Generic placeholder image

Recent Patents on Anti-Cancer Drug Discovery


ISSN (Print): 1574-8928
ISSN (Online): 2212-3970

Review Article

Tobacco Smoking: Risk to Develop Addiction, Chronic Obstructive Pulmonary Disease, and Lung Cancer

Author(s): Alessia Santoro, Carlo Tomino, Giulia Prinzi, Palma Lamonaca, Vittorio Cardaci, Massimo Fini and Patrizia Russo*

Volume 14, Issue 1, 2019

Page: [39 - 52] Pages: 14

DOI: 10.2174/1574892814666190102122848


Background: The morbidity and mortality associated with tobacco smoking is well established. Nicotine is the addictive component of tobacco. Nicotine, through the non-neuronal α7nicotinic receptor, induces cell proliferation, neo-angiogenesis, epithelial to mesenchymal transition, and inhibits drug-induced apoptosis.

Objective: To understand the genetic, molecular and cellular biology of addiction, chronic obstructive pulmonary disease and lung cancer.

Methods: The search for papers to be included in the review was performed during the months of July- September 2018 in the following databases: PubMed (, Scopus (, EMBASE (, and ISI Web of Knowledge ( The following searching terms: “nicotine”, “nicotinic receptor”, and “addiction” or “COPD” or “lung cancer” were used.

Patents were retrieved in ( All papers written in English were evaluated. The reference list of retrieved articles was also reviewed to identify other eligible studies that were not indexed by the above-mentioned databases.

New experimental data on the ability of nicotine to promote transformation of human bronchial epithelial cells, exposed for one hour to Benzo[a]pyrene-7,8-diol-9-10-epoxide, are reported.

Results: Nicotinic receptors variants and nicotinic receptors upregulation are involved in addiction, chronic obstructive pulmonary disease and/or lung cancer. Nicotine through α7nicotinic receptor upregulation induces complete bronchial epithelial cells transformation.

Conclusion: Genetic studies highlight the involvement of nicotinic receptors variants in addiction, chronic obstructive pulmonary disease and/or lung cancer. A future important step will be to translate these genetic findings to clinical practice. Interventions able to help smoking cessation in nicotine dependence subjects, under patent, are reported.

Keywords: Addiction, cancer hallmarks, COPD, genetic variant, lung cancer, nicotine, nicotinic receptor, patent.

