Why are patients with Down’s syndrome protected from cancer?

Discovery of novel anti-tumor proteins in patients with Down’s syndrome.

In a very interesting study published in Nature this month, scientists from Harvard Medical School have zeroed in on a gene that might explain why patients with Down’s syndrome have a very low rate of cancer compared to the general population (Baek et al., 2009).
Down syndrome is one of the most common inherited causes of mental retardation. It occurs with an approximate frequency of 1:700 births. The association between Down's syndrome and decreased cancer incidence had earlier been explored by Harvard's Dr. Judah Folkman who died last year. Dr. Folkman had noticed that cancer is rare among Down's patients, except for leukemia. He studied nearly 18,000 Down's patients and showed that they had 10 percent the expected rate of cancer.
Down’s syndrome is characterized by the presence of an extra copy of chromosome 21 in the genome (trisomy 21). Chromosome 21 has 231 genes in it. Scientists have proposed that a protein coded for by one of the genes on the 21st chromosome called “Down's syndrome candidate region-1” (DSCR1, also known as RCAN1) may explain the low incidence of cancer in Down’s syndrome. This protein inhibits Vascular Endothelial Growth Factor (VEGF). VEGF is one of the many factors that help cancer cells to stimulate formation of new blood vessels (angiogenesis). Inhibition of this factor by DSCR 1 can therefore retard the growth of cancers. People with Down syndrome have three copies of this gene while normal individuals only have two. It was shown that the levels of this protein is higher in patients with Down’s syndrome. In this study, the scientists also developed a mouse model of trisomy 21. The mouse model, like the humans, showed higher levels of DSCR-1 protein, and as expected, was resistant to development of tumors.

It is possible that more genes on the 21st chromosome can have anti-tumor properties that will explain the rarity of cancer in Down’s syndrome. Further research will reveal some of these genes. As of now, researchers say that three new proteins have been identified as potential targets in treatment of cancer. One is DSCR-1 and the others are calcineurin (a protein regulated by DSCR-1) and DYRK1A (a DSCR-1 like protein).

References:
Baek KH, Zaslavsky A, Lynch RC, Britt C, Okada Y, Siarey RJ, Lensch MW, Park IH, Yoon SS, Minami T, Korenberg JR, Folkman J, Daley GQ, Aird WC, Galdzicki Z, Ryeom S (2009) Down's syndrome suppression of tumour growth and the role of the calcineurin inhibitor DSCR1. Nature. 2009 May 20.

http://www.ncbi.nlm.nih.gov/pubmed/19458618?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum