Down syndrome’s anti-tumor effect

People with Down syndrome face a heightened risk of developing leukemia (

SN: 12/22/07, p. 402), but some studies hint that people with the condition might be protected against solid-tumor cancers.

A study in mice now shows that the chromosomal abnormality that causes Down syndrome might harbor a genetic aberration that protects against colon cancer.

People with Down syndrome have three copies of chromosome 21 instead of the normal two. One of the genes on chromosome 21 is Ets2. Past research indicated that the protein encoded by Ets2 regulates as many as 200 genes, says study coauthor Roger Reeves, a geneticist at the Johns Hopkins Medical Institutions in Baltimore. He wondered whether Ets2 might exert the reputed anticancer influence.

To test the idea, Reeves and his colleagues crossed mice carrying a mutation known to cause colon cancer with mice that had the third chromosome as well as with others that didn’t. Those with the third chromosome developed roughly half as many tumors as the other mice, the researchers report in the Jan. 3 Nature.

When the researchers scaled back the Ets2 gene to one or two copies instead of three, the mice lost much of their protection against tumors. The findings suggest that the extra proteins encoded by the third Ets2 gene and possibly another nearby gene provide this protective effect, Reeves says.

“We’re now testing this in other kinds of cancers,” he says, “and looking for small molecules that elevate Ets2 expression.”