Gakidou E, Afshin A, Abajobir AA, Abate KH, Abbafati C, Abbas KM, et al. GBD 2016 Risk Factors Collaborators. Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet 2017; 390(10100): 1345-422.
Warren GW, Alberg AJ, Kraft AS, Cummings KM. The 2014 Surgeon General’s report: “The Health Consequences of Smoking-50 Years of Progress”: A paradigm shift in cancer care. Cancer 2014; 120(13): 1914-6.
Benowitz NL. Nicotine addiction. N Engl J Med 2010; 362(24): 2295-303.
Russo P, Nastrucci C, Alzetta G, Szalai C. Tobacco habit: Historical, cultural, neurobiological, and genetic features of people’s relationship with an addictive drug. Perspect Biol Med 2011; 54(4): 557-77.
Russo P, Cesario A, Rutella S, Veronesi G, Spaggiari L, Galetta D, et al. Impact of genetic variability in nicotinic acetylcholine receptors on nicotine addiction and smoking cessation treatment. Curr Med Chem 2011; 18(1): 91-112.
Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition Edited by American Psychiatric Association (accessed September 2018).
Koob GF, Volkow ND. Neurobiology of addiction: a neurocircuitry analysis. Lancet Psychiatry 2016; 3(8): 760-73.
Soloway SB. Naturally occurring insecticides. Environ Health Perspect 1976; 14: 109-17.
Eastham HM, Lind RJ, Eastlake JL, Clarke BS, Towner P, Reynolds SE, et al. Characterization of a nicotinic acetylcholine receptor from the insect Manduca sexta. Eur J Neurosci 1998; 10(3): 879-89.
Hudkins M, O'Neill J, Tobias MC, Bartzokis G, London ED. Cigarette smoking and white matter microstructure. Psychopharmacol 2010; 221: 285e295.
Liao Y, Tang J, Deng Q, Deng Y, Luo T, Wang X, et al. Bilateral fronto-parietal integrity in young chronic cigarette smokers: A diffusion tensor imaging study. PLoS One 2011; 6: e26460.
Yamada T, Fujii T, Kanai T, Amo T, Imanaka T, Nishimasu H, et al. Expression of acetylcholine (ACh) and ACh-synthesizing activity in Archaea. Life Sci 2005; 77(16): 1935-44.
Karczmar AG. Cholinesterases (ChEs) and the cholinergic system in ontogenesis and phylogenesis, and non-classical roles of cholinesterases - A review. Chem Biol Interact 2010; 187(1-3): 34-43.
Wessler I, Kirkpatrick CJ. Acetylcholine beyond neurons: the non-neuronal cholinergic system in humans. Br J Pharmacol 2008; 154(8): 1558-71.
Grando SA, Kawashima K, Kirkpatrick CJ, Meurs H, Wessler I. The non-neuronal cholinergic system: Basic science, therapeutic implications and new perspectives. Life Sci 2012; 91(21-22): 969-72.
Cardinale A, Nastrucci C, Cesario A, Russo P. Nicotine: Specific role in angiogenesis, proliferation and apoptosis. Crit Rev Toxicol 2012; 42(1): 68-89.
Wessler IK, Kirkpatrick CJ. Activation of muscarinic receptors by non-neuronal acetylcholine. Handb Exp Pharmacol 2012; 208: 469-91.
Changeux JP. The nicotinic acetylcholine receptor: the founding father of the pentameric ligand-gated ion channel superfamily. J Biol Chem 2012; 287: 40207-15.
Hurst R, Rollema H, Bertrand D. Nicotinic acetylcholine receptors: From basic science to therapeutics. Pharmacol Ther 2013; 137(1): 22-54.
Changeux JP, Corringer PJ, Maskos U. The nicotinic acetylcholine receptor: From molecular biology to cognition. Neuropharmacology 2015; (96): 135-6.
Campos MW, Serebrisky D, Castaldelli-Maia JM. Smoking and cognition. Curr Drug Abuse Rev 2016; 9(2): 76-9.
Picciotto MR, Mineur YS. Molecules and circuits involved in nicotine addiction: The many faces of smoking. Neuropharmacology 2014; 76(Pt B): 545-3.
Thorgeirsson TE, Gudbjartsson DF, Surakka I, Vink JM, Amin N, Geller F, et al. Sequence variants at CHRNB3-CHRNA6 and CYP2A6 affect smoking behavior. Nat Genet 2010; 42(5): 448-53.
Hung RJ, McKay JD, Gaborieau V, Boffetta P, Hashibe M, Zaridze D, et al. Susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25. Nature 2008; 452(187): 633-7.
Amos CI, Wu X, Broderick P, Gorlov IP, Gu J, Eisen T, et al. Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1. Nat Genet 2008; 40(5): 616-22.
Bierut LJ. Convergence of genetic findings for nicotine dependence and smoking related diseases with chromosome 15q24-25. Trends Pharmacol Sci 2010; 31(1): 46-51.
