What images and thoughts come to your mind when you think of Down syndrome?
Do you think of cognitive disabilities, short stature and contagious smiles? There is something that you are probably not thinking about: Our friends and relatives with Down syndrome may hold a cure for cancer.
Down syndrome is caused by an extra copy of chromosome 21. Instead of inheriting just two copies of every chromosome, one from each parent, individuals with Down syndrome carry a third copy of chromosome 21. This chromosome is very small compared with other chromosomes, and it carries only a few hundred of the 20,000-plus genes in every human cell. However, an extra copy of this tiny piece of DNA suffices to cause all the features of Down syndrome, including but not restricted to intellectual disabilities, short stature, congenital heart defects and increased risk of developing Alzheimer's disease.
Remarkably, people with Down syndrome have an increased incidence of leukemia but a much lower incidence of solid tissue tumors. What is it about the extra copy of chromosome 21 that protects them from solid tumors but predisposes them to blood cancers?
One hypothesis in this research field is that chromosome 21 carries a few cancer-protective genes that, when in an extra dose, prevent the growth of solid tumors. The hunt for these genes is an area of active research, and scientists have already identified at least two "tumor suppressor" genes that work by preventing the formation of new blood vessels around an actively growing solid tumor. The process of blood vessel formation, known as angiogenesis, is tightly controlled by pro- and anti-angiogenic genes, and we know now that two potent anti-angiogenic genes are on chromosome 21. Thus, the additional copy of these genes in people with Down syndrome would prevent the irrigation of incipient tumors, effectively starving them of oxygen and nutrients. Interestingly, the growth of leukemias is not really restricted by angiogenesis, because these cancers are already circulating freely in the blood.
A second interesting idea is that the extra chromosome somehow prevents stem cells from dividing properly, so cancer cells that happen to occur, which resemble stem cells in many ways, fail to form a tumor.
But how do we explain then the increased risk of leukemias? Interestingly, scientists have noticed that in many leukemia patients not affected by Down syndrome, a small piece of chromosome 21 is nonetheless "amplified." The leukemia cells in these children make many copies of this specific fragment of DNA in chromosome 21, which seems to carry one or more "leukemia oncogenes" (i.e., genes that promote the proliferation of blood cells). At least one well-characterized leukemia-promoting gene is located in this region of chromosome 21.
Therefore, our friends and relatives with Down syndrome are, even if unintentionally, enabling discoveries about how cancers develop and how to combat them. Being the most common chromosomal disorder in the population, affecting approximately 1 in 700 newborns, Down syndrome provides a unique opportunity to advance not only cancer research but many other areas of biomedical research, such as Alzheimer's disease and congenital heart defects.
From an epidemiological standpoint, the 400,000 individuals with Down syndrome living in the U.S.A. today constitute a potential gold mine for scientific discoveries. They may carry the secrets that unlock cancer and Alzheimer's, yet we know very little about them, as they have been clearly underserved by the scientific enterprise in general and federal funding agencies in particular.
In 2012, the National Institute of Health spent only 50 research dollars per individual with Down syndrome, seven times less than what was spent on people with multiple sclerosis, and 57 times less than what was spent on people with cystic fibrosis. Fortunately, recent developments in the philanthropy sector are increasing awareness and funding for Down syndrome research, such as the creation of the Linda Crnic Institute for Down Syndrome.
As is often the case in science, the solutions to one problem arise from the study of a seemingly unrelated problem. Next time you meet a person with Down syndrome, say thank you, because he or she may enable the cure for common health issues that will affect you and those you love.