Nicotinic Acetylcholine Receptor Polymorphism, Smoking Behavior, and Tobacco-Related Cancer and Lung and Cardiovascular Diseases: A Cohort Study

Kaur-Knudsen, Diljit; Bojesen, Stig E.; Tybjærg‐Hansen, Anne; Nordestgaard, Børge G.

doi:10.1200/jco.2010.32.9870

Cited by 50 publications

(53 citation statements)

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“…We also confirmed the associations between this variance and incident COPD 4, 13, 14, tobacco‐related cancers 7, 15, 16, lung cancer 4, 7, 15, 17, 18, 19, 20, 21 and smoking quantity 2, 3, 7, indicating an exciting overlap of genetic influence on ND and smoking‐related diseases. As mentioned above, this region of the nAChRs is characterized by high correlation and the results should be interpreted as an association with the cluster instead of the rs1051730.…”

Section: Discussionsupporting

confidence: 75%

Gene variance in the nicotinic receptor cluster (CHRNA5‐CHRNA3‐CHRNB4) predicts death from cardiopulmonary disease and cancer in smokers

et al. 2015

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BackgroundGenetic variation in the cluster on chromosome 15, encoding the nicotinic acetylcholine receptor subunits (CHRNA5‐CHRNA3‐CHRNB4), has shown strong associations with tobacco consumption and an additional risk increase in smoking‐related diseases such as chronic obstructive pulmonary disease (COPD), peripheral artery disease and lung cancer.ObjectivesTo test whether rs1051730 (C/T), a tag for multiple variants in the CHRNA5‐CHRNA3‐CHRNB3 cluster, is associated with a change in risk of smoking‐related mortality and morbidity in the Malmö Diet and Cancer study, a population‐based prospective cohort study.MethodsAt baseline participants were classified as current (n = 6951), previous (n = 8426) or never (n = 9417) smokers. Cox‐proportional hazards models were used to determine the correlation between rs1051730 and incidence of first COPD, tobacco‐related cancer, other cancer and cardiovascular disease (CVD), and total mortality due to these causes, during approximately 14 years of follow‐up.ResultsAmongst current smokers there were 480 first incident COPD events, 852 tobacco‐related cancers, 810 other cancers and 1022 CVD events. A total of 1508 deaths occurred, including 500 due to CVD, 102 due to respiratory diseases and 677 due to cancer. In adjusted additive models, an increasing number of T alleles were associated with a gradual increase in total mortality, incident COPD and tobacco‐related cancer, even after adjustment for smoking quantity. No significant associations were observed amongst never smokers.ConclusionOur data suggest that gene variance in the CHRNA5‐CHRNA3‐CHRNB4 cluster is associated with an increased risk of death, incidence of COPD and tobacco‐related cancer in smokers. These findings indicate an individual susceptibility to tobacco use and its complications; this may be important when targeting and designing smoking cessation therapies.

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Section: Discussionsupporting

confidence: 75%

Gene variance in the nicotinic receptor cluster (CHRNA5‐CHRNA3‐CHRNB4) predicts death from cardiopulmonary disease and cancer in smokers

et al. 2015

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“…Several recent studies have focused on the role of genetic variants in association with smoking behavior. In more than 10,000 participants from the general population of Denmark, Kaur-Knudsen and colleagues (38) examined the association between nicotinic acetylcholine receptor genotype and smoking behavior and the added effect of this association on the risk of tobacco-related diseases such as lung and bladder cancer, COPD, and cardiovascular diseases. They reported an association between the nicotinic acetylcholine receptor genotype and daily tobacco consumption, cumulative tobacco consumption, and smoking inhalation but not with age of smoking onset, age of smoking cessation, or smoking duration.…”

Section: Copd Biologymentioning

confidence: 99%

Genetic Predisposition to Chronic Obstructive Pulmonary Disease and/or Lung Cancer: Important Considerations When Evaluating Risk

El‐Zein

Young

Hopkins

et al. 2012

Cancer Prevention Research

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Chronic obstructive pulmonary disease (COPD) is defined as a disease causing an airflow limitation that is not fully reversible. COPD is phenotypically complex and characterized by small-airway disease and/or emphysema that result from the interaction between host genetic susceptibility and environmental exposures. As in lung cancer, smoking exposure is the most important risk factor for the development of COPD, accounting for 80% to 90% of all cases. COPD affects an estimated 8% to 10% of the general adult population, 15% to 20% of the smoking population, and 50% to 80% of lung cancer patients (with substantial smoking histories). In prospective studies, COPD has been found to be an independent risk factor for lung cancer, conferring a three-to 10-fold increased risk of lung cancer when compared with smokers without COPD. These findings suggest that smokers have a host susceptibility to COPD alone, COPD and lung cancer (i.e., overlap), and lung cancer in the absence of COPD. This minireview focuses on important points that need to be addressed when studying genetic susceptibility factors for COPD and its complex relationship with susceptibility to lung cancer. Cancer Prev Res; 5(4); 522-7. Ó2012 AACR.