Kuryatov A, Onksen J, Lindstrom J. Roles of accessory subunits in alpha4-beta2(*) nicotinic receptors. Mol Pharmacol 2008; 74(1): 132-43.
Tammimäki A, Herder P, Li P, Esch C, Laughlin JR, Akk G, et al. Impact of human D398N single nucleotide polymorphism on intracellular calcium response mediated by α3β4α5 nicotinic acetylcholine receptors. Neuropharmacol 2012; 63(6): 1002-11.
Lassi G, Taylor AE, Timpson NJ, Kenny PJ, Mather RJ, Eisen T, et al. The CHRNA5-A3-B4 gene cluster and smoking: From discovery to therapeutics. Trends Neurosci 2016; 39(12): 851-61.
Sherva R, Wilhelmsen K, Pomerleau CS, Chasse SA, Rice JP, Snedecor SM, et al. Association of a single nucleotide polymorphism in neuronal acetylcholine receptor subunit alpha 5 (CHRNA5) with smoking status and with ‘pleasurable buzz’ during early experimentation with smoking. Addiction 2008; 103(9): 1544-52.
Le Marchand L, Derby KS, Murphy SE, Hecht SS, Hatsukami D, Carmella SG, et al. Smokers with the CHRNA lung cancer-associated variants are exposed to higher levels of nicotine equivalents and a carcinogenic tobacco-specific nitrosamine. Cancer Res 2008; 68(22): 9137-40.
Hong LE, Hodgkinson CA, Yang Y, Sampath H, Ross TJ, Buchholz B, et al. A genetically modulated, intrinsic cingulate circuit supports human nicotine addiction. Proc Natl Acad Sci USA 2010; 107(10): 13509-14.
Smith RM, Alachkar H, Papp AC, Wang D, Mash DC, Wang JC, et al. Nicotinic alpha5 receptor subunit mRNA expression is associated with distant 59 upstream polymorphisms. Eur J Hum Genet 2011; 19(1): 76-83.
Wang JC, Cruchaga C, Saccone NL, Bertelsen S, Liu P, Budde JP, et al. Risk for nicotine dependence and lung cancer is conferred by mRNA expression levels and amino acid change in CHRNA5. Hum Mol Genet 2009; 18(16): 3125-35.
Wang Y, Lee JW, Oh G, Grady SR, McIntosh JM, Brunzell DH, et al. Enhanced synthesis and release of dopamine in transgenic mice with gain-of-function α6* nAChRs. J Neurochem 2014; 129(2): 315-27.
Gotti C, Zoli M, Clementi F. Brain nicotinic acetylcholine receptors: Native subtypes and their relevance. Trends Pharmacol Sci 2006; 27(9): 482-91.
Lindstrom JM. Nicotinic acetylcholine receptors of muscles and nerves: Comparison of their structures, functional roles, and vulnerability to pathology. Ann N Y Acad Sci 2003; 998: 41-52.
Saccone SF, Hinrichs AL, Saccone NL, Chase GA, Konvicka K, Madden PA, et al. Cholinergic nicotinic receptor genes implicated in a nicotine dependence association study targeting 348 candidate genes with 3713 SNPs. Hum Mol Genet 2007; 16(1): 36-49.
Saccone NL, Wang JC, Breslau N, Johnson EO, Hatsukami D, Saccone SF, et al. The CHRNA5-CHRNA3-CHRNB4 nicotinic receptor subunit gene cluster affects risk for nicotine dependence in African-Americans and in European-Americans. Cancer Res 2009; 69(17): 6848-56.
Tournier JM, Maouche K, Coraux C, Zahm JM, Cloëz-Tayarani I, Nawrocki-Raby B, et al. alpha3alpha5beta2-Nicotinic acetylcholine receptor contributes to the wound repair of the respiratory epithelium by modulating intracellular calcium in migrating cells. Am J Pathol 2006; 168(1): 55-68.
Krais AM, Hautefeuille AH, Cros MP, Krutovskikh V, Tournier JM, Birembaut P, et al. CHRNA5 as negative regulator of nicotine signaling in normal and cancer bronchial cells: Effects on motility, migration and p63 expression. Carcinogenesis 2011; 32(9): 1388-95.
Halldén S, Sjögren M, Hedblad B, Engström G, Hamrefors V, Manjer J, et al. Gene variance in the nicotinic receptor cluster (CHRNA5-CHRNA3-CHRNB4) predicts death from cardiopulmonary disease and cancer in smokers. J Intern Med 2016; 279(4): 388-98.
Bierut LJ, Stitzel JA, Wang JC, Hinrichs AL, Grucza RA, Xuei X, et al. Variants in nicotinic receptors and risk for nicotine dependence. Am J Psychiatry 2008; 165(9): 1163-71.
Cameli C, Bacchelli E, De Paola M, Giucastro G, Cifiello S, Collo G, et al. Genetic variation in CHRNA7 and CHRFAM7A is associated with nicotine dependence and response to varenicline treatment. Eur J Hum Genet 2018.
