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“My old addictionChanged the wiring in my brainSo that when it turns the switchesThen I am not the same…”-David Wilcox – “My Old Addiction”I quit smoking in January of this year, shortly after we found out Dr O’C was pregnant. The idea of smoking around my child was the straw that knocked the monkey of my back (if you’ll pardon the mixed metaphors). Now I, like virtually everyone else in the world, knew that smoking is an ultimately lethal habit. I knew exactly how much it cost, that it was rapidly becoming socially unacceptable and that it made me stink and my teeth brown, but I’ve never been able to quit for more than a few months until this time around. And I’m very grateful that I’ve finally been able to quit because you don’t often see any good news coming out of the scientific community regarding the health benefits of smoking.One thing that I didn’t know, or that I hadn’t acknowledged, was that not all the damage that’s done by two decades of smoking is fixable. When one goes to the doctor and gets the lecture about stopping it generally includes only the benefits of quitting – after 24 hours your blood oxygen levels are back to normal, after a year your risk of heart disease is reduced by one half and so on. What the doctor generally doesn’t say is that a former smoker is always going to be at greater risk of developing lung cancer.Forthcoming work by researchers at the British Columbia Cancer Research Center in the journal BMC Genomics focuses on the reasons for this phenomena. This group looks at the effects of cigarette smoking on gene expression in the lungs. This isn’t surprising as smoking a cigarette is pretty much inhaling a little cocktail of toxins. What is a little bit more surprising is that some genes’ expression is irreversibly changed in smokers.First, a little background on gene expression. A gene is expressed when its DNA is transcribed into RNA and ultimately into a functional protein or enzyme, in other words gene expression refers to a gene being “turned on”. Virtually every cell in the human body has the same DNA, thus the same genes. There is no difference in the DNA or genes of a brain cell and a skin cell. What allows these cells to differentiate is the decision as to which genes are turned on at any given time. [tag]Gene expression[/tag] can be measured in very specific and quantitative ways and in a tissue specific manner.In this paper Chari and his colleagues try to measure the differences in gene expression in the lining of the respiratory tract of smokers, non-smokers and former smokers. This tissue, known as the bronchial epithelium, is the most exposed to cigarette smoke and often where lung cancers are initiated. This is not the first time this type of work has been done, but the researchers use a more robust means of measuring gene expression and a second type of measurement to confirm some of the important results. Past research has shown that there are a number of genes that are differentially expressed in smokers relative to non-smokers. This work is trying to identify additional genes with differential expression and to establish whether expression of those genes goes back to normal when one quits smoking. Genes are termed either reversible or irreversible in terms of their expression. Genes with reversible expression are similar in their expression levels in non-smokers and former smokers but different in current smokers. Irreversible genes would be similar in expression levels in current and former smokers but different in non-smokers.Good news first – about half of the genes that the group identified were expressed at a different rate in current smokers than former and non-smokers – thus reversible. Many of these were involved with mucus secretion in the airways, in smokers production of protective mucus is increased to cope with the irritants in cigarette smoke. Over time after quitting this is no longer necessary and the expression of these genes is reduced. Interestingly, a gene which is highly expressed in some brain tumors is also one whose expression is reversible when smokers quit.However, not all the news is good for former smokers. The other half of the genes that were differentially expressed between smokers and non-smokers were not reversible. In other words, even a year after quitting these genes are expressed at the same level as a current smoker. Most notable among these genes are some that are involved in DNA repair. When DNA is damaged or mistakes are made in its copying there are specific enzyme complexes that are responsible in fixing these lesions. When repairs are not made, mutations can occur. Mutations in some genes can result in cancer. Thus, irreversible changes in gene expression of some of these genes may be responsible for the increased risk of lung cancer even in former smokers.The take home message here is that smoking has long-term, potentially permanent, effects on expression of genes in the lungs. Some of these changes are likely to be responsible for the increased rate in lung cancer in ex-smokers compared to non-smokers. There are a few problems with this research. The group isn’t able to look at the effect of time – how long one has been a smoker and how long it’s been since they stopped. Does the expression of these genes ever go back to normal? The primary technique they use to measure gene expression (SAGE, for those in the know) is a little bit error prone. But these problems do not affect their general conclusions. What’s less clear, and not addressed in this study, is why? Are certain genes more susceptible to smoking induced mutation or is their something beyond genetics (epigenetic) responsible? There’s certainly room for more work.A final note – part of me after I read this wanted to say “Screw it, I may as well smoke!” But the thing that is important to remember is that most of the genes return to their normal levels after a year off of the cigarettes. The advantages if not smoking – financial, social and medical – far outweigh any bitterness I might have about something that all smokers must know at some level, once you start you are irrevocably changed.Image CreditsCigaretteSilhouetted smoker