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BLOG: April 2008

Smoking genes

Most everyone knows that smoking forms addiction. But it is not equally addictive for all, and the bio-mechanism through which it actually makes you addicted depends on - what else - your genes. It is your genome that also decide how vulnerable you are to developing lung cancer as a result. Scientist are beginning to tackle the question: just how your genes determine your body's response to nicotine. Three recently published independent studies on this subject have come to some common points on one, and some contradictions on the other hand.

The largest study, led by Kari Stefansson from deCode Genetics of Iceland (published in Nature), on nearly 14,000 Iceland smokers, has concluded that variation in a single nucleotide (pair of nucleic acids bridging over the DNA strands) in a gene on the long arm of chromosome 15 strongly correlates with being a heavy smoker. This variation can be passed to you by either mother or father (since we get two sets of genes, one from each parent), or both.

It is estimated that about 40% of population has such variation in one set of genes - either that inherited from father, or from mother - and about 10% have it in both sets of genes.

According to the study, this particular gene variation increases smoker's risk of developing lung cancer by 30%. So those that inherited the variation from both parents have the risk higher by 70%. The increased risk is seen as directly related to the rate of smoking, which in turn strongly depends on how smoking affects your brain chemistry - specifically, the intensity and type of response of your nicotinic receptors, which is controlled by this gene.

The other two studies - one led by Dr. Paul Brennan from the International Agency for Research on Cancer, France (11,000 participants), and the other by Dr. Christopher Amos for M.D. Anderson Cancer Center in Houston (3,000 lung cancer patients, former smokers), both published in the Nature Genetics journal, have also found that this particular genetic variation plays significant role in lung cancer development. Their risk increase figures are also nearly identical to those in Stefansson's study. However, they don't see the increased cancer risk being the consequence of the rate, or duration, of smoking; rather, that

the genetic variation itself
amplifies carcinogenic effect of smoking.

This is implicated by the results of Brennan's study, which included several hundreds non-smokers, who also showed an elevated lung cancer risk if affected by this genetic variation.

Both, Brennan and Amos also point out that another SNP (single nucleotide polymorphism) in this particular gene could be of significance, as well as two other nicotinic-receptor-controlling genes present in that sequence of the chromosome 15.

Obviously, more research needs to be done to determine with certainty how exactly genes influence one's response to nicotine. The general effect of nicotine on the nicotinic receptor is that it stimulates release of dopamine, a "happy hormone". But the extent of this, as well as its effect can very significantly from one person to another.

To some folks smoking just doesn't do it. For others, it merely adds some sort of "extra" to their already positive overall mental state. But for some it makes the difference between feeling down and depressed, and not. In other words, nicotine here acts as anti-depressant, unfortunately with all the bad adverse side-effects. It is the last group of people that will find it most difficult to quit.

This implies that factors determining smoking addiction go beyond nicotinic receptors alone, to for whatever reason

unbalanced neurotransmitter chemistry.

One of the possible causes for it could be anything that disrupts flow of nutrients needed for neurotransmitter production and metabolizing. For instance, prolonged stress can drain you of detox nutrients needed to metabolize (break down) stress hormones - more likely if you were low on these nutrients to begin with - so you become constantly stressed. This will likely suppress your happy hormones, and make you feel down and depressed. Then, if you lit a cigarette, it can cause more dopamine being injected into your system, making you feel relieved, more at ease.

Of course, there are other factors possibly involved in development of smoking addiction. From making teenager feeling more mature and independent, to experiencing calming relief from touching and manipulating familiar object, or from repeating what amounts to a ritual - psychological factor is often significant.

Thus it is both, "smoking genes" and "all that's in your head", determining how addicted - or not - you'll become to smoking, once you give it a try. While there is not a single good reason to start smoking, if you already have, it is good to know what is it that could make it very difficult for you to quit.