Ware JJ, van den Bree MB, Munafò MR. Association of the CHRNA5-A3-B4 gene cluster with heaviness of smoking: A meta-analysis. Nicotine Tob Res 2011; 1 3(12): 1167-75.
Munafò MR, Timofeeva MN, Morris RW, Prieto-Merino D, Sattar N, Brennan P, et al. Association between genetic variants on chromosome 15q25 locus and objective measures of tobacco exposure. J Natl Cancer Inst 2012; 104(10): 740-8.
Barrie ES, Hartmann K, Lee SH, Frater JT, Seweryn M, Wang D, et al. The CHRNA5/CHRNA3/CHRNB4 nicotinic receptor regulome: Genomic architecture, regulatory variants, and clinical associations. Hum Mutat 2017; 38(1): 112-9.
Johnson EO, Chen LS, Breslau N, Hatsukami D, Robbins T, Saccone NL, et al. Peer smoking and the nicotinic receptor genes: An examination of genetic and environmental risks for nicotine dependence. Addiction 2010; 105(11): 2014-22.
Conlon MS, Bewick MA. Single nucleotide polymorphisms in CHRNA5 rs16969968, CHRNA3 rs578776, and LOC123688 rs8034191 are associated with heaviness of smoking in women in Northeastern Ontario, Canada. Nicotine Tob Res 2011; 13(11): 1076-83.
Pérez‐Morales R, González‐Zamora A, González‐Delgado MF, Calleros Rincón EY, Olivas Calderón EH, Martínez‐Ramírez OC, et al. CHRNA3 rs1051730 and CHRNA5 rs16969968 polymorphisms are associated with heavy smoking, lung cancer, and chronic obstructive pulmonary disease in a mexican population. Ann Hum Genet 2018; 82(6): 415-24.
Byun J, Schwartz AG, Lusk C, Wenzlaff AS, de Andrade M, Mandal D, et al. Genome-wide association study of familial lung cancer. Mol Carcinog 2018; 39(9): 113540.
Korytina GF, Akhmadishina LZ, Viktorova EV, Kochetova OV, Viktorova TV. IREB2, CHRNA5, CHRNA3, FAM13A & hedgehog interacting protein genes polymorphisms & risk of chronic obstructive pulmonary disease in Tatar population from Russia. Indian J Med Res 2016; 144(6): 865-76.
Pintarelli G, Cotroneo CE, Noci S, Dugo M, Galvan A, Delli Carpini S, et al. Genetic susceptibility variants for lung cancer: Replication study and assessment as expression quantitative trait loci. Sci Rep 2017; 7: 42185-92.
Hobbs BD, Parker MM, Chen H, Lao T. Hardin M2, Qiao D, et al. Exome array analysis identifies a common variant in IL27 associated with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2016; 194(1): 48-57.
Wang J, Liu Q, Yuan S, Xie W, Liu Y, Xiang Y, et al. Genetic predisposition to lung cancer: Comprehensive literature integration, meta-analysis, and multiple evidence assessment of candidate-gene association studies. Sci Rep 2017; 7(1): 8371-8.
Stephens SH, Hartz SM, Hoft NR, Saccone NL, Corley RC, Hewitt JK, et al. Distinct loci in the CHRNA5/CHRNA3/CHRNB4 gene cluster are associated with onset of regular smoking. Genet Epidemiol 2013; 3788): 846-59.
Gu M, Dong X, Zhang X, Wang X, Qi Y, Yu J, et al. Strong association between two polymorphisms on 15q25.1 and lung cancer risk: A meta-analysis. PLoS One 2012; 7(6): e37970-5.
Chen LS, Baker TB, Piper ME, Breslau N, Cannon DS, Doheny KF, et al. Interplay of genetic risk factors (CHRNA5-CHRNA3- CHRNB4) and cessation treatments in smoking cessation success. Am J Psychiatry 2012; 16987): 735-42.
Hartz SM, Short SE, Saccone NL, Culverhouse R, Chen L, Schwantes-An TH, et al. Increased genetic vulnerability to smoking at CHRNA5 in early-onset smokers. Arch Gen Psychiatry 2012; 69(8): 854-60.
Matsson H, Söderhäll C, Einarsdottir E, Lamontagne M, Gudmundsson S, Backman H, et al. Targeted high-throughput sequencing of candidate genes for chronic obstructive pulmonary disease. BMC Pulm Med 2016; 16(1): 146-52.
Zhao Z, Jiang C, Zhao D, Li Y, Liang C, Liu W, et al. Two CHRN susceptibility variants for COPD are genetic determinants of emphysema and chest computed tomography manifestations in Chinese patients. Int J Chron Obstruct Pulmon Dis 2017; 12: 1447-55.
Chen LS, Bach RG, Lenzini PA, Spertus JA, Bierut LJ, Cresci S. CHRNA5 variant predicts smoking cessation in patients with acute myocardial infarction. Nicotine Tob Res 2014; 16(9): 1224-31.
