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Frequent Epigenetic Silencing of the p16 Gene in Non‐small Cell Lung Cancers of Tobacco Smokers
Epidemiological studies have demonstrated a causal link between tobacco smoking and lung cancer. We investigated the association between inactivation of the p16 gene and tobacco smoking in 51 non‐small cell lung cancers (NSCLCs). Aberrations of the p16 gene were studied by PCR single‐strand conforma...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Blackwell Publishing Ltd
2002
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5926878/ https://www.ncbi.nlm.nih.gov/pubmed/12417040 http://dx.doi.org/10.1111/j.1349-7006.2002.tb01212.x |
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author | Yanagawa, Naoki Tamura, Gen Oizumi, Hiroyuki Takahashi, Nobumasa Shimazaki, Yasuhisa Motoyama, Teiichi |
author_facet | Yanagawa, Naoki Tamura, Gen Oizumi, Hiroyuki Takahashi, Nobumasa Shimazaki, Yasuhisa Motoyama, Teiichi |
author_sort | Yanagawa, Naoki |
collection | PubMed |
description | Epidemiological studies have demonstrated a causal link between tobacco smoking and lung cancer. We investigated the association between inactivation of the p16 gene and tobacco smoking in 51 non‐small cell lung cancers (NSCLCs). Aberrations of the p16 gene were studied by PCR single‐strand conformation polymorphism analysis, followed by direct sequencing, microsatellite analysis, methylation‐specific PCR, and immunohistochemistry. Mutations were detected in 3.9% (2/51) of the tumors; the tumors carrying mutations were from smokers. The incidences of loss of heterozygosity, homozygous deletion, and promoter methylation in 37 smokers vs. 14 non‐smokers were; 45.9% vs. 28.6%, 16.2% vs. 7.1%, and 35.1% vs. 7.1%, respectively. Among these, only the association between promoter methylation and tobacco smoking was statistically significant (P<0.05). Therefore, epigenetic aberration is considered to be a major causative event in p16 silencing by tobacco smoking. Loss of p16 protein expression was apparent in 49% (25/51) of the tumors, and was associated with tobacco smoking (P<0.05) and with histological type (P<0.05). These findings suggest that tobacco smoking leads to inactivation of the p16 gene mainly through the epigenetic mechanism, ultimately increasing the risk of NSCLC, especially the squamous cell histological type. |
format | Online Article Text |
id | pubmed-5926878 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2002 |
publisher | Blackwell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-59268782018-05-11 Frequent Epigenetic Silencing of the p16 Gene in Non‐small Cell Lung Cancers of Tobacco Smokers Yanagawa, Naoki Tamura, Gen Oizumi, Hiroyuki Takahashi, Nobumasa Shimazaki, Yasuhisa Motoyama, Teiichi Jpn J Cancer Res Article Epidemiological studies have demonstrated a causal link between tobacco smoking and lung cancer. We investigated the association between inactivation of the p16 gene and tobacco smoking in 51 non‐small cell lung cancers (NSCLCs). Aberrations of the p16 gene were studied by PCR single‐strand conformation polymorphism analysis, followed by direct sequencing, microsatellite analysis, methylation‐specific PCR, and immunohistochemistry. Mutations were detected in 3.9% (2/51) of the tumors; the tumors carrying mutations were from smokers. The incidences of loss of heterozygosity, homozygous deletion, and promoter methylation in 37 smokers vs. 14 non‐smokers were; 45.9% vs. 28.6%, 16.2% vs. 7.1%, and 35.1% vs. 7.1%, respectively. Among these, only the association between promoter methylation and tobacco smoking was statistically significant (P<0.05). Therefore, epigenetic aberration is considered to be a major causative event in p16 silencing by tobacco smoking. Loss of p16 protein expression was apparent in 49% (25/51) of the tumors, and was associated with tobacco smoking (P<0.05) and with histological type (P<0.05). These findings suggest that tobacco smoking leads to inactivation of the p16 gene mainly through the epigenetic mechanism, ultimately increasing the risk of NSCLC, especially the squamous cell histological type. Blackwell Publishing Ltd 2002-10 /pmc/articles/PMC5926878/ /pubmed/12417040 http://dx.doi.org/10.1111/j.1349-7006.2002.tb01212.x Text en |
spellingShingle | Article Yanagawa, Naoki Tamura, Gen Oizumi, Hiroyuki Takahashi, Nobumasa Shimazaki, Yasuhisa Motoyama, Teiichi Frequent Epigenetic Silencing of the p16 Gene in Non‐small Cell Lung Cancers of Tobacco Smokers |
title | Frequent Epigenetic Silencing of the p16 Gene in Non‐small Cell Lung Cancers of Tobacco Smokers |
title_full | Frequent Epigenetic Silencing of the p16 Gene in Non‐small Cell Lung Cancers of Tobacco Smokers |
title_fullStr | Frequent Epigenetic Silencing of the p16 Gene in Non‐small Cell Lung Cancers of Tobacco Smokers |
title_full_unstemmed | Frequent Epigenetic Silencing of the p16 Gene in Non‐small Cell Lung Cancers of Tobacco Smokers |
title_short | Frequent Epigenetic Silencing of the p16 Gene in Non‐small Cell Lung Cancers of Tobacco Smokers |
title_sort | frequent epigenetic silencing of the p16 gene in non‐small cell lung cancers of tobacco smokers |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5926878/ https://www.ncbi.nlm.nih.gov/pubmed/12417040 http://dx.doi.org/10.1111/j.1349-7006.2002.tb01212.x |
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