Scientists have known for over ten years that people with Down’s syndrome experience reduced rates of most types of cancer.
Down’s syndrome sufferers have an extra chromosome 21. This additional genetic material leads to a variety of health problems including heart defects, reduced cognitive ability and thyroid gland dysfunction.
Cancers of the blood, specifically leukaemia, are also 10-20 times more common in people with Down’s syndrome. But the incidence of solid tumours (which account for the vast majority of cancers) is significantly reduced in the group.
In recent years researchers have begun to explore the reasons behind this trait in the hope of better understanding cancer and so developing more effective treatments.
The late Judah Folkman, cancer researcher at The Children’s Hospital Boston, popularised the theory that reduced rates of cancer seen in Down’s syndrome are likely due to an extra copy of a gene which blocks angiogenesis.
This is the process by which blood vessels grow and is a key factor in the development of cancer. Tumours, just like any other tissue, require nutrients and oxygen to grow and this is provided via the bloodstream. The more readily vessels develop in a person, the more likely they are to develop to feed a growing cancer.
A 2009 paper published in the journal Nature seemed to suggest that an extra copy of a chromosome 21 gene slowed cancer growth in mice. The gene, DSCR1, was thought to work in combination with another chromosome 21 gene to reduce stimulation of blood vessel growth by cancer cells.
Researchers at London’s Centre for Tumour Biology, part of the Barts Cancer Institute, have been exploring the link between Down’s syndrome and cancer further. Marianne Baker, a PhD student who has been working on the project for nearly four years, explained that the team discovered DSCR1 was not in fact responsible for reduced rates of angiogenesis.
The team have also dispelled another common misconception regarding a protein called endostatin which also inhibits the growth of blood vessels.
People with Down’s syndrome have increased levels of endostatin in their blood and many scientists believed this to be a major reason why cancer is less common in the group. The team found, however, that even when endostatin genes were removed from Down’s syndrome mice they still displayed a decreased frequency of tumours.
Marianne and her colleagues believe differences in endothelial cells, which line the interior surface of blood vessels, might be key to understanding how an extra chromosome 21 reduces the risk of cancer. Endothelial cells allow passage of material in and out of the blood stream and regulate how “leaky” the blood vessels are. This affects how cells interact with each other which is important in cancer biology.
There are around 200 genes on chromosome 21. The team have identified DNA sequences specifically associated with endothelial cells and are exploring the effects of increasing and decreasing their expression on cancer rates.
Collaborators in Germany have been looking at a gene called JAM-A which dictates how endothelial cells stick together. Marianne is now moving on to evaluate the importance of JAM-B, a sister gene.
The correlation between Down’s syndrome and cancer is another example of how the study of one condition can provide vital information about seemingly unrelated diseases. As the team’s research continues they hope to inch closer to the long term goal of more effective, targeted cancer treatments.
Image by Phaeton1
Baek, K., Zaslavsky, A., Lynch, R., Britt, C., Okada, Y., Siarey, R., Lensch, M., Park, I., Yoon, S., Minami, T., Korenberg, J., Folkman, J., Daley, G., Aird, W., Galdzicki, Z., & Ryeom, S. (2009). Down’s syndrome suppression of tumour growth and the role of the calcineurin inhibitor DSCR1 Nature, 459 (7250), 1126-1130 DOI: 10.1038/nature08062
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