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CHRNA3 Polymorphism Modifies Lung Adenocarcinoma Risk in the Chinese Han Population
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, rs...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Molecular Diversity Preservation International (MDPI)
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4013574/ https://www.ncbi.nlm.nih.gov/pubmed/24686516 http://dx.doi.org/10.3390/ijms15045446 |
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author | 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 |
author_facet | 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 |
author_sort | He, Ping |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4013574 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Molecular Diversity Preservation International (MDPI) |
record_format | MEDLINE/PubMed |
spelling | pubmed-40135742014-05-08 CHRNA3 Polymorphism Modifies Lung Adenocarcinoma Risk in the Chinese Han Population 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 Int J Mol Sci Article 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. Molecular Diversity Preservation International (MDPI) 2014-03-28 /pmc/articles/PMC4013574/ /pubmed/24686516 http://dx.doi.org/10.3390/ijms15045446 Text en © 2014 by the authors; licensee MDPI, Basel, Switzerland http://creativecommons.org/licenses/by/3.0/ This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Article 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 CHRNA3 Polymorphism Modifies Lung Adenocarcinoma Risk in the Chinese Han Population |
title | CHRNA3 Polymorphism Modifies Lung Adenocarcinoma Risk in the Chinese Han Population |
title_full | CHRNA3 Polymorphism Modifies Lung Adenocarcinoma Risk in the Chinese Han Population |
title_fullStr | CHRNA3 Polymorphism Modifies Lung Adenocarcinoma Risk in the Chinese Han Population |
title_full_unstemmed | CHRNA3 Polymorphism Modifies Lung Adenocarcinoma Risk in the Chinese Han Population |
title_short | CHRNA3 Polymorphism Modifies Lung Adenocarcinoma Risk in the Chinese Han Population |
title_sort | chrna3 polymorphism modifies lung adenocarcinoma risk in the chinese han population |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4013574/ https://www.ncbi.nlm.nih.gov/pubmed/24686516 http://dx.doi.org/10.3390/ijms15045446 |
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