Broms U, Wedenoja J, Largeau MR, Korhonen T, Pitkäniemi J, Keskitalo-Vuokko K, et al. Analysis of detailed phenotype profiles reveals CHRNA5-CHRNA3-CHRNB4 gene cluster association with several nicotine dependence traits. Nicotine Tob Res 2012; 14(6): 720-33.
Culverhouse RC, Johnson EO, Breslau N, Hatsukami DK, Sadler B, Brooks AI, et al. Multiple distinct CHRNB3-CHRNA6 variants are genetic risk factors for nicotine dependence in African Americans and European Americans. Addiction 2014; 109(5): 814-22.
Sadler B, Haller G, Agrawal A, Culverhouse R, Bucholz K, Brooks A, et al. Variants near CHRNB3-CHRNA6 are associated with DSM-5 cocaine use disorder: evidence for pleiotropy. Sci Rep 2014; 4: 4497-105.
Wang SD, van der Vaart A, Xu Q, Seneviratne C, Pomerleau OF, Pomerleau CS, et al. Significant associations of CHRNA2 and CHRNA6 with nicotine dependence in European American and African American populations. Hum Genet 2014; 133: 575-86.
Zeiger JS, Haberstick BC, Schlaepfer I, Collins AC, Corley RP, Crowley TJ, et al. The neuronal nicotinic receptor subunit genes (CHRNA6 and CHRNB3) are associated with subjective responses to tobacco. Hum Mol Genet 2008; 17(5): 724-34.
Cui WY, Wang S, Yang J, Yi SG, Yoon D, Kim YJ, et al. Significant association of CHRNB3 variants with nicotine dependence in multiple ethnic populations. Mol Psychiatry 2013; 18(11): 1149-51.
Bar-Shira A, Gana-Weisz M, Gan-Or Z, Giladi E, Giladi N, Orr-Urtreger A. CHRNB3 c.-57A>G functional promoter change affects Parkinson’s disease and smoking. Neurobiol Aging 2014; 35(9): 2179.e1-6.
Ehringer MA, McQueen MB, Hoft NR, Saccone NL, Stitzel JA, Wang JC, et al. Association of CHRN genes with “dizziness” to tobacco. Am J Med Genet B Neuropsychiatr Genet 2010; 153B(2): 600-9.
Wang SD, van der Vaart A, Xu Q, Seneviratne C, Pomerleau OF, Pomerleau CS, et al. Significant associations of CHRNA2 and CHRNA6 with nicotine dependence in European American and African American populations. Hum Genet 2014; 133(5): 575-86.
McKay JD, Hung RJ, Han Y, Zong X, Carreras-Torres R, Christiani DC, et al. Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes. Nat Genet 2017; 49(7): 1126-32.
Byun J, Schwartz AG, Lusk C, Wenzlaff AS, de Andrade M, Mandal D, et al. Genome-wide association study of familial lung cancer. Carcinogenesis 2018; 39(9): 1135-40.
Gault J, Robinson M, Berger R, Drebing C, Logel J, Hopkins J, et al. Genomic organization and partial duplication of the human alpha7 neuronal nicotinic acetylcholine receptor gene (CHRNA7). Genomics 1998; 52(2): 173-85.
Riley B, Williamson M, Collier D, Wilkie H, Makoff AA. 3-Mb map of a large segmental duplication overlapping the alpha 7-nicotinic acetylcholine receptor gene (CHRNA7) at human 15q13-q14. Genomics 2002; 79(2): 197-209.
Locke DP, Archidiacono N, Misceo D, Cardone MF, Deschamps S, Roe B, et al. Refinement of a chimpanzee pericentric inversion breakpoint to a segmental duplication cluster. Genome Biol 2003; 4(8): R50-9.
Villiger Y, Szanto I, Jaconi S, Blanchet C, Buisson B, Krause KH, et al. Expression of an alpha7 duplicate nicotinic acetylcholine receptor-related protein in human leukocytes. J Neuroimmunol 2002; 126(1-2): 86-98.
van Maanen MA, Stoof SP, van der Zanden EP, de Jonge WJ, Janssen RA, Fischer DF, et al. The alpha7 nicotinic acetylcholine receptor on fibroblast-like synoviocytes and in synovial tissue from rheumatoid arthritis patients: A possible role for a key neurotransmitter in synovial inflammation. Arthritis Rheum 2009; 60(5): 1272-81.
de Lucas-Cerrillo AM, Maldifassi MC, Arnalich F, Renart J, Atienza G, Serantes R, et al. Function of partially duplicated human α7 nicotinic receptor subunit CHRFAM7A gene: Potential implications for the cholinergic anti-inflammatory response. J Biol Chem 2011; 286(1): 594-606.
Flomen RH, Shaikh M, Walshe M, Schulze K, Hall MH, Picchioni M, et al. Association between the 2-bp deletion polymorphism in the duplicated version of the alpha7 nicotinic receptor gene and P50 sensory gating. Eur J Hum Genet 2013; 21(1): 76-81.
Drisdel RC, Green WN. Neuronal alpha-bungarotoxin receptors are alpha7 subunit homomers. J Neurosci 2000; 20(1): 133-9.
