Friday, January 29, 2010

The Assises de Génétique!

It's a fun little meeting, held every year in a different city, where French geneticists of all persuasions (meaning, I suppose, that cytogeneticists and somatic geneticists and epigeneticists are just as welcome as the usual one-gene-one-illness kind) gather to present and discuss the latest.

I haven't gone to all of them, but I did get to see Angers and Montpellier and now Stasbourg this way, and for a smallish meeting that covers a lot of scientific territory there's a lot of interesting science around.


This year one of the things in style is the deciphering of the genetic components of complex disorders. As a cancer researcher myself I was particularly interested in one of the talks in the opening plenary session, on the genetics of lung cancer.


(OMG that is one astounding onion soup! And an interesting beer to go with it.This is not a high-class restaurant I've chosen to dine and write in, with its plastic menu and paper placemats, but the first course is great. It's not your usual dark brown beefstock onion soup with a layer of bread and cheese on top, but something lighter with white wine, no cheese, and bread on the side.)

(Why am I dining alone? Well, I meant to meet up with friends at the Welcome Cocktail, but for some reason they planned that in a space meant for 300 people. After letting in 450, they started turning us away, and I wasn't among the lucky ones, having arrived independently just a bit late. Like 20 minutes after it started. How 'late' is that for a cocktail party?)


Getting back to science. Cancer is many things, and can be divvied up in many ways. One of the main ways is genetic vs environmental, with breast cancer being the poster child for hereditary risk (though less than 10 % of cases are strongly hereditary), and lung cancer sitting on the other end of the seesaw as the classic environmental disease (stop smoking! Now! All of you!). In fact, it has long been suspected that there are genetic factors that contribute to lung cancer. The effect of smoking is just so strong that they've been hard to identify.

Modern molecular biology to the rescue: Now that we can screen many thousands of markers in many thousands of people, gathering up 50,000 lung cancer cases and looking at markers across the entire genome is doable in a reasonable amount of time.

And they found stuff.


In Europeans, three loci (literally 'places in the genome', which usually correspond to genes, but don't always) are significantly associated with the risk of developing lung cancer. One of these was already known. Two are new, one at the tip of chromosome 5 and the other on chromosome 15. On chromosome 15 there's a cluster of genes around the marker that turned up hot, all of them components of the nicotine receptor in the brain. And it turns out that the hottest marker is a little change in one of these that makes it bind nicotine just a little bit better than the usual version.

Makes perfect darned sense!

People with this variant version experience greater dependence on nicotine than people without it. If they take up smoking, they're much less likely to be able to kick the habit. Doesn't mean they can't, but it's a significant handicap. Gives all the meaning to antismoking campaigns that lean on Don't Start.

So these people with the variant smoke more and for longer and expose themselves to more tobacco carcinogens. It's a gene that works _with_ the environmental factor. Not one or the other, but both together. (Just to be fair, having the variant does increase lung cancer risk for people who don't smoke, but its big clinical importance is in smokers.)

This only goes for Europeans. The variant is quite common in Europe (34 % of chromosomes there have it), but is not seen at all in Asians or Africans. Something else must be going on with them.


This is just the tip of the iceberg of gene-environment interactions. It's been several years now that the Nature vs Nurture arguement has been shown to be a false dichotomy in almost every domain. High-throughput gene screens on huge cohorts are beginning to give us the details.



Ronda Laveen said...

Absolutely fascinating! More, more, more!

And, I believe in Emily Post's guide, isn't 20 minutes late the recommended time for arrival?

Titus said...

Fascinating post, as Ronda says, more!

Oops. I'm a smoker.

Niamh B said...

That's harsh, about the cocktail party, but at least you got that lovely onion soup out of it... and that is very interesting about the nicotene gene, very interesting indeed! As Ronda says - more!

Bagman and Butler said...

Related, I suppose, to the hereditary/genetic factors for alcoholism. Some people have harder time quitting. But instead of cancer, we drive cars and kill other people. Still, like smoking, a disease. Just not one that wins friends and grant funding.

GingerV said...

interesting. so I have never smoked but lived 18 years with a parent that smoked, another 10 with a husband that smoked and maybe another 5 in a smoking workplace - smoking in the office being stopped in the mid 80s I think. Some of these time frames overlap meaning I am in a second hand smoking enviornment most of my day and night. I don't smoke but I dream that I do.... dream of drawing in smoke, the feel - the taste of it. My body addicted to nicotene? - we are many generation american but almost 100% european extract. (my father was 25% american indian and besides smoking until 50 yrs he drank with the expected outcome) So I have a strong predisposition to lung cancer? and My daughter who is american but 2nd generation dutch - has smoked since she was 15 - now 40 would not give it up for any amount of money - has an even stronger risk. Very interesting Dr NanU.
(word verf. Masta - using USA Southern accent - the masta of our life.)

NanU said...

There are certainly genes that contribute to the susceptibility to addictions of all sorts, Mark, though this one is specific for nicotine. The influence they have on getting hooked and staying that way are variable, and don't relieve the addict of all personal responsibility for their behavior. There are genes specific to alcoholism (involved in ethanol metabolism) or to various drugs, and even addictive behaviors in general (gambling, sex, shopping, eating, risk-taking, etc) where it's the compulsion to do something over and over that's the key, not the particular behavior.

Ginger - the hereditary risk is minimal and quite common. It's better at explaining why some people find it easier to quit. It would be interesting to see whether this one gene influences whether people surrounded by smokers are more or less likely to start themselves. At any rate, your environmental risk from breathing so much smoke through the years is probably the major risk factor here, regardless of your genes. The longer it's been since that environment stopped, the less likely you are to ever experience a negative consequence.
As for being addicted to nicotine, you need to be ingesting it somehow - dreaming doesn't count!

GingerV said...

I love your explanations, would have loved to have you as an university prof. even with no background in science I tend to get something out of what you say.... adding to my basic knowledge.
now back to recreating my computer data....