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People with Down's syndrome, a disorder caused by having an extra copy of all or part of chromosome 21, tend to have lower-than-average cognitive ability and several characteristic physical features, as well as a shorter lifespan. But, much to the puzzlement of scientists, they are also less likely to develop solid cancers — tumours that form in tissues or organs. Theories proposed to explain this phenomenon include the possibility that many individuals with Down's syndrome die too early for such cancers to emerge, or that they aren't exposed to environmental risk factors or to stress and pressure, which have been linked to cancer. But Sandra Ryeom at the Children's Hospital Boston in Massachusetts and her team have discovered a biological basis for the protective effect of the disorder. Using mouse models, they found that the low solid-cancer rate is attributable at least in part to an extra copy of a gene whose product blocks the formation of new blood vessels — a process called angiogenesis — that typically feed tumours (see page 1126). Ryeom tells Nature more.

How does this gene block angiogenesis?

We learned that DSCR1, a protein encoded by a gene on chromosome 21, suppresses one of the signals needed for new blood vessels to grow. When tumours are starting to form, they send out signals for blood-vessel growth. Humans can't usually fight that signal — it overrides the normal complement of DSCR1 that most of us have. But people with Down's syndrome have three copies of the gene, and we think that contributes to an ability to resist the tumour's signal.

Were you surprised by your findings?

Yes. When you do studies of cells in culture, you might express a gene 10,000-fold more than in its natural state to determine its function. But the mice we used had just one extra copy of the DSCR1 gene and had more than 50% more DSCR1 protein than did the non-Down's-syndrome models. The question was whether that extra amount would be enough to shut down angiogenesis. It was.

What does this mean for human cancers?

We've learned from earlier clinical trials of anti-angiogenic agents that stopping the formation of new blood vessels once a cancer has taken root may come too late to arrest tumour development. We think that there is potential to develop an anti-angiogenic pill that could be taken every day — long before any cancer cells might begin to form — to stop tumours from growing in the first place. If we can show that DSCR1 blocks angiogenesis in the long term and has no side effects in mice, we will pass it on to industry. We're pursuing this now.