Kabbani N, Nichols RA. Beyond the channel: Metabotropic signaling by nicotinic receptors. Trends Pharmacol Sci 2018; 39(4): 354-66.
Russo P, Taly A. α7-Nicotinic acetylcholine receptors: An old actor for new different roles. Curr Drug Targets 2012; 13(5): 574-8.
Andersen N, Corradi J, Sine SM, Bouzat C. Stoichiometry for activation of neuronal α7 nicotinic receptors. Proc Natl Acad Sci USA 2013; 110(51): 20819-24.
Wu J, Liu Q, Tang P, et al. Heteromeric α7β2 nicotinic acetylcholine receptors in the brain. Trends Pharmacol Sci 2016; 37(7): 562-74.
Papke RL, Porter Papke JK. Comparative pharmacology of rat and human alpha7 nAChR condnucted with net charge analysis. Br J Pharmacol 2002; 137(1): 49-61.
Williams DK, Peng C, Kimbrell MR, Papke RL. Intrinsically low open probability of α7 nicotinic acetylcholine receptors can be overcome by positive allosteric modulation and serum factors leading to the generation of excitotoxic currents at physiological temperatures. Mol Pharmacol 2012; 82(4): 746-59.
Li P, Steinbach JH. The neuronal nicotinic α4β2 receptor has a high maximal probability of being open. Br J Pharmacol 2010; 160(8): 1906-15.
Lansdell SJ, Gee VJ, Harkness PC, Doward AI, Baker ER, Gibb AJ, et al. RIC-3 enhances functional expression of multiple nicotinic acetylcholine receptor subtypes in mammalian cells. Mol Pharmacol 2005; 68(5): 1431-8.
Alexander JK, Sagher D, Krivoshein AV, Criado M, Jefford G, Green WN. Ric-3 promotes alpha7 nicotinic receptor assembly and trafficking through the ER subcompartment of dendrites. J Neurosci 2010; 30(30): 10112-26.
Halevi S, Yassin L, Eshel M, Sala F, Sala S, Criado M, et al. Conservation within the RIC-3 gene family: effectors of mammalian nicotinic acetylcholine receptor expression. J Biol Chem 2003; 278(36): 34411-7.
Matta JA, Gu S, Davini WB, Lord B, Siuda ER, Harrington AW, et al. NACHO Mediates Nicotinic Acetylcholine Receptor Function throughout the Brain. Cell Rep 2017; 19(4): 688-96.
Kuryatov A, Mukherjee J, Lindstrom J. Chemical chaperones exceed the chaperone effects of RIC-3 in promoting assembly of functional α7 AChRs. PLoS One 2013; 8(4): e62246-52.
Drisdel RC, Manzana E, Green WN. The role of palmitoylation in functional expression of nicotinic alpha7 receptors. J Neurosci 2004; 24(46): 10502-10.
Li S, Nai Q, Lipina TV, Roder JC, Liu F. α7nAchR/NMDAR coupling affects NMDAR function and object recognition. Mol Brain 2013; 20(6): 58-67.
Zhang H, Li T, Li S, Liu F. Cross-talk between α7 nAchR and NMDAR revealed by protein profiling. J Proteomics 2016; 131: 113-21.
Yang Y, Paspalas CD, Jin LE, Picciotto MR, Arnsten AF, Wang M. Nicotinic α7-receptors enhance NMDA cognitive circuits in dorsolateral prefrontal cortex. Proc Natl Acad Sci USA 2013; 110(29): 12078-83.
Lozada AF, Wang X, Gounko NV, Massey KA, Duan J, Liu Z, et al. Glutamatergic synapse formation is promoted by α7-containing nicotinic acetylcholine receptors. J Neurosci 2012; 32(22): 7651-61.
Lyukmanova EN, Shulepko MA, Buldakova SL, Kasheverov IE, Shenkarev ZO, Reshetnikov RV, et al. Water-soluble LYNX1 residues important for interaction with muscle-type and/or neuronal nicotinic receptors. J Biol Chem 2013; 288(22): 15888-99.
Slominski A. Nicotinic receptor signaling in nonexcitable epithelial cells: Paradigm shifting from ion current to kinase cascade. Focus on “Upregulation of nuclear factor-kappaB expression by SLURP-1 is mediated by alpha7-nicotinic acetylcholine receptor and involves both ionic events and activation of protein kinases”. Am J Physiol Cell Physiol 2010; 299(5): C885-7.
Kawashima K, Fujii T, Moriwaki Y, Misawa H, Horiguchi K. Non-neuronal cholinergic system in regulation of immune function with a focus on α7 nAChRs. Int Immunopharmacol 2015; 29(1): 127-34.
Vanfleteren LE, Spruit MA, Wouters EF, Franssen FM. Management of chronic obstructive pulmonary disease beyond the lungs. Lancet Respir Med 2016; 4(11): 911-24.
Global Strategy For The Diagnosis, Management, And Prevention Of Chronic Obstructive Pulmonary Disease. 2017;
