (rs588765) among the 3 groups (P = .277).

Conclusions

Gene polymorphisms of CHRNA3 (rs578776) and CHRNA4 (rs1044396 and rs2229959) were associated with the success of smoking cessation after the diagnosis of lung cancer, which should be considered in the management of smoking cessation after patients are diagnosed with lung cancer.

Introduction

Smoking is one of the independent risk factors of lung cancer. Smoking cessation is of great clinical significance for the prevention and treatment of lung cancer. Previous studies have reported that a high proportion (range, 26.6%-50.0%) of patients with smoking history would continue to smoke after a diagnosis of lung cancer,1, 2 suggesting that smoking continuation after the diagnosis of lung cancer remains a critical issue in the management of patients with lung cancer.

According to the 2014 United States Department of Health report, smoking could significantly increase the overall and specific mortality rates among patients with cancer and survivors, as well as the risk of secondary primary tumors.3 Smoking continuation after initial diagnosis has various epidemiologic and genetic factors. If we could find the specific factors that influence the failure of smoking cessation, we could conduct targeted intervention, and then the objective of accurate smoking cessation can be achieved. Our previous results showed that pain, quit attempts, and sleep quality were significantly correlated with the Fagerstrom Test for Nicotine Dependence (FTND) scores. However, all of the factors could explain part of the reasons for failure of smoking cessation. One-third of smokers failed to quit smoking without clear explanations.

Failure to quit smoking (defined as nicotine dependence) is significantly related to genetic status. Several studies reported that single nucleotide polymorphisms (SNPs) of the nicotinic acetylcholine receptor alpha 4 subunits (CHRNA4) were significantly associated with nicotine dependence.4, 5, 6, 7, 8 For example, a retrospective study including 348 patients with smoking nicotine tolerance score ≥ 4 showed that CHRNA4 (rs2229959 and rs1044396), CHRNB2, brain-derived neurotrophic factor, and neurotrophic tyrosine kinase receptor 2 were independently associated with nicotine dependence.9 Lior et al showed that CHRNA5 (rs588765 and rs16969968) and CHRNA3 (rs578776) were significantly associated with patients’ nicotine dependence and the onset time of Parkinson’s disease.10 Chen et al’s study also reported that the CHRNA5-A3-B4 nicotine receptor gene was associated with nicotine dependence and psychological disorders.11 Although these studies examined the different types of nicotine dependence on related genes, they did not further divide the patients into different groups according to the actual smoking condition after cancer diagnosis. Moreover, they did not explore the impact of SNPs of these genes on the nicotine dependence of patients with lung cancer.

Considering the significant role of smoking in the development and progression of lung cancer, it is necessary to investigate the relationship between the abovementioned gene SNPs and nicotine dependence in patients with lung cancer and their role in the failure to quit smoking after a diagnosis of lung cancer. The current study will provide the basis of the genetic classification for building a health management model of quitting smoking for patients with lung cancer.

Section snippets

Patient Cohort

Patients with histologically or pathologically diagnosed lung cancer from Shanghai Pulmonary Hospital were included in this study from July 2017 to March 2018. According to the actual smoking condition, patients were divided into the never-smoking group, the failure of smoking cessation group, and the success of smoking cessation group. Smokers are defined as those who answer that they are still smoking or that they are not smoking at present, but urinary cotinine level is equal to or higher

Baseline Features of Patients in Each Group

In total, 240 patients were included. Among them, 234 (97.5%) were males, 235 (97.9%) were patients with non–small-cell lung cancer (NSCLC), and 6 (2.1%) were patients with small-cell lung cancer. The patients’ ages ranged from 36 to 80 years old, and their mean age was 61 years old. The median nicotine tolerance score in the failure of the smoking cessation group was 2. Eighty-six were never smokers, 51 failed to quit smoking, and 104 successfully quit smoking. There was no significant

Discussion

In this study, we found that patients with lung cancer in the failure to quit smoking group had a significantly higher smoking duration and younger initial smoking age than those in the successful smoking cessation group. Moreover, we first reported that patients with the GG genotype in CHRNA3 (rs578776), the AA genotype in CHRNA4 (rs1044396), and the CC genotype in CHRNA4 (rs2229959) were more likely to quit smoking successfully.

The Coronary Artery Risk Development in Young Adults (CARDIA)

Conclusions

This is the first study to investigate the relationship between nicotine dependence and genotypes according to smoking status in Chinese patients with lung cancer. Health care workers should pay attention to the duration of smoking and the initial age of smoking of patients who failed to quit smoking after a diagnosis of lung cancer. SNPs of CHRNA3 (rs578776) and CHRNA4 (rs1044396 and rs2229959) were associated with the success of smoking cessation after the diagnosis of lung cancer.

Disclosure

The authors have stated that they have no conflicts of interest.

Acknowledgments

This study was supported by the Eagle Plan of Shanghai Pulmonary Hospital (No. HR2016001) and the Program of National Natural Science Foundation of China (71904144).

References (32)

F.G. and Ch.Z. contributed equally to this article as first authors.

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