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Impact of Neuro-Psychological Factors on Smoking-Associated Lung Cancer

Experimental Oncology Laboratory, Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, 2407 River Drive, Knoxville, TN 37996, USA
Cancers 2014, 6(1), 580-594;
Received: 25 December 2013 / Revised: 14 February 2014 / Accepted: 21 February 2014 / Published: 13 March 2014
(This article belongs to the Special Issue Tobacco-related Cancers)
PDF [441 KB, uploaded 13 March 2014]


Smoking has been extensively documented as a risk factor for all histological types of lung cancer and tobacco-specific nitrosamines and polycyclic aromatic hydrocarbons reproducibly cause lung cancer in laboratory rodents. However, the most common lung cancer, non-small cell lung cancer (NSCLC), frequently develops in never smokers and is particularly common in women and African Americans, suggesting that factors unrelated to smoking significantly impact this cancer. Recent experimental investigations in vitro and in animal models have shown that chronic psychological stress and the associated hyperactive signaling of stress neurotransmitters via β-adrenergic receptors significantly promote the growth and metastatic potential of NSCLC. These responses were caused by modulation in the expression and sensitization state of nicotinic acetylcholine receptors (nAChRs) that regulate the production of stress neurotransmitters and the inhibitory neurotransmitter γ-aminobutyric acid (GABA). Similar changes in nAChR-mediated neurotransmitter production were identified as the cause of NSCLC stimulation in vitro and in xenograft models by chronic nicotine. Collectively, these data suggest that hyperactivity of the sympathetic branch of the autonomic nervous system caused by chronic psychological stress or chronic exposure to nicotinic agonists in cigarette smoke significantly contribute to the development and progression of NSCLC. A recent clinical study that reported improved survival outcomes with the incidental use of β-blockers among patients with NSCLC supports this interpretation. View Full-Text
Keywords: smoking; non-small cell lung cancer; nicotinic receptors; b-adrenergic receptors; sympathicus hyperactivity; psychological stress smoking; non-small cell lung cancer; nicotinic receptors; b-adrenergic receptors; sympathicus hyperactivity; psychological stress

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Schuller, H.M. Impact of Neuro-Psychological Factors on Smoking-Associated Lung Cancer. Cancers 2014, 6, 580-594.

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