Decramer M, Janssens W, Miravitlles M. Chronic obstructive pulmonary disease. Lancet 2012; 379(9823): 1341-51.
Agustí A, Faner R. COPD beyond smoking: New paradigm, novel opportunities. Lancet Respir Med 2018; 6(5): 324-6.
Kawashima K, Fujii T, Moriwaki Y, Misawa H, Horiguchi K. Non-neuronal cholinergic system in regulation of immune function with a focus on α7 nAChRs. Int Immunopharmacol 2015; 29(1): 127-34.
Lam DC, Luo SY, Fu KH, Lui MM, Chan KH, Wistuba II, et al. Nicotinic acetylcholine receptor expression in human airway correlates with lung function. Am J Physiol Lung Cell Mol Physiol 2016; 310(3): L232-9.
Nastrucci C, Cesario A, Russo P. α7 nAChR in airway respiratory epithelial cells. Curr Drug Targets 2012; 13(5): 666-70.
Maouche K, Medjber K, Zahm JM, Delavoie F, Terryn C, Coraux C, et al. Contribution of α7 nicotinic receptor to airway epithelium dysfunction under nicotine exposure. Proc Natl Acad Sci USA 2013; 110(10): 4099-104.
Maouche K, Polette M, Jolly T, Medjber K, Cloëz-Tayarani I, Changeux JP, et al. Alpha7 nicotinic acetylcholine receptor regulates airway epithelium differentiation by controlling basal cell proliferation. Am J Pathol 2009; 175(5): 1868-82.
Gundavarapu S, Wilder JA, Mishra NC, Rir-Sima-Ah J, Langley RJ, Singh SP, et al. Role of nicotinic receptors and acetylcholine in mucous cell metaplasia, hyperplasia, and airway mucus formation in vitro and in vivo. J Allergy Clin Immunol 2012; 130(3): 770-80.
Yang L, Lu X, Qiu F, Fang W, Zhang L, Huang D, et al. Duplicated copy of CHRNA7 increases risk and worsens prognosis of COPD and lung cancer. Eur J Hum Genet 2015; 23(8): 1019-24.
Maneckjee R, Minna JD. Opioid and nicotine receptors affect growth regulation of human lung cancer cell lines. Proc Natl Acad Sci USA 1990; 87(9): 3294-8.
Kummer W, Krasteva-Christ G. Non-neuronal cholinergic airway epithelium biology. Curr Opin Pharmacol 2014; 16: 43-9.
Paleari L, Grozio A, Cesario A, Russo P. The cholinergic system and cancer. Semin Cancer Biol 2008; 18(3): 211-7.
Schuller HM. Is cancer triggered by altered signalling of nicotinic acetylcholine receptors? Nat Rev Cancer 2009; 9(3): 195-205.
Catassi A, Servent D, Paleari L, Cesario A, Russo P. Multiple roles of nicotine on cell proliferation and inhibition of apoptosis: implications on lung carcinogenesis. Mutat Res 2008; 659(3): 221-31.
Wang S, Hu Y. α7 nicotinic acetylcholine receptors. Oncol Lett 2018; 1 6(2): 1375-82.
Schuller HM. Regulatory role of the α7nAChR in cancer. Curr Drug Targets 2012; 13(5): 680-7.
Russo P, Cardinale A, Margaritora S, Cesario A. Nicotinic receptor and tobacco-related cancer. Life Sci 2012; 91(21-22): 1087-92.
Mucchietto V, Crespi A, Fasoli F, Clementi F, Gotti C. Neuronal acetylcholine nicotinic receptors as new targets for lung cancer treatment. Curr Pharm Des 2016; 22(14): 2160-9.
Wang S, Hu Y. α7-nicotinic acetylcholine receptors in lung cancer. Oncol Lett 2018; 16(2): 1375-82.
Russo P, Cardinale A, Shuller H. A new “era” for the α7-nAChR. Curr Drug Targets 2012; 13(5): 721-5.
Viswanath K, Herbst RS, Land SR, Leischow SJ, Shields PG. Writing Committee for the AACR Task Force on Tobacco and cancer: An American Association for Cancer Research policy statement. Cancer Res 2010; 70(9): 3419-30.
Matta SG, Balfour DJ, Benowitz NL, Boyd RT, Buccafusco JJ, Caggiula AR, et al. Guidelines on nicotine dose selection for in vivo research. Psychopharmacol 2007; 190(3): 269-319.
GBD 2015 Risk Factors Collaborators. Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: A systematic analysis for the Global Burden of Disease Study 2015. Lancet 2016; 388(10053): 1659-724.
GBD 2015 Tobacco Collaborators. Smoking prevalence and attributable disease burden in 195 countries and territories, 1990-2015: A systematic analysis from the Global Burden of Disease Study 2015. Lancet 2017 May 13; 389(10082): 1885-906.
Mannino DM, Buist AS. Global burden of COPD: Risk factors, prevalence, and future trends. Lancet 2007; 370(9589): 765-73.
