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Chemotherapy Toxicity Genes

Posted Oct 22 2008 6:18pm

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Imagine if you could predict who would get the nasty side effects of chemotherapy before giving it. We could then taper the chemotherapy giving less of a dose and achieve the same response. Well, the first part of that dream is here today. AtSt JudeChildren's Research Hospital they have been actively investigating pharmacogenomics and chemotherapy. In astudyto be released in the May 15th edition of Blood we have just that.

The majorfindingsinclude

  • During the induction phaseVitamin D Receptorpolymorphisms were linked with gastrointesinal symptoms (diarrhea, nausea, vomiting) 6.85 times more likely.
  • Polymorphisms in Cytochrome p450-Family 3-subfamily A-number 5, were almost 5 times more likely to have infections and Neurotoxicity
  • During consolidation phase the Reduce Folate Carrier polymorphism led to the GI side effects with a 10.4 odds ratio.
  • UGT1a1polymorphisms led tojaundiceas well as reduced clearance of an agent calledmethotrexate(a chemo drug) perhaps leading to increased toxicity as well

This is a major study, that has had some replication in one gene or another. But the compiling of these polymorphisms has not been done. Likely we will need one more round of evaluation. But after that...we could have a pharmacogenomic test for side effects.

The Gene Sherpa says: This is great, but how do we adjust the chemo to avoid these reactions. We will likely need an adjustment scale based on polymorphisms. AKA Personalized Medicine! I am certain St Jude's has this in the works. Let's keep our eyes peeled :)

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