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People with Down's syndrome rarely get most kinds of cancer and US researchers have nailed down one reason why - they have extra copies of a gene that helps keep tumours from feeding themselves.
The findings could lead to new treatments for cancer, the researchers reported in the journal Nature, and further study of Down's patients might reveal more ways to fight tumours.
Pluripotent stem cell
The researchers at Harvard University and elsewhere made use of a new kind of embryonic-like stem cell called an induced pluripotent stem cell or iPS cell. These cells, made from ordinary skin, can be transformed to act like powerful stem cells, the body's master cells.
Using iPS cells from a volunteer with Down's syndrome and mice genetically engineered to have a version of the condition, the researchers pinpointed one gene that protects against tumours.
"It is, perhaps, inspiring that the Down's syndrome population provides us with new insight into mechanisms that regulate cancer growth," they wrote.
Down's syndrome is the most common genetic cause of mental retardation, occurring in 1 out of 700 live births.
The Down's syndrome theory had long been explored by Harvard's Dr Judah Folkman, who died last year. Folkman, whose name is on the study, developed theories about how tumour cells grow blood vessels to nourish themselves in a process called angiogenesis.
Extra genes
Folkman also noticed how rare cancer is among Down's patients, except for leukaemia, and he wondered whether the genes explain why. A study of nearly 18 000 Down's patients showed they had 10% the expected rate of cancer.
People with Down's syndrome have a third copy of chromosome 21, where most people have two copies. The extra copy gives them extra versions of 231 different genes.
"One such gene is Down's syndrome candidate region-1 (DSCR1, also known as RCAN1)," Harvard's Sandra Ryeom and colleagues wrote.
More of a certain protein
This gene codes for a protein that suppresses vascular endothelial growth factor or VEGF - one of the compounds necessary for angiogenesis.
Down's patients have extra amounts of this DSCR1 protein, as do the genetically engineered Down's mice, the researchers showed. Genetically engineered mice with an extra copy of DSCR1 were resistant to tumours.
DSCR1 affects a compound called calcineurin, long a focus of cancer research.
"These data provide a mechanism for the reduced cancer incidence in Down's syndrome," the researchers wrote.
The study also provides three new potential targets for preventing or treating cancer - calcineurin and two genes that regulate it, DSCR1 and DYRK1A, they said.
People with Down's syndrome are also less likely to develop angiogenesis-related diseases such as diabetic retinopathy (an eye disease related to diabetes) and atherosclerosis (hardened arteries), "suggesting that cancer protection ... may be due, in part, to angiogenesis suppression," the researchers wrote.
"Because human chromosome 21 contains over 200 genes, it would be surprising if DSCR1 was the only chromosome 21 gene implicated in tumour suppression in Down's syndrome individuals," they said. – (Maggie Fox/Reuters Health, May 2009)
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