Genetic variants of CHRNA5-A3 and CHRNB3-A6 predict survival of patients with advanced non-small cell lung cancer

Nicotinic acetylcholine receptors (nAChRs) play a key role in carcinogenesis and progression of lung cancer; and polymorphisms in CHRNA5-A3 and CHRNB3-A6, two gene clusters encoding nAChR subunits, have been associated with lung cancer risk. In this study, we investigated whether variants in the two...

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Bibliographic Details
Published in:Oncotarget 2016-05, Vol.7 (18), p.26436-26443
Main Authors: Wang, Yang, Peng, Xiaonu, Zhu, Lijun, Hu, Likuan, Song, Yipeng
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Asian Continental Ancestry Group - genetics
Carcinoma, Non-Small-Cell Lung - genetics
Carcinoma, Non-Small-Cell Lung - mortality
Disease-Free Survival
Female
Genetic Predisposition to Disease
Genotype
Humans
Kaplan-Meier Estimate
Lung Neoplasms - genetics
Lung Neoplasms - mortality
Male
Middle Aged
Nerve Tissue Proteins - genetics
Polymorphism, Single Nucleotide
Proportional Hazards Models
Receptors, Nicotinic - genetics
Research Paper
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Summary:Nicotinic acetylcholine receptors (nAChRs) play a key role in carcinogenesis and progression of lung cancer; and polymorphisms in CHRNA5-A3 and CHRNB3-A6, two gene clusters encoding nAChR subunits, have been associated with lung cancer risk. In this study, we investigated whether variants in the two gene clusters were associated with prognosis of advanced non-small cell lung cancer (NSCLC). A total of 165 stage IIIB-IV NSCLC patients were enrolled in this study. Three polymorphisms (rs667282 and rs3743073 in CHRNA5-A3 and rs13280604 in CHRNB3-A6) were genotyped using the TaqMan method. Overall survival (OS) was estimated using the log-rank test and the Cox models. Our results showed that patients with CHRNA5-A3 rs667282 TT or TC genotypes had a significantly shorter OS than those carrying the CC genotype (Log-rank, P = 0.043). Furthermore, multivariate Cox regression analysis showed that rs667282 TT/TC genotypes are significantly associated with increased risk of overall deaths (adjusted hazard ratio, 1.7; 95% CI, 1.1-2.7). However, the similar results were not observed for other two polymorphisms. Furthermore, no evident association was found between these variants and clinicopathologic features of advanced NSCLC. Our present study suggested that rs667282 in CHRNA5-A3 may modify the prognosis of patients with advanced NSCLC.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.8510