Neuronal acetylcholine receptor subunit alpha-9 (CHRNA9) polymorphisms are associated with NSCLC risk in a Chinese population

Abstract

Neuronal acetylcholine receptor subunit alpha-9 (CHRNA9) encodes a plasma membrane protein of divalent cation channels and is expressed in keratinocytes. This study aimed to investigate CHRNA9 single-nucleotide polymorphisms (SNPs) for association with non-small cell lung cancer (NSCLC), especially squamous cell carcinoma (SCC) risk, in a Chinese population. This case-control study included 500 NSCLC patients and 500 age-matched healthy controls. CHRNA9 rs56159866, rs6819385, rs55998310, and rs182073550 SNPs were genotyped and associated for NSCLC risk by computing the odds ratios (ORs) and 95 % confidence intervals (CIs) from multivariate unconditional logistic regression analyses with adjustment for age. The frequencies of the CHRNA9 rs6819385 G allele were 16.1, 15.2, and 20.8% in male NSCLC patients, male SCC patients, and male controls, respectively. The CHRNA9 rs6819385 A allele was associated with an increased risk of developing NSCLC (P = 0.04, OR = 1.37; 95% CI 1.02-1.83) and SCC (P = 0.04, OR = 1.47; 95% CI 1.01-2.13). The CHRNA9 rs6819385 A/A homozygote was associated with an increased risk of NSCLC and SCC in all patients (OR = 1.38; 95% CI 1.06-1.79; P = 0.02, and OR = 1.61; 95% CI 1.09-2.38; P = 0.02, respectively) and in male patients (OR = 1.57; 95% CI 1.11-2.21; P = 0.01, and OR = 1.70; 95% CI 1.11-2.61; P = 0.01, respectively), indicating that the CHRNA9 rs6819385 A/A homozygote had a 1.61-fold and 1.70-fold increased risk of developing lung SCC in all patients (95% CI 1.09-2.38, P = 0.02) and in males (95% CI 1.11-2.61, P = 0.01), respectively. The CHRNA9 rs6819385 SNP was significantly associated with an increased risk of NSCLC, especially for SCC in male patients in this Chinese population.