BLOG: April 2008
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
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
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
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 -
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
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