Genetic variation sets stage for second cancer after childhood Hodgkin

Two small genetic variations can predict which patients with Hodgkin lymphoma are most likely to develop radiation-induced second cancers years after treatment, revealed a recent study.

More than 90% of patients with Hodgkin lymphoma survive the disease after undergoing radiation and chemotherapy, but nearly 20% of those treated as children develop a second cancer within 30 years, according to a statement issued by the University of Chicago (Illinois) Medical Center, where senior study author Kenan Onel, MD, PhD, is an associate professor of pediatrics and a member of the university's cancer biology committee.

Onel and associates analyzed the genomes of 178 patients with Hodgkin lymphoma who had received radiation and chemotherapy when they were 8 to 20 years old. A total of 96 developed second cancers over the ensuing 30 years. When the investigators scanned each patient's genome, they found three variations in tiny genetic variations known as single nucleotide polymorphisms that appeared far more often in the persons with second cancers.

Two of the three markers remained significant in a second set of patients, 62 of whom developed a second cancer and 71 of whom did not. Those two markers are positioned near the PRDM1 gene, and appeared to decrease activation of the gene but had no detectable effect on any other genes. Cells with the protective version of both markers expressed PRDM1 after being exposed to radiation. Cells with the variants linked to subsequent cancers did not produce any PRDM1.

“These data suggest a new gene-exposure interaction that may implicate PRDM1 in the etiology of radiation therapy-induced [second malignant neoplasms],” wrote the researchers in their online report for Nature Medicine.

In the University of Chicago statement, Onel observed that this finding will enable more effective identification of children who are most susceptible to radiation-induced cancers before treatment begins, and allow clinicians to modify their care to prevent this complication.
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