Tp53 gene variation, cancer, race, and stroke recovery

There is a gene, with the exciting name of Tp53, that, among other things, regulates apostosis (programmed cell death). Apostosis is actually good for a number of reasons, but one thing that it does is get rid of damaged cells before they cause problems. There are, however, two variants of this gene: one has the amino acid arganine, in which apostosis proceeds normally, and the other, which has the amino acid proline, where apostosis is curtailed. The arganine variant has been shown to protect individuals from the development and spread of cancer cells. This is a good thing, of course. However, apostosis of brain cells occurs in the aftermath of a stroke, and if it is not checked, this can delay or prevent an individual’s recovery. You can imagine, then, that a new study finds that people with the arginine variant do not recover as well from strokes as those with the proline variant. From a summary in ScienceNews:

Of people who had a poor prognosis after a stroke, about 81 percent carried two copies of the arginine variant. About 91.5 percent of people with a poor outcome after a hemorrhage had the arginine variant. None of the people with two copies of the proline variant had bad outcomes after either stroke or hemorrhage. People with one copy of each variant tended to have good prognosis after either type of brain injury.

One commentator suggests that his may not apply equally well across racial groups. Again, from the summary:

“We know already that there’s no way this is going to hold up in African Americans,” says Maureen Murphy, a cancer biologist at the Fox Chase Cancer Center in Philadelphia. African Americans tend to have the proline version of p53, but also have high rates of stroke, often with very poor outcomes, she says. It will be important to repeat the study in other ethnic groups to determine the variants are good predictors of stroke outcome for everyone.

References

Gomez-Sanchez, J.C., et al. (2011). The human Tp53 Arg72Pro polymorphism explains different functional prognosis in stroke. Journal of Experimental Medicine. 209: online.

The personal genome project, genetic privacy, and personal medicine

Last month, Diane Rehm of NPR had an interesting dicussion on DNA sequencing and personal genomics (you can listen to the 51-minute show in its entirety here). The completion of the human genome project in 2003 held the promise of using an individual’s genetic information to optimize their treatment. One example that the show uses is that of Google co-founder Sergey Brin, who has discovered that he possesses a mutation in his LRRK2 gene that may increase the likelihood of him developing Parkinson’s disease later in life. Nevertheless, the program’s guests demonstrate that there are still significant hurdles to truly effective genetic-based “personalized medicine.” A couple of interesting points from the show:

1. The cost of genome sequencing has declined greatly over the past decade or so. Some companies, like 23andMe (which was founded by Brin’s wife Anne Wojcicki) will sequence parts of your genome for about $500. For those of you interested in getting your entire genome (all 3 billion base pairs) sequenced, you can, with the consent of your doctor, send samples to companies like Illumina for the bargain price of about $20,000 (if you think that’s a bit pricey, consider that a decade ago it would have cost you about $1,000,000).

2. One of the guests, Dr. Arthur Caplan, provides examples of how people can react to genetic information. The most striking is the case where a father wanted to have his 13-year-old daughter tested for mutations associated with breast cancer risk (the family had a history of the disease). The father stated that if his daughter tested positive for one or more of the mutations, he would have her breast buds surgically removed to make sure that she did not suffer the same fate as other family members (Dr. Caplan does not tell us what ultimately happened with this case). One of the points that Dr. Caplan makes with this and other examples is that, although genetic screening can provide useful information, external environmental factors interact with genes in very complex ways, which currently makes it very difficult to assess an individual’s chances of developing conditions like cancer based simply on the presence or absence of particular genetic mutations (but see Personalized medicine in 10 years?).

3. All three of the guests discuss the issues surrounding genetic privacy. Once you submit samples for genetic sequencing, how can you be sure that your information will be kept private? If it is not kept private, what can it be used for? The importance of this issue is revealed by the signing of the Genetic Information Non-discrimination Act (GINA) by president Bush in 2008, which prevents discrimination based on genetic information when it comes to insurance and/or employment.  

Check out the show and hit us up with your comments: Would you want your genome to be publicly available? Would you even want to know what your genome looked like? If you had the information, what would you do with it?

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