Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Molecular Diversity Preservation International (MDPI) 2014
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
_version_ 1782315075949821952
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
work_keys_str_mv AT heping chrna3polymorphismmodifieslungadenocarcinomariskinthechinesehanpopulation
AT yangxuexi chrna3polymorphismmodifieslungadenocarcinomariskinthechinesehanpopulation
AT hexuanqiu chrna3polymorphismmodifieslungadenocarcinomariskinthechinesehanpopulation
AT chenjun chrna3polymorphismmodifieslungadenocarcinomariskinthechinesehanpopulation
AT lifenxia chrna3polymorphismmodifieslungadenocarcinomariskinthechinesehanpopulation
AT guxia chrna3polymorphismmodifieslungadenocarcinomariskinthechinesehanpopulation
AT jiangjuhong chrna3polymorphismmodifieslungadenocarcinomariskinthechinesehanpopulation
AT lianghuiying chrna3polymorphismmodifieslungadenocarcinomariskinthechinesehanpopulation
AT yaoguangyu chrna3polymorphismmodifieslungadenocarcinomariskinthechinesehanpopulation
AT hejianxing chrna3polymorphismmodifieslungadenocarcinomariskinthechinesehanpopulation