生物谷報道：發(fā)表在8月29日的在線刊物《英國醫(yī)學研究理事會基因組學》（BMC Genomics）上的文章表示吸煙可能永久性的打開某些基因,，這將幫助解釋為何有吸煙史的人相比那些從未吸過煙的人患肺癌的幾率更高,。
由BC癌癥機構(gòu)的Wan L Lam和Stephen Lam領(lǐng)導的加拿大研究小組分析了24份現(xiàn)在正在吸煙、有過吸煙史及從未吸煙的人的肺部樣本,。小組利用一種被稱為基因表達序列分析（SAGE）的技術(shù)得到了樣本數(shù)據(jù)庫,，這可以幫助確認基因活動的模式,。
在任何時候,，細胞中都只有約1/5的基因被打開，但環(huán)境變化——例如吸煙——將導致基因活性改變,。其中有些改變不可逆,，有些可通過停止吸煙被逆轉(zhuǎn)?？赡婊蛞话愫彤惿镔|(zhì)功能（管理不由身體產(chǎn)生的化學物質(zhì)）,、核苷代謝、黏液分泌有關(guān),。而吸煙將不可逆的破壞一些DNA修復基因,，并關(guān)閉一些對抗肺癌的基因。
科學家還確認了一些曾被認為和吸煙無關(guān)的基因,，它們在吸煙者中被打開,。其中之一是CABYR，它和精子游動及腦癌相關(guān),。
小組進一步研究了和其它功能相關(guān)的基因變化,，結(jié)果可以將找到的基因分為3類：停止吸煙后可逆（和黏液結(jié)構(gòu)成分有關(guān)的TFF3、CABYR等）,；部分可逆（黏液素基因MUC5AC）,；不可逆（調(diào)控COX2的GSK3B基因等）。以上結(jié)果在針對另一組對象分析后得到了確認,。
文章第一作者Raj Chari說：“那些在停止吸煙后仍無法恢復正常的基因和功能或許可以解釋為何有吸煙史的人相比從未吸煙的人患肺癌的幾率還是要高,。”這是目前為止最大規(guī)模的SAGE研究。
吸煙是造成85%肺癌的原因,，而有吸煙史的人占新診斷病例的一半,。 （援引教育部科技發(fā)展中心）
英文原文鏈接：http://www.physorg.com/news107610787.html
原始出處:
Effect of active smoking on the human bronchial epithelium transcriptome
Raj Chari , Kim M Lonergan , Raymond T Ng , Calum MacAulay , Wan L Lam and Stephen Lam
BMC Genomics 2007, 8:297 doi:10.1186/1471-2164-8-297
Published 29 August 2007
Abstract (provisional)
Background
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.
Results
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 TFF3, CABYR, and ENTPD8 were found to be reversible upon smoking cessation. Expression of GSK3B, which regulates COX2 expression, was irreversibly decreased. MUC5AC 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.
Conclusions
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.
