GWASpirin! How GWASpirating!

There have been several studies of the beneficial effects of regular aspirin dose on diseases nobody thought aspirin had any relationship to.  This is not about pain, but about heart disease and, in recent years, even cancer.  A new study furthers this, by finding that people at risk of developing a collection of cancers, a trait called Lynch Syndrome after Henry Lynch, a very prominent expert in cancer at  Creighton University in Omaha, Nebraska.

Sufferers from this syndrome are vulnerable to form cancers in various tissues, including the large bowel.  It affects various tissues because at least in the major form of the syndrome, there is a mutation in a gene coding for a protein that protects DNA from being miscopied when replicated before cell division.  When the gene mis-fires, the DNA can accumulate mistakes.  In the billions of cells, some of them rapidly dividing in organs like the intestine, all it takes is one lineage of these cells to accumulate an unlucky set of genes mutated in this way (perhaps with risk variants that were inherited), to turn that cell into a tumor that can grow to become life-threatening.

Now, with all the GWAS in the world, it is ironic that the new findings--that replicated some earlier ones--find that it is good old fever-fighting ache-reducing aspirin that is responsible.  It is not clear why aspirin should have this effect, since aspirin in principle doesn't know which cell has got too many mutations in it.  The aspirin effect must be generic in relation to dividing cells, or to (say) inflammation in such tissues, to slow their growth or target them for destruction by the immune system.  Someone may know why this effect works, but we don't.

However, aspirin does seem to recognize cell components called platelets that accumulate around damaged cells.  When there are too many of these, aspirin helps clear things.  Of course, when clotting might be important, if you've been taking aspirin you may not form clots when you want to.  Perhaps cancers, which are masses that grow somewhat chaotically--but need blood supply and send out signals that stimulate blood vessel growth to 'feed' the tumor cells--may do this irregularly enough that aspirin somehow causes local hemorrhage or something of that sort, that starves or slows the tumor cells or tumor growth.  We're guessing, and doubtlessly some sources will have better explanations.  But one thing is that it was unexpected until a few years ago.

So, if whole genome studies are too often GWASpirating, here's a case in point:  A little GWAspirin, rather than multimillion dollar study, probably does much more preventive good than the amount of risk associated with by far most of the genes identified by GWAS to date.

Now, interestingly, genomewide association studies are done because one has insufficient knowledge of the cause of some disease or normal trait, so we simply search the whole genome to find those genes that at least contribute.  Large studies have typically found few statistically significant effects, and those that are found usually have made only very small individual contributions to risk.  That's why many feel that by now we know the story and GWAS have little future potential to generate GWhiz! findings, and the funds should be spent in more genetically focused ways.

In this case, however, hypothesis-based or focused genetic science probably would not have found the aspirin effect.  That is the serendipity side of science, and we're all fortunate that it works from time to time.

Whether the aspirin effect turns out to be as it seems, or fades for some reason upon further knowledge, only time will tell.  There are cons as well as pros: the effect is small, if any, on those not already at high risk of these cancers, and aspirin is a risk factor for ulcer and stroke, or even perhaps excessive bleeding in accidents and injuries.  So the balance needs to be evaluated and it will be difficult for any neutral party to identify it.  But at least here, rather than a zillion-dollar study, the cheapest of medicines goes far further.  What a headache for those dedicated to GWAS!