Abstract
CHRNA5/CHRNA3/CHRNB4 gene cluster is located on chromosome 15q25.1 and was reported to be associated with risk of lung cancer. So far, the effect of three single nucleotide polymorphisms rs6495309, rs8040868, rs1948 in this gene cluster was unclear about lung cancer risk. The aim of the present study was to evaluate the associations of rs6495309, rs8040868, rs1948 polymorphism, smoking exposure and the interaction with non-small cell lung cancer risk in Chinese population. In this hospital-based case-control study, 306 lung cancer patients and 306 cancer-free controls were interviewed to collect demographic data and exposure status of smoking, and then donate 2ml venous blood which was used to be genotyped by Taqman allelic discrimination method. Our study found that subjects carrying rs1948 CT genotype stated to be a risk factor in Chinese Han population (adjusted OR = 1.594, 95% CI = 1.066-2.383, P = 0.023) and in non-smoking population (adjusted OR = 1.896, 95%CI = 1.069–3.362, P = 0.029). rs8040868 CC genotype indicated a higher risk for lung cancer in non-smokers in a recessive model (adjusted OR = 2.496, 95%CI = 1.044–5.965, P = 0.040) and in age-based stratified analysis (age <= 60, adjusted OR = 4.213, 95%CI = 1.062-16.708, P = 0.041). All smoking interaction were positive in the multiplicative interaction of the SNPs and smoking status (-/+) compared with recessive model. Overall, these finding suggested that rs1948(C > T) and rs8040868(T > C) could be meaningful as genetic markers for lung cancer risk in Chinese Han population.
Highlights
Lung cancer is the leading cause of cancer-related death and the most common cancer worldwide [1, 2]
Neuronal nicotinic acetylcholine receptor gene cluster (CHRNA5/CHRNA3/CHRNB4) on www.impactjournals.com/oncotarget chromosome 15q25.1 belongs to the ligand-gated ion channel superfamily which widely distributing in the brain that binds the ligands acetylcholine and nicotine [7], which mediates fast cholinergic synaptic transmission, involving in activation of downstream signaling networks that promote cell proliferation, migration, invasion, and angiogenesis [8]. nAChRs have been considered to be associated with nicotine dependence and smoking behaviors as well as chronic obstructive pulmonary disease (COPD) and lung cancer risk [9]
For all single nucleotide polymorphisms (SNPs), the distribution of genotypes among the control subjects was in accordance with Hardy–Weinberg equilibrium, which suggested that our control group has an appropriate representativeness for the studying population
Summary
Lung cancer is the leading cause of cancer-related death and the most common cancer worldwide [1, 2]. Genome-wide association studies (GWAS) have highlighted the prevailing view that smoking quantity and frequency as a proxy for nicotine dependence is most associated with single nucleotide polymorphisms (SNPs) at the CHRNA5/CHRNA3/CHRNB4 gene cluster [5]. Activation of nAChRs suppresses cell apoptosis and stimulates the growth of lung cancer cells, which indicates that nicotine can lead to lung cancer development by acting as tumor promoters that results in the outgrowth of cells with genetic damage [6]. Neuronal nicotinic acetylcholine receptor (nAChR) gene cluster (CHRNA5/CHRNA3/CHRNB4) on www.impactjournals.com/oncotarget chromosome 15q25.1 belongs to the ligand-gated ion channel superfamily which widely distributing in the brain that binds the ligands acetylcholine and nicotine [7], which mediates fast cholinergic synaptic transmission, involving in activation of downstream signaling networks that promote cell proliferation, migration, invasion, and angiogenesis [8]. Neuronal nicotinic acetylcholine receptor (nAChR) gene cluster (CHRNA5/CHRNA3/CHRNB4) on www.impactjournals.com/oncotarget chromosome 15q25.1 belongs to the ligand-gated ion channel superfamily which widely distributing in the brain that binds the ligands acetylcholine and nicotine [7], which mediates fast cholinergic synaptic transmission, involving in activation of downstream signaling networks that promote cell proliferation, migration, invasion, and angiogenesis [8]. nAChRs have been considered to be associated with nicotine dependence and smoking behaviors as well as chronic obstructive pulmonary disease (COPD) and lung cancer risk [9]
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