ABSTRACT
Lung cancer is the most frequent cancer among men in many countries. It is the result of interactions between genetic and environmental factors, among which tobacco smoking is a key environmental factor. CHRNA5, Cholinergic Receptor, Neuronal Nicotinic, Alpha Polypeptide-5, was previously reported to be associated with lung cancer risk. To identify the genetic susceptibility and tobacco smoking that influence lung cancer risk in Han population, we performed a case-control study in 228 patients and 301 controls. These data were compared using the χ(2)-test, genetic model analysis, and haplotype analysis. rs495956, rs680244, rs601079, rs555018, 588765 and rs11637635 showed an increased risk of lung cancer in both allelic model and genetic mode analysis. The genotype G/A-A/A of rs11637635 was most strongly associated with a 2.17-fold increased risk of lung cancer in dominant model (p = 0.018). One SNP, rs684513, was associated with a 0.645-fold decreased risk (p = 0.033) in allelic model analysis. By haplotype association analysis, haplotype sequences CTTATCAAAGA and GA of CHRNA5 were found to be associated with a 2.03-fold and 1.91-fold increased lung cancer risk (p < 0.05). Our results, combined with those from previous studies, suggest that genetic variation in CHRNA5 may influence susceptibility to lung cancer among Han smokers.
ABSTRACT
AIM AND METHODS: The effect of intrahippocampal microinjection of noradrenaline (NA) and its receptors antagonists and agonists on cellular immune functions were investigated in normal and adrenalectomy rat by determine the proliferative activity of Con A-stimulated splenic lymphocytes in MTT method and natural killer (NK) cell activity. RESULTS: (1) In normal group, the proliferative activity of Con A-Stimulated splenic lymphocytes were inhibited and the activity of NK cell were reduced with microinjection NA and beta1-, beta2-adrenergic receptor agonists Dobutamine (Dob, 4 microl, 6.0 x 10(-3) moL/L), Metaproterenol (Met, 4 microl, 8.0 x 10(-3) mol/L), compared with their intensity of effect, NA > Met > Dob; the immunosuppression effect induced by NA was partly hindered by alpha- and beta-receptor antagonists, phentolamine (Phen, 2 microl, 1.6 x 10(-2) mol/L) and propranolol (Prop, 2 microl, 1.6 x 10(-3) mol/L), and the action of Prop was more evident. (2) In adrenalectomy group, immunosuppression effect induced by NA was unconspicuous. CONCLUSION: The results suggested that NA in hippocampus could inhibit distinctly cellular immune functions, which was predominantly mediated by beta2- adrenergic receptor with a minor contribution of beta1- and alpha- adrenergic receptors. Moreover, keeping intact construction and function of adrenal gland have an important role in the effect of NA on cellular immune function.