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“…This genotype was also associated with lung cancer and nicotine dependence in several other studies [2][3][4][5]. So far, the scientific evidence on COPD and lung function for the CHRNA3 polymorphism mostly stems from case-control studies with high smoking exposure.…”

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confidence: 91%

“…However, we present results from a large general-population sample. Although, in the Copenhagen City Heart Study, we previously found that the CHRNA3 rs1051730 genotype was associated with COPD hospitalisation [5] and a recent meta-analysis implicated several other polymorphisms in other genes in affecting lung function [6], the influence of this genotype on slight changes in lung function in smokers in the general population is largely unknown. Likewise, the association of this genotype with COPD of different severities and defined using different spirometric criteria is unexplored in the general population.…”

mentioning

confidence: 96%

“…Secondly, we tested whether the genotype was associated with COPD defined using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria of increasing severity (GOLD stages I-IV, II-IV and III-IV) [9], defined by the lower limit of normal for the forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio [10] and defined as hospitalisation with COPD [11,12]. To answer these questions with maximum power, we studied 57,657 individuals from the Danish general population, the Copenhagen General Population Study cohort, of whom 54,289 had spirometry performed and 34,592 were ever-smokers; this is a different sample of the Danish general population from that in our previous study [5]. In addition, the large size of our study allowed us to investigate associations with COPD severity stages.…”

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confidence: 99%

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CHRNA3genotype, nicotine dependence, lung function and disease in the general population

2012

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The CHRNA3 rs1051730 polymorphism has been associated to chronic obstructive pulmonary disease (COPD), lung cancer and nicotine dependence in case-control studies with high smoking exposure; however, its influence on lung function and COPD severity in the general population is largely unknown.We genotyped 57,657 adult individuals from the Copenhagen General Population Study, of whom 34,592 were ever-smokers. Information on spirometry, hospital admissions, smoking behaviour and use of nicotinic replacement therapy was recorded.In homozygous (11%), heterozygous (44%) and noncarrier (45%) ever-smokers, forced expiratory volume in 1 s (FEV1) was 94.1% predicted, 95.3% pred and 96.5% pred, forced vital capacity (FVC) was 97.1% pred, 97.5% pred and 98.3% pred, and FEV1/FVC was 0.770, 0.773 and 0.777, respectively (all p,0.001 for trend). Smoking interacted with genotype on FEV1 % pred and FEV1/FVC (both p,0.001). When adjusted for cumulative tobacco consumption, these associations remained significant. In ever-smokers, odds ratios for COPD in homozygotes versus noncarriers were 1.3 (95% CI 1.2-1.4) for Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages I-IV, 1.4 (95% CI 1.2-1.6) for GOLD II-IV and 1.7 (95% CI 1.3-2.1) for GOLD III-IV. The corresponding value for lung cancer was 1.8 (95% CI 1.2-2.6). Genotype was also associated with daily and cumulative tobacco consumption and with use of nicotinic replacement therapy in former smokers.In ever-smokers, the CHRNA3 rs1051730 genotype associated with reduced lung function and increased COPD severity.

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Nicotinic Acetylcholine Receptor Polymorphism, Smoking Behavior, and Tobacco-Related Cancer and Lung and Cardiovascular Diseases: A Cohort Study

Cited by 50 publications

References 25 publications

Gene variance in the nicotinic receptor cluster (CHRNA5‐CHRNA3‐CHRNB4) predicts death from cardiopulmonary disease and cancer in smokers

Gene variance in the nicotinic receptor cluster (CHRNA5‐CHRNA3‐CHRNB4) predicts death from cardiopulmonary disease and cancer in smokers

Genetic Predisposition to Chronic Obstructive Pulmonary Disease and/or Lung Cancer: Important Considerations When Evaluating Risk

CHRNA3genotype, nicotine dependence, lung function and disease in the general population

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