Nicotinic acetylcholine receptors and predisposition to lung cancer.
OBJECTIVE
To highlight the current body of knowledge regarding the role of nicotinic acetylcholine receptors (nAChRs) in lung cancer predisposition.


RESULTS
Smoking is a documented risk factor for cancer, especially for lung carcinomas. Nicotine and its derived carcinogenic nitrosamines contribute to lung cancer development and progression through the binding to nAChRs, which then activate proliferation, apoptosis, angiogenesis and tumour invasion. Recent genome-wide association studies have associated single nucleotide polymorphisms spanning the nAChR encoding genes cluster CHRNA3/A5/B4 with both nicotine dependence and lung cancer incidence and susceptibility. The α7 nAChR has also been implicated in the regulation of inflammation and immunity and, as a repressor of airway basal cell proliferation, α7 nAChR plays a role in the remodelling of the airway epithelium. Its decreased function may lead to squamous metaplasia and possibly the emergence of preneoplastic lesions.


CONCLUSIONS
nAChRs participate in the predisposition for preneoplastic lesions and the further emergence of lung carcinomas. More studies are needed to determine the influence of gene polymorphisms on nAChRs function and of nAChRs activation/desensitization on lung diseases, which represents a new stimulating approach in the understanding of lung tumorigenesis with potential clinical applications.
INSERM UMR-S 903, IFR 53, Université de Reims Champagne Ardenne, Reims, France. jm.tournier@univ-reims.fr
Jean-Marie
JM
Tournier
Philippe
P
Birembaut
D020022:Genetic Predisposition to Disease; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism*; D011110:Polymorphism, Genetic; D011230:Precancerous Conditions / Q000235:genetics / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000235:genetics* / Q000378:metabolism*
D011978:Receptors, Nicotinic