Two genetic variations can help predict which survivors of Hodgkin's lymphoma are most likely to develop radiation-induced second cancers years after treatment, according to a genome-wide association study published online July 24 in Nature Medicine.
A U.S. and Canadian multi-institutional study analyzed the genomes of 178 Hodgkin's patients who had been treated between the ages of 8 and 20 with chemotherapy and radiation therapy. The researchers found a significant correlation with the presence of two markers located near a gene known as PRDM1 in the 96 patients who had developed second cancers within 30 years.
More than 90% of patients treated for Hodgkin's lymphoma survive, but nearly 20% of those who receive treatment as children develop a second cancer within 30 years. This cancer risk, which is the second leading cause of death for long-term survivors of Hodgkin's lymphoma, increases with the level of radiation dose exposure and the age at time of treatment, with younger age increasing susceptibility.
Researchers focused on 665,313 single nucleotide polymorphisms, or genetic variations, when they scanned each patient's genome. They found three variations that appeared far more often in patients with second cancers. When the study was repeated with another cohort of 133 patients, of whom 46% had developed a second cancer, two of the three genetic markers were significant (Nature Medicine, July 24, 2011).
The markers were positioned near PRDM1, in a small region known as 21q on chromosome 6. They appeared to decrease activation of the PRMD1 gene, but had no detectable effect on any other genes, according to senior author Dr. Kenan Onel, PhD, associate professor of pediatrics at the University of Chicago, and colleagues. Cells with the protective version of both markers expressed PRDM1 after being exposed to radiation.
Knowing in advance who is at risk could help physicians tailor treatment for those who are more susceptible to radiation-induced cancers, according to the authors.
"This finding means that we can better identify children who are most susceptible to radiation-induced cancers before treatment begins and modify their care," said Onel. "Luckily, our options for Hodgkin's are broad enough that we can find ways to control the initial disease without relying on radiation therapy."
