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Childhood cancer drugs cure now, may cause problems later, UB research shows
Date:12/16/2011

ne-related cardiomyopathy to a control group of 317 survivors without heart disease.

Using the candidate gene approach, Blanco and his team were able to identify a tiny gene variant related to the risk of cardiotoxicity.

"We pinpointed the genetic difference or polymorphism that makes an enzyme work faster or slower in patients," said Blanco, "slower is better."

They zeroed-in on carbonyl reductases (CBR1 and CBR3) -- two enzymes that break down anthracyclines into cardiotoxic alcohol metabolites. Blanco notes that in mouse models, higher levels of CBRs or faster enzymes dictate higher levels of these metabolites -- and more cardio toxicity.

The research showed that the risk of cardiomyopathy was significantly increased among individuals with two copies of the "G" version of the CBR3 polymorphism when exposed to low-to-moderate doses of anthracycline.

Blanco says that while the results of the study validated the findings of an earlier study in a totally independent cohort of cancer survivors, further study is required.

"We have to be careful," says Blanco. "So far, we are showing an association, not yet causation. Our next step will be to conduct a prospective study -- where we don't study individuals who were exposed to anthracyclines in the past but follow them in real time as they are receiving the drug and after."

What does this mean for children who are taking or have taken anthracyclines?

"If we stop using anthracyclines we will not be able to cure up to 90 percent of the children who suffer from acute lymphoblastic leukemia." Blanco says. "Parents must continue to have their children's health monitored long after the cancer is cured to identify cardiac problems if they develop."


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Contact: Sara Saldi
saldi@buffalo.edu
716-645-4593
University at Buffalo
Source:Eurekalert

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