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Down syndrome opens new window on cancer

Down syndrome opens new window on cancer
People with Down syndrome confront a wide range of health challenges, including mental retardation, congenital heart disease and hearing loss.

By Liz Szabo, USA TODAY

People with Down syndrome confront a wide range of health challenges, including mental retardation, congenital heart disease and hearing loss. Yet doctors have long wondered why this community is protected from one of the most devastating illnesses: cancer.

Although people with Down syndrome are at increased risk for leukemia, they rarely develop solid tumors, such as cancers of the breast or colon, says Sandra Ryeom, a researcher at Children's Hospital Boston and author of a study published online Wednesday in Nature. In a study of 17,800 people with the disorder, the mortality rate from cancer was less than 10% of what doctors would expect to see in a general population.

In the past, doctors assumed that people with Down syndrome simply didn't live long enough to develop solid cancers, because many died in their 30s, Ryeom says. Yet children with the disorder don't develop common pediatric cancers, either, such as neuroblastoma or bone tumors.

The answer to the mystery probably lies on chromosome 21. People with Down syndrome have three copies of the chromosome instead of two. That extra chromosome — and extra copies of disease-causing genes — are responsible for many of their health problems. But researchers suspected that the extra chromosome may protect them indirectly by preventing tumors from growing new blood vessels, she says.

Tumors need a blood supply so they can grow beyond a microscopic clump of cells, Ryeom says.

In experiments in mice and in human cells in lab dishes, Ryeom and her colleagues found two genes on chromosome 21 that block this process, called angiogenesis. She suspects there may be several additional genes that block angiogenesis, as well.

Interestingly, angiogenesis isn't involved in leukemia, the cancer of the white blood cells that's more common in Down syndrome patients, says Jessica Pollard, a pediatric oncologist at Seattle Children's Hospital not involved in the study.

Doctors already treat cancer with a variety of anti-angiogenic drugs. The first of this new class of drugs, Avastin, was approved in 2004.

Ryeom is trying to develop additional cancer therapies based on her research.

Roger Reeves, a professor at Johns Hopkins University Medical School, says he's working on a drug based on another anti-angiogenesis gene on chromosome 21, called endostatin. Doctors already are testing that drug in humans.

Pollard describes Ryeom's findings as intriguing but says researchers need to do more human studies.

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