Research Papers:

Study on polymorphisms in CHRNA5/CHRNA3/CHRNB4 gene cluster and the associated with the risk of non-small cell lung cancer

Yiting Sun, Jiaye Li, Chang Zheng and Baosen Zhou _

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Oncotarget. 2018; 9:2435-2444. https://doi.org/10.18632/oncotarget.23459

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Yiting Sun1,3, Jiaye Li1,3, Chang Zheng2 and Baosen Zhou1,2

1Department of Clinical Epidemiology, First Affiliated Hospital, China Medical University, Shenyang, China

2Key Laboratory of Cancer Etiology and Prevention, China Medical University, Liaoning Provincial Department of Education, Liaoning, China

3First Clinical College, China Medical University, Shenyang, China

Correspondence to:

Baosen Zhou, email: [email protected]

Keywords: CHRNA5/CHRNA3/CHRNB4; single nucleotide polymorphism; non-small cell lung cancer; smoking; interaction

Received: March 24, 2017     Accepted: December 11, 2017     Published: December 20, 2017


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.

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