X-Ray Kin: Radiation risk is hereditary

Susceptibility to radiation-induced tumors runs in families, according to an unusual study.

In the 1950s, Jewish immigrants from North Africa and elsewhere streamed into the new country of Israel. Many arriving children carried a fungal scalp infection called tinea capitis, also known as ringworm. Standard treatment included a quick dose of X rays that zapped the fungus and induced temporary baldness. Unbeknownst to anyone at the time, it also damaged the children’s DNA.

Decades later, some people irradiated as youths developed tumors. Particularly common were meningiomas, noncancerous tumors that grow in the lining of the brain and spinal cord.

“We asked ourselves, ‘Why does a certain person develop meningioma following … irradiation and another does not?'” says Siegal Sadetzki, an epidemiologist at Chaim Sheba Medical Center in Tel Hashomer, Israel. Because tumor rates turned out to be much higher in some families than in others, “we thought the answer must be susceptibility, or genes,” says Sadetzki.

Tinea capitis is highly contagious, and the families involved were relatively large, averaging nearly six children. This provided unique circumstances for testing the idea of genetic susceptibility. If one child had the fungus, then several siblings typically got it and all received the radiation treatment.

Overall, fewer than 1 in 100 irradiated children developed meningioma. However, the researchers found that in the most-susceptible families, four out of five children developed it. “This is really stunning,” says Sadetzki, who reports her group’s findings in the May Lancet Oncology.

Eric Hall, a radiation researcher at Columbia University Medical Center, calls the pattern “an incredible concentration of risk.”

Sadetzki points to one family’s experience as particularly striking: Of seven children, four were irradiated, and all four later developed meningioma. In some susceptible families, Sadetzki and her colleagues also noted radiation-associated cancers such as leukemia.

The new finding “upsets all of our ideas about patient protection [from X rays],” says Hall. If susceptibility differences exist, “most people in the population don’t need to be stringently protected … but the minority should be kept away from any radiation exposure.”

Currently, there is no way to determine which families might be at high risk. “That’s the $60,000 question,” says Hall.

The Israeli team doesn’t yet know which genes account for the increased sensitivity to radiation, but it has collected DNA and is zeroing in on several possible genes. “These are the perfect families [for trying] to locate the genes,” Sadetzki says.

Hall notes that scientists have suspected for years that some people are more radiation sensitive than others. In animals, Hall has identified a handful of genetic variations that might cause radiation sensitivity. The variations occur in certain genes crucial for cellular functions, such as repairing DNA damage, that are disrupted by radiation.

Two candidate genes in people include BRCA1 and BRCA2, says Hall. Mutations in these genes are already well known as risk factors for breast cancer. If future research confirms the BRCA-radiation connection, women carrying the mutations will face a double bind: Getting mammograms to check for early breast cancer might increase their risk for developing the disease.

Says Hall: “We have to figure out the genetics of this.”