GBD 2016 Risk Factors Collaborators. Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet 2017; 390(10100): 1345-422.
Salvi SS, Barnes PJ. Chronic obstructive pulmonary disease in non-smokers. Lancet 2009; 374(9691): 733-43.
Alwan A. Global Status Report on Non-Communicable Diseases. WHO 2010.
Alicandro G, Sebastiani G, Bertuccio P, Zengarini N, Costa G. La Vecchia, et al. The main causes of death contributing to absolute and relative socio-economic inequality in Italy. Public Health 2018; 164: 39-48.
Celli BR. Pharmacological Therapy of COPD: Reasons for Optimism. Chest 2018; S0012-3692(18): 31061-4.
Spruit MA, Singh SJ, Garvey C, ZuWallack R, Nici L, Rochester C, et al. Smoking cessation is the most important treatment for smokers with COPD An official American Thoracic Society/European Respiratory Society statement: Key concepts and advances in pulmonary rehabilitation. Am J Respir Crit Care Med 2013; 188(8): e13-64.
van Eerd EA, van der Meer RM, van Schayck OC, Kotz D. Smoking cessation for people with chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2016; (8): CD010744.
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68(6): 394-424.
Ferlay J, Colombet M, Soerjomataram I, Dyba T, Randi G, Bettio M, et al. Cancer incidence and mortality patterns in Europe: Estimates for 40 countries and 25 major cancers in 2018. Eur J Cancer 2018; S0959-8049(18): 30955-9.
de Groot PM, Wu CC, Carter BW, Munden RF. The epidemiology of lung cancer. Transl Lung Cancer Res 2018; 7(3): 22033-9.
Mazières J, Pujol JL, Kalampalikis N, Bouvry D, Quoix E, Filleron T, et al. Perception of lung cancer among the general population and comparison with other cancers. J Thorac Oncol 2015; 10(3): 420-5.
Greillier L, Cortot AB, Viguier J, Brignoli-Guibaudet L, Lhomel C, Eisinger F, et al. Perception of lung cancer risk: Impact of smoking status and nicotine dependence. Curr Oncol Rep 2018; 20(Suppl. 1): 18-25.
Menezes AM, Landis SH, Han MK, Muellerova H, Aisanov Z, van der Molen T, et al. Continuing to confront COPD International Surveys: Comparison of patient and physician perceptions about COPD risk and management. Int J Chron Obstruct Pulmon Dis 2015; 10: 159-72.
Ziebarth NR. Lung cancer risk perception biases. Prev Med 2018; 110: 16-23.
Rojewski AM, Tanner NT, Dai L, Ravenel JG, Gebregziabher M, Silvestri GA, et al. Tobacco dependence predicts higher lung cancer and mortality rates and lower rates of smoking cessation in the national lung screening trial. Chest 2018; 154(1): 110-8.
Paliwal A, Vaissière T, Krais A, Cuenin C, Cros MP, Zaridze D, et al. Aberrant DNA methylation links cancer susceptibility locus 15q25.1 to apoptotic regulation and lung cancer. Cancer Res 2010; 70(7): 2779-88.
Ji X, Bossé Y, Landi MT, et al. Identification of susceptibility pathways for the role of chromosome 15q25.1 in modifying lung cancer risk. Nat Commun 2018; 9(1): 3221.
Nedeljkovic I, Carnero-Montoro E, Lahousse L, van der Plaat DA, de Jong K, Vonk JM, et al. Understanding the role of the chromosome 15q25.1 in COPD through epigenetics and transcriptomics. Eur J Hum Genet 2018; 26(5): 709-22.
Houfek J. Smokers' response to nicotine dependence genotyping. Identifier. NCT01780038 (2013)
Sofuoglu M. Sensitivity to intravenous nicotine: Genetic moderators. Identifier. NCT00969137 (2009)
Heishman SJ. Nicotine reinforcement and smoking-cue reactivity: Association with genetic polymorphisms Identifier. NCT01505725. (2012)
Stein E. The impact of genetic variation in nicotinic cholinergic receptors on functional brain networks underlying addiction susceptibilityClinicalTrialsgov Identifier: NCT01924468 (2013)
Nichols J. A Protocol for an randomised controlled trial of smoking cessation success rate with or without a genetic test, "Respiragene", to assess lung cancer risk: An exploratory study. Identifier: NCT01176383 (2010)
Schaal C, Chellappan S. Nicotine-mediated regulation of nicotinic acetylcholine receptors in non-small cell lung adenocarcinoma by E2F1 and STAT1 transcription factors. PLoS One 2016; 11(5): e0156451-.

© 2022 Bentham Science Publishers | Privacy Policy