Wednesday, August 17, 2016

Smoking: could genetic testing help smokers' cause?

Genetic research holds out the hope that health advice and public policy could be targeted more precisely. The risks of smoking are not "one size fits all."

"Family, twin, and adoption studies also convincingly demonstrate a substantial genetic contribution to the development of addiction to nicotine, alcohol, and illicit drugs. Heritability estimates for nicotine, alcohol, and drug addiction are in the range of 50% to 60%." (1)

If this is so, then theoretically people could be genetically tested for their vulnerability to substance addiction and advised accordingly. And the others could continue in their habit, moderately reassured that they could stop if they so chose. 

Testing might also help with more precise information about health risks. A longitudinal study of male British doctors (2) suggests that the average reduction in life expectancy is 10 years, but "that is not to say that all such smokers died about 10 years earlier than they would otherwise have done: some were not killed by their habit, but about half were, thereby losing on average more than 10 years of non-smoker life expectancy. Indeed, some of those killed by tobacco must have lost a few decades of life." It may be possible to identify the ones who are most at risk of dying in their middle years.

The same study also suggests that smoking for a few years may not be significantly life-threatening. For those in the 25-34 age group - where smoking prevalence is highest (3) - if they give up during this time, their life expectancy is almost exactly the same as for never-smokers:

"Mortality in relation to smoking", etc. - Fig. 4 (selected area)

If potential smokers could be forewarned of their likelihood of developing an addiction, and of their chances of dying very early from diseases associated with the habit, then the life expectancy gap might be narrowed without blanket bans. 

Those who went ahead despite personalised warnings would at least be doing so on the basis of better information - and that then becomes a liberty issue, like hang-gliding (and cycling, the most dangerous form of transport).*

(1) "Genetic Vulnerability and Susceptibility to Substance Dependence" L.J. Bierut, US National Library of Medicine National Institutes of Health, February 2012 -
(2) "Mortality in relation to smoking: 50 years' observations on male British doctors" Doll, Peto & Boreham, BMJ, May 2004 -
(3) ASH "Facts at a glance", June 2016 -

*I was wrong, I'm afraid. Motorcycling is worse: 1,789 KSI (killed or seriously injured) per billion vehicle miles vs. 1,036 for pedal cycles. 
I'm disappointed - I wanted something to get back at the Puritans of the road.


James Higham said...

How about the govt. just getting out of micromanaging people's lives?

Sackerson said...

I duck my head while suggesting that addiction is a challenge to the concept of liberty.

James Higham said...

Yes but there is addiction and addiction. We're all addicted to something.

A K Haart said...

Perhaps an addiction to conspicuous cycling is reflected in our DNA, in which case parents could be given personalised warnings for their children.

Flaxen Saxon said...

Ooop, apologies for commenting on the wrong post. That's what you get for commenting in a hurry. I would ask our gracious host to delete my previous ramblings and place his reply here otherwise my reply will make no sense. Next time I will endeavour to make more time so I get the job done properly.

Regardless of the hectoring moralistic stance of the article quoted, I would like to make a few comments re the science as this something I know something about as I work as a professional geneticist. I'm involved in analysing genetic profiles and I can tell you that correlating genetic change with physical clinical ailments can be challenging. Now when you come to complex behaviours such as addiction, correlation is almost impossible. First off there are problems defining what 'addictive' behaviour' actually is. Experts in the field often can't agree. When I say genetics is complex I'm being a master of understatement. Behaviour is undoubtedly under the control of genetics however, even relatively 'simple' well defined behaviours are under the control of many genes which not only interact with themselves but with the environment, which is of course a highly complex variable. O so clever geneticists can produce screeds of genetic data from an individual but if we are honest we don't have a clue of what most of it means. As I've said elsewhere: The devil is in the interpretation. Currently you can read what you like in a person's genome and come up with whatever the fuck you like.

Flaxen Saxon said...

This comment is in reply to the comment made by our host to my above comment which I initially placed elsewhere. Sorry for the confusion. I'm a mad old sod.

Identical twin studies have always been held as the 'Gold Standard' in genetic research. The idea being of course that they are genetically identical- which of course they. However, it doesn't mean they have identical gene expression profiles. The phenomenon of epigenetics is about environmental influences, often micro-environmental changes affecting gene expression. Even during pregnancy identical twins will be differentially influenced by the micro-environment of the womb resulting in differences in gene expression between the twins. An old fashioned geneticist such as myself was weaned on the 'central dogma paradigm' which stated that information can only flow from DNA to RNA to proteins and that the environment could not effect genetic change. Epigenetic changes don't alter gene expression by altering base pairs or influencing gene promoter elements. They change the structure of the DNA by methylation or other conformational changes which turns genes 'on' or 'off'. Research has shown that these changes are inherited and can become permanent through the generations and that the environment, mostly during pregnancy, is a potent means for altering gene expression. This of course adds another layer of complexity when we examine genetic profiles from individuals thus making deductions even harder. Also we can't detect these changes by simple base pair sequencing of genes but we have to use other tools such as looking for the elements (RNA) of gene expression itself or looking for hypo or hypermethylated sites, etc.

As for predicting who is likely or less likely to succumb to the common diseases in our middle years: Apart from diseases following a single gene model, predicting from a patient's genetic profile is very hard. Interesting you can get your genetic profile analysed these days by companies who will take your gelt and give you a biological susceptibility profile. When folk have sent their DNA to different companies they often receive different profiles even though the raw data is the same. It is incredibly difficult to extrapolate from this data due the complexity of genetic interaction. Perhaps we will be able to do it one day, but not yet. And I haven't touched on the ethical. social and practical ramifications of such testing, which are legion.

I'm not involved in the recreation thingy although I do have an active interest in old weaponry, armour and military history, sad old git that I am. Sorry if I haven't addressed all your comments but I think I've rambled on enough and your readers will start to lose the will to live.........

Sackerson said...

In response to Flaxen Saxon’s first comments above (which originally appeared by accident on a different post):

1. The first link says the estimate is based on studies of twins, I don't know if that makes it any better, though even if true I'd have to take your point that even if there is a correlation working out the causation is a devil of a job.

2. However, is it any easier to determine likelihood of falling victim to those deadly middle-year diseases?

3. I think if smokers want to push back at the blanket ban the best way is to go for targeted derogations at first - win at least one battle on ground of your choosing, before you turn the tide of the war. The El Alamein approach.

4. Some (e.g. Peter Hitchens) are inclined to doubt that there is such a thing as addiction, though I'm not so sure. If it does exist and some are more prone to it, does that bear on the concept of liberty at least to the extent that people need more information to make their personal decision?

5. Looking at your blogging avatar, are you into the re-creation thing? Went to a little open-air exhibition by Brumvik people in Birmingham last weekend. Interesting.

Sackerson said...

In response to Flaxen Saxon's second comment:

Fascinating! Thank you so much for your expert comment!

This opens up a can of worms. For example, about the importance of prenatal conditions - actually that could go further, an outstanding medic friend told me that ideally both partners would have to be in best fitness and nourishment before conception.

Other implications include: the potential predictive capacity of genetic testing was exercising the life insurance industry years ago.

And then there's selective abortion based on gender and other preferences. Lord Byron, with his club foot, might never have been born (and there is a tradition that says Jesus of Nazareth limped).

Sackerson said...

@ A K Haart: I'm a little grumpy at some cyclists' behaviour, here and in Vienna. I may do a have-a-go piece some time.