Radiation treatment for one type of cancer can, unfortunately, raise the lifetime risk of developing a second malignancy somewhere else in the body. But doctors have until now had a tough time forecasting who is at the most risk of these secondary cancers.
Now, researchers have identified two genetic variations that can predict which people treated for Hodgkin’s lymphoma are most likely to develop other tumors decades later in life.
“They used very wise scientific intuition and they got some place very interesting,” says Stephen Channock, head of translational genomics at the US National Cancer Institute in Bethesda, Maryland, who was not involved in the study. “It’s a very exciting scientific finding.”
A team led by University of Chicago pediatrician Kenan Onel recruited around 200 people diagnosed with Hodgkin’s lymphoma as children, half of whom developed second cancers in adulthood. Reporting online in Nature Medicine yesterday, the researchers performed a genome-wide association study (GWAS) and discovered three single nucleotide changes that were far more prevalent in people with second cancers.
“They did a GWAS in a very small study — 100 cases and 100 controls — but the effect they saw was very strong,” says Channock. The study authors then repeated the analysis using a different set of cancer patients, and found that two of the three DNA markers remained significant. Specifically, people with either one of these two gene variants were two- to four-times more likely to develop second cancers.
Both of the DNA markers sit on chromosome 21 near a gene called PRDM1, which encodes a protein involved in the maturation of B cells — key immune cells that go awry in lymphoma. “Taken together,” the authors write, “our findings support a previously unknown role for PRDM1 as a radiation-responsive tumor suppressor.”
If the results are validated in larger cohorts, the authors suggest that physicians could screen for the markers and then tailor therapies accordingly to avoid giving radiation to those most susceptible to second cancers.
“This finding means we can better identify children who are most susceptible to radiation-induced cancers before treatment begins and modify their care to prevent this serious long-term complication,” Onel said in a statement. “Luckily our options for Hodgkin’s are broad enough that we can find ways to control the initial disease without relying on radiation therapy.”
Image: Best, T. et al. Nat. Med. doi:10.1038/nm.2407 (2011).