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Int. J. Mol. Sci. 2014, 15(4), 5446-5457; doi:10.3390/ijms15045446
Article

CHRNA3 Polymorphism Modifies Lung Adenocarcinoma Risk in the Chinese Han Population

1,†
, 2,†
, 3,†
, 4,†
, 5
, 1
, 1
, 6
, 4
 and 7,8,*
1 Department of Pathology, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China 2 School of Biotechnology, Southern Medical University, Guangzhou 510515, China 3 The First Clinical College, Southern Medical University, Guangzhou 510515, China 4 Breast Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China 5 Da An Gene Co., Ltd. of Sun Yat-sen University, Guangzhou 510665, China 6 Department of Primary Public Health, Guangzhou Center for Disease Control and Prevention, Guangzhou 510440, China 7 Department of Cardiothoracic Surgery, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China 8 State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 20 January 2014 / Revised: 10 March 2014 / Accepted: 18 March 2014 / Published: 28 March 2014
(This article belongs to the Section Bioinorganic Chemistry)
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Abstract

Recent genome-wide association studies (GWASs) have identified 15q25.1 as a lung cancer susceptibility locus. Here, we sought to explore the direct carcinogenic effects of genetic variants in this region on the risk of developing lung adenocarcinoma (ADC). Five common SNPs (rs8034191, rs16969968, rs1051730, rs938682, and rs8042374) spanning the 15q25.1 locus were assayed in a case-control study examining a cohort of 301 lung ADCs and 318 healthy controls. Stratification analysis by gender, smoking status, and tumor, node, metastasis (TNM) classification, was performed. In addition, sections from ADC tissue and normal tissue adjacent to tumors were stained with an anti-CHRNA3 (cholinergic receptor nicotinic α3) antibody by immunohistochemistry in 81 cases. Our results demonstrate that rs8042374, a variant of the CHRNA3 gene, is associated with an increased risk of ADC with an OR of 1.76 (95% CI: 1.17–2.65, p = 0.024). This variant was linked to a greater risk of ADC in female nonsmokers (OR (95% CI): 1.81 (1.05–3.12), p = 0.032) and female stage I + II cases (OR (95% CI): 1.92 (1.03–3.57), p = 0.039). Although located within the same gene, rs938682 showed protective effects for smokers, stage III + IV cases, and male stage III + IV cases. Additionally, the CHRNA3 protein level in ADC tissue was slightly higher than in the surrounding normal lung tissue, based on immunohistochemical analysis. Our results suggest that the CHRNA3 polymorphism functions as a genetic modifier of the risk of developing lung ADC in the Chinese population, particularly in nonsmoking females.
Keywords: lung adenocarcinoma; single nucleotide polymorphism; CHRNA3; female nonsmokers lung adenocarcinoma; single nucleotide polymorphism; CHRNA3; female nonsmokers
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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He, P.; Yang, X.-X.; He, X.-Q.; Chen, J.; Li, F.-X.; Gu, X.; Jiang, J.-H.; Liang, H.-Y.; Yao, G.-Y.; He, J.-X. CHRNA3 Polymorphism Modifies Lung Adenocarcinoma Risk in the Chinese Han Population. Int. J. Mol. Sci. 2014, 15, 5446-5457.

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