Genetic Basis for Side Effect Susceptibility

Individuals metabolize chemotherapy drugs differently, and some may suffer severe – or fatal – side effects from the treatment. We identified a gene (GSTT1) that predicts whether children with leukemia will get severe side effects from chemotherapy. Children lacking GSTT1 have twice the likelihood of dying from complications from leukemia therapy as do children with GSTT1.

We are also investigating children’s susceptibility to dose-intensive chemotherapy. This type of treatment has led to more cancer cures, but it can damage blood cells and cause leukemia, even as it cures the original cancer. We are studying a nationwide group of children receiving some of the most dose-intensive chemotherapy, with the intent to identify biomarkers indicating patients’ risk of developing leukemia as a second malignancy. Eventually, this research could translate into new methods for catching second malignancies and reversing them in their early stages.

Long-Term Outcomes for Childhood Cancer Survivors

If children survive cancer, what does the future hold for their health? This is a vital question for the 250,000 cancer survivors under age 30 in the United States. Our laboratory is the biological repository for a cohort study, coordinated with the University of Minnesota [link to U of M appropriate site], of almost 15,000 childhood cancer survivors. We are using DNA collected from more than 10,000 cohort members to investigate genetic influences on the risk of cardiac side effects from treatment, as well as the risks of obesity in leukemia survivors and of second cancers in children treated with radiation therapy.