Association of the CHRNA3 locus with lung cancer risk and prognosis in Chinese Han population

Abstract

Introduction: Recent genome-wide association studies in Caucasians revealed association with lung cancer risk of single nucleotide polymorphisms (SNPs) in the locus containing two nicotine acetylcholine receptor CHRNA genes. However, the reported risk SNPs are extremely rare in Asians. This study sought to identify other variants on CHRNA3 associated with lung cancer susceptibility and to explore whether SNPs of CHRNA3 are of prognostic factors in patients with non-small cell lung cancer (NSCLC) in Chinese Han population.

Methods: A case-control study of 529 cases and 567 controls was performed to study the association of three SNPs (rs3743076, rs3743078, and rs3743073) in CHRNA3 with lung cancer risk in Chinese Han population using logistic regression models. The relationship between CHRNA3 polymorphisms with overall survival among 122 patients with advanced stage (stage IIIb and IV) NSCLC were evaluated using Cox multiple model based on the International Association for the Study of Lung Cancer recommended tumor, node, metastasis new staging.

Results: Patients with genotypes TG or GG for the novel SNP rs3743073 in CHRNA3 gene, compared with those with TT, showed an increased risk of lung cancer (adjusted odds ratio = 1.91; 95% confidence interval, 1.38-2.63; p = 9.67 x 10) and worst survival (adjusted hazard ratio = 2.35; 95% confidence interval, 1.05-5.26; p = 0.04) in patients with advanced stage NSCLC based on International Association for the Study of Lung Cancer recommended tumor, node, metastasis new staging.

Conclusions: These results suggest that the rs3743073 polymorphism in CHRNA3 is predictive for lung cancer risk and prognostic in advanced stage NSCLC in Chinese Han population.