Saturday, December 17, 2011

DNA death predictors: What do they really tell you?

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Genetic tests lay odds on killer diseases, and now a "health check" for your chromosomes spots traits that could reveal your lifespan ? if it really works

MY PATERNAL grandfather lived until he was 89; his brother outdid him by a decade. My grandmothers made it to 85 and 93. My parents are both alive and kicking at 73 and 82. The only people to die young in my family were killed in wars or industrial accidents. Maybe I am just clinging to the rosy bits, but this is the information I choose to employ when predicting my own longevity. I reckon the odds are with me, and I'm not interested in knowing if I'm wrong. My greatest fear about the timing of my death is that it will come many decades after I have exhausted my supply of money.

It seems I am unusual, however. Apparently many people are thirsting for a little extra information to help them calculate how long they have left. How else can you explain the burgeoning number of commercial enterprises promising to meet that desire? Already, gene-sequencing companies such as 23andme, deCodeMe and Navigenics can do a quick scan of your risk of developing everything from lung cancer to multiple sclerosis. Now two new firms are offering to tell us how well we are ageing, based on an analysis of structures at the ends of our chromosomes called telomeres.

If these developments continue, a person's lifespan could become as quantifiable as the shelf life of a carton of milk. So instead of parading around blissfully unaware of how long we have left, we could find out our own use-by dates. For some, this knowledge would be a burden, while others may be glad of the chance to plan their future. But whether you find the prospect of being able to foretell your own death terrifying or enticing, how realistic is it? Are these new tests really a game changer? After all, we have long been able to test for life-threatening factors such as high cholesterol and blood pressure. And while a better understanding of the biology of ageing is bound to tell us even more, surely the date of one's death will always remain the great unknowable?

This brave new age of scientific soothsaying began a few years ago with the invention of home genetics tests that promise to alert you to things that might contribute to your ultimate decline. It couldn't be simpler. You order the kit online, receive it through the post, collect a cheek-swab sample of DNA while sitting on your own couch and then mail it off for analysis. The news comes back by email a few weeks later. In the interests of science I gave it a go.

You decide

I soon discovered a fundamental problem: the results are wide open to interpretation, making it easy to reconcile them with the views you already hold. Say you learn that, like me, you are one of those unlucky people whose risk of a heart attack goes up 60 per cent just by drinking a third cup of coffee every day. Bad though that sounds, the chances you will have a coffee-induced heart attack are still very low - and that it will kill you, lower still. Besides, if you scratch around enough, you can probably find something to offset even that small risk - such as your slightly lower-than-average odds of heart attack in general. That's what I did. And I concluded that my grandparents might still be my best guide to my longevity.

To cut a long story short: except for finding out whether you are susceptible to a few single-gene killer diseases, an inventory of genes is not very informative for anyone wanting to know how long they have got. A big list of small risks simply is not going to tell you what your odds are of making it to 95, or even 60. Will something called gastric cardia adenocarcinoma be what takes me out - my risk of getting it is 0.08 per cent, compared with an average of 0.07 per cent? Or will it be the more common melanoma, which I am ignoring because my risk is 1.3 per cent, compared with an average of 0.7 per cent?

According to Timothy Caulfield, a bioethicist and lawyer at the University of Alberta in Edmonton, Canada, who has been looking into how people react to tests like these, my attitude isn't uncommon. "People don't seem to do much with this risk information," he says. "They don't freak out. And they don't start exercising more, eating better or getting more screening." This should not surprise us, he adds, since we have never responded much to other more traditional predictive information, such as weight, blood pressure and cholesterol levels.

In fact, our ostrich-like attitude to genetic warning signs may even be quite sensible. Eline Slagboom at the Leiden University Medical Center in the Netherlands and her colleagues found that healthy people in their 80s and 90s were no less likely than the rest of us to carry gene variants, or alleles, known to increase the risks of heart disease, cancer and type 2 diabetes (Proceedings of the National Academy of Sciences, vol 107, p 18046). "These people from long-lived families have exactly the same numbers of deleterious alleles," she says. The difference, however, is that they probably possess other genes that keep the dangerous ones at bay. Although none of these have been identified so far, Slagboom and colleagues have discovered four separate areas of the genome that seem to be important. They suspect the critical genes will be unglamorous, controlling aspects of metabolism, inflammation and immunity.

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