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

Abstract

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.

Neighborhood Deprivation and Lung Cancer Incidence and Mortality: A Multilevel Analysis from Sweden

“…No previous neighborhood study has, however, studied both incident and mortality cases of lung cancer. 34 A clinical study has also reported improved survival outcomes with the incidental use of β-blockers among patients with non-small-lung cancer, 35 which suppresses the sympathetic branch of the autonomic nervous system. This study was also unable to do so, although we adjusted for COPD, tobacco abuse, and alcoholism, in an attempt to adjust for potential surrogates for smoking.…”

Comprehensive review of epidemiological and animal studies on the potential carcinogenic effects of nicotineper se

“… 2012 ; Schuller 2012 ; Chu et al. 2013 ; Warren & Singh 2013 ; Grando 2014 ; Niu & Lu 2014 ; Schaal & Chellappan 2014 ; Schuller 2014 ). For example, nicotine has been reported to stimulate cell proliferation, inhibit apoptosis, induce cell migration and invasion, induce angiogenesis and inhibit immune functions.…”

Chronic Stress Facilitates Lung Tumorigenesis by Promoting Exocytosis of IGF2 in Lung Epithelial Cells

“…However, chronic stress was found to promote tumor growth in immunodeficient nude mice carrying defects in immune functions (6,9,(33)(34)(35). Hence, additional mechanisms, such as somatic mutations, genomic instability, and inhibited apoptosis, have been proposed to explain the effects of chronic stress on tumor development (5,35). Our study provides direct evidence that the norepinephrineinduced activation of IGF-1R in lung epithelial cells is a biochemical event that promotes lung carcinogenesis.…”

“…Chronic stress has been implicated in the onset and progression of various cancers, including lung cancer (6,9,13,(33)(34)(35). Lung cancer patients with severe psychologic distress at the time of diagnosis had frequently experienced earlier psychologic stress (36), and psychologic distress was found to be a significant predictor of lung cancer mortality (37).…”

“…These impairments can include altered cytokine production, cytotoxicity in natural killer (NK) cells, and T-cell mitogenesis (38). However, chronic stress was found to promote tumor growth in immunodeficient nude mice carrying defects in immune functions (6,9,(33)(34)(35). Hence, additional mechanisms, such as somatic mutations, genomic instability, and inhibited apoptosis, have been proposed to explain the effects of chronic stress on tumor development (5,35).…”