People with Down syndrome suffer cancer less than most other people and a study in mice published on Wednesday gives one possible explanation — they produce higher levels of a certain protein.
The protein may keep tumors from growing, and this finding may help in the development of new cancer drugs, the team at Johns Hopkins University in Baltimore reported.
Dr. Roger Reeves of Johns Hopkins and colleagues found a gene called Ets2 protected mice from colon cancer. Writing in the journal Nature, Reeves and colleagues said they used mice bred to develop colon cancer at extreme rates, and genetically engineered them to produce extra amounts of Ets2.
They said the more Ets2 the mice had, the less likely they were to develop colon cancer.
The secret lies in having an extra copy of chromosome 21. People with Down syndrome have three copies of the chromosome instead of the usual two.
That gives them extra copies of all the genes on chromosome 21 and of the proteins that these genes produce.
The effects are well known — people with Downs suffer from mental retardation, have distinct facial and other physical characteristics and a higher risk of some diseases.
But not cancer, said Dr. Judah Folkman, a cancer expert at Children’s Hospital and Harvard Medical School in Boston. Ets2, which is found on chromosome 21, may help explain why.
“They are protected against cancer and also atherosclerosis and diabetic retinopathy,” Folkman, who was not associated with the research, said in a telephone interview.
Diabetic retinopathy can cause blindness in people with diabetes and, like atherosclerosis, is associated with blood vessel function.
Starving tumors
Folkman discovered a protein called endostatin that kick-started a field of cancer drugs called angiogenesis inhibitors. They starve a tumor by stopping it from creating blood vessels to nourish itself.
The basic biological mechanism, which affects blood vessel function and growth, may also underlie other so-called vascular diseases such as atherosclerosis, Folkman said.
Folkman and other researchers believe people with Down produce extra endostatin naturally, but also that other genes play an important role. Ets2 appears to be one of them.
“It is turning out to be very important because it gives a strong clinical clue that suggests some humans may be protected against cancer,” Folkman said.
“Down syndrome is always considered a tragedy for families. But on the other hand, they bring this huge clinical clue,” Folkman said. The genes that protect against cancer appear to be separate from the genes known to cause mental retardation, he added.
“In medical school in 1953 we were taught — ’oh, by the way, Down syndrome individuals are protected against cancer’. Everybody asked why and they said, ’We think it is because they don’t live long enough (to develop it),”’ Folkman said.
But now. Down patients live into their 70s and they still develop cancer at a lower rate, he said.
Dr. David Threadgill of the University of North Carolina agreed that Ets2 might be used as the basis of a drug, but said far more research is needed because the protein also appears to help cancer spread, or metastasize, when it does develop.
“So therapeutic use of potential drugs with Ets2-like activity to reduce tumor incidence may have limited value, because a side effect of such drugs could be increased efficiency of metastasis,” Threadgill wrote in a commentary.
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