Effect of active smoking on the human bronchial epithelium transcriptome
<p>Abstract</p> <p>Background</p> <p>Lung cancer is the most common cause of cancer-related deaths. Tobacco smoke exposure is the strongest aetiological factor associated with lung cancer. In this study, using serial analysis of gene expression (SAGE), we comprehensivel...
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Format: | Article |
Language: | English |
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BMC
2007-08-01
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Series: | BMC Genomics |
Online Access: | http://www.biomedcentral.com/1471-2164/8/297 |
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author | Lam Wan L MacAulay Calum Ng Raymond T Lonergan Kim M Chari Raj Lam Stephen |
author_facet | Lam Wan L MacAulay Calum Ng Raymond T Lonergan Kim M Chari Raj Lam Stephen |
author_sort | Lam Wan L |
collection | DOAJ |
description | <p>Abstract</p> <p>Background</p> <p>Lung cancer is the most common cause of cancer-related deaths. Tobacco smoke exposure is the strongest aetiological factor associated with lung cancer. In this study, using serial analysis of gene expression (SAGE), we comprehensively examined the effect of active smoking by comparing the transcriptomes of clinical specimens obtained from current, former and never smokers, and identified genes showing both reversible and irreversible expression changes upon smoking cessation.</p> <p>Results</p> <p>Twenty-four SAGE profiles of the bronchial epithelium of eight current, twelve former and four never smokers were generated and analyzed. In total, 3,111,471 SAGE tags representing over 110 thousand potentially unique transcripts were generated, comprising the largest human SAGE study to date. We identified 1,733 constitutively expressed genes in current, former and never smoker transcriptomes. We have also identified both reversible and irreversible gene expression changes upon cessation of smoking; reversible changes were frequently associated with either xenobiotic metabolism, nucleotide metabolism or mucus secretion. Increased expression of <it>TFF3</it>, <it>CABYR</it>, and <it>ENTPD8 </it>were found to be reversible upon smoking cessation. Expression of <it>GSK3B</it>, which regulates <it>COX2 </it>expression, was irreversibly decreased. <it>MUC5AC </it>expression was only partially reversed. Validation of select genes was performed using quantitative RT-PCR on a secondary cohort of nine current smokers, seven former smokers and six never smokers.</p> <p>Conclusion</p> <p>Expression levels of some of the genes related to tobacco smoking return to levels similar to never smokers upon cessation of smoking, while expression of others appears to be permanently altered despite prolonged smoking cessation. These irreversible changes may account for the persistent lung cancer risk despite smoking cessation.</p> |
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institution | Directory Open Access Journal |
issn | 1471-2164 |
language | English |
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publishDate | 2007-08-01 |
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spelling | doaj.art-a559124091804d39813db61e7894492f2022-12-22T03:26:23ZengBMCBMC Genomics1471-21642007-08-018129710.1186/1471-2164-8-297Effect of active smoking on the human bronchial epithelium transcriptomeLam Wan LMacAulay CalumNg Raymond TLonergan Kim MChari RajLam Stephen<p>Abstract</p> <p>Background</p> <p>Lung cancer is the most common cause of cancer-related deaths. Tobacco smoke exposure is the strongest aetiological factor associated with lung cancer. In this study, using serial analysis of gene expression (SAGE), we comprehensively examined the effect of active smoking by comparing the transcriptomes of clinical specimens obtained from current, former and never smokers, and identified genes showing both reversible and irreversible expression changes upon smoking cessation.</p> <p>Results</p> <p>Twenty-four SAGE profiles of the bronchial epithelium of eight current, twelve former and four never smokers were generated and analyzed. In total, 3,111,471 SAGE tags representing over 110 thousand potentially unique transcripts were generated, comprising the largest human SAGE study to date. We identified 1,733 constitutively expressed genes in current, former and never smoker transcriptomes. We have also identified both reversible and irreversible gene expression changes upon cessation of smoking; reversible changes were frequently associated with either xenobiotic metabolism, nucleotide metabolism or mucus secretion. Increased expression of <it>TFF3</it>, <it>CABYR</it>, and <it>ENTPD8 </it>were found to be reversible upon smoking cessation. Expression of <it>GSK3B</it>, which regulates <it>COX2 </it>expression, was irreversibly decreased. <it>MUC5AC </it>expression was only partially reversed. Validation of select genes was performed using quantitative RT-PCR on a secondary cohort of nine current smokers, seven former smokers and six never smokers.</p> <p>Conclusion</p> <p>Expression levels of some of the genes related to tobacco smoking return to levels similar to never smokers upon cessation of smoking, while expression of others appears to be permanently altered despite prolonged smoking cessation. These irreversible changes may account for the persistent lung cancer risk despite smoking cessation.</p>http://www.biomedcentral.com/1471-2164/8/297 |
spellingShingle | Lam Wan L MacAulay Calum Ng Raymond T Lonergan Kim M Chari Raj Lam Stephen Effect of active smoking on the human bronchial epithelium transcriptome BMC Genomics |
title | Effect of active smoking on the human bronchial epithelium transcriptome |
title_full | Effect of active smoking on the human bronchial epithelium transcriptome |
title_fullStr | Effect of active smoking on the human bronchial epithelium transcriptome |
title_full_unstemmed | Effect of active smoking on the human bronchial epithelium transcriptome |
title_short | Effect of active smoking on the human bronchial epithelium transcriptome |
title_sort | effect of active smoking on the human bronchial epithelium transcriptome |
url | http://www.biomedcentral.com/1471-2164/8/297 |
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