Study May Explain Fewer Cancers in Down Syndrome

Increased expression of genes on chromosome 21 reduces angiogenesis in mice

FRIDAY, May 22 (HealthDay News) -- Increased expression of at least one gene on the extra copy of chromosome 21 in patients with Down syndrome reduces angiogenesis and may explain why these patients have a lower incidence of cancer and other diseases, according to a study published online May 20 in Nature.

Kwan-Hyuck Baek, Ph.D., from Children's Hospital in Boston, and colleagues examined whether increased expression of the Down syndrome candidate region-1 (Dscr1) gene, which encodes a negative regulator of an angiogenic pathway that operates via the calcineurin pathway, on the extra copy of chromosome 21 could explain the lower incidence of many cancer types and other angiogenesis-related diseases in patients with Down syndrome.

The researchers found that modestly increased expression of DSCR1 suppressed tumor growth in mice, with reduced tumor angiogenesis due to inhibition of signaling via calcineurin. Reducing calcineurin activity through increased expression of DSCR1 and another chromosome 21 gene, DYRK1A, dramatically reduced angiogenesis.

"These data provide a mechanism for the reduced cancer incidence in Down syndrome and identifies the calcineurin signaling pathway, and its regulators DSCR1 and DYRK1A, as potential therapeutic targets in cancers arising in all individuals," Baek and colleagues conclude.

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