生物谷报道：发表在8月29日的在线刊物《英国医学研究理事会基因组学》（BMC Genomics）上的文章表示吸烟可能永久性的打开某些基因，这将帮助解释为何有吸烟史的人相比那些从未吸过烟的人患肺癌的几率更高。
由BC癌症机构的Wan L Lam和Stephen Lam领导的加拿大研究小组分析了24份现在正在吸烟、有过吸烟史及从未吸烟的人的肺部样本。小组利用一种被称为基因表达序列分析（SAGE）的技术得到了样本数据库，这可以帮助确认基因活动的模式。
在任何时候，细胞中都只有约1/5的基因被打开，但环境变化——例如吸烟——将导致基因活性改变。其中有些改变不可逆，有些可通过停止吸烟被逆转。可逆基因一般和异生物质功能（管理不由身体产生的化学物质）、核苷代谢、黏液分泌有关。而吸烟将不可逆的破坏一些DNA修复基因，并关闭一些对抗肺癌的基因。
科学家还确认了一些曾被认为和吸烟无关的基因，它们在吸烟者中被打开。其中之一是CABYR，它和精子游动及脑癌相关。
小组进一步研究了和其它功能相关的基因变化，结果可以将找到的基因分为3类：停止吸烟后可逆（和黏液结构成分有关的TFF3、CABYR等）；部分可逆（黏液素基因MUC5AC）；不可逆（调控COX2的GSK3B基因等）。以上结果在针对另一组对象分析后得到了确认。
文章第一作者Raj Chari说：“那些在停止吸烟后仍无法恢复正常的基因和功能或许可以解释为何有吸烟史的人相比从未吸烟的人患肺癌的几率还是要高。”这是目前为止最大规模的SAGE研究。
吸烟是造成85%肺癌的原因，而有吸烟史的人占新诊断病例的一半。 （援引教育部科技发展中心）
英文原文链接：http://www.physorg.com/news107610787.html
原始出处:
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.
