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

CHRNA3 Polymorphism Modifies Lung Adenocarcinoma Risk in the Chinese Han Population

1,†email, 2,†email, 3,†email, 4,†email, 5email, 1email, 1email, 6email, 4email and 7,8,* email
Received: 20 January 2014; in revised form: 10 March 2014 / Accepted: 18 March 2014 / Published: 28 March 2014
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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.
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
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MDPI and ACS Style

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.

AMA Style

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. International Journal of Molecular Sciences. 2014; 15(4):5446-5457.

Chicago/Turabian Style

He, Ping; Yang, Xue-Xi; He, Xuan-Qiu; Chen, Jun; Li, Fen-Xia; Gu, Xia; Jiang, Ju-Hong; Liang, Hui-Ying; Yao, Guang-Yu; He, Jian-Xing. 2014. "CHRNA3 Polymorphism Modifies Lung Adenocarcinoma Risk in the Chinese Han Population." Int. J. Mol. Sci. 15, no. 4: 5446-5457.

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