Growing Pains: Why are Blood and Brain Cancers Dominant in Children?

By Bryn Livingston, PhD candidate and RIOT member

About one third of pediatric cancer cases in Canada are diagnosed as leukemia, and another quarter of cases are brain and central nervous system cancers. As a result, over half of all pediatric cancers are blood or brain cancers, and these numbers are reflected globally. The makeup of adult cancer diagnoses is very different, with the most common being breast, prostate, colorectal, and lung cancers. Why is there such a difference? To understand the prominent theories, it’s important to understand a bit about how cancer arises and how this process differs in children and adults.

A recap : Understanding what causes cancer
We can most simply define cancer as a group of abnormal cells which divide uncontrollably. Healthy cells only divide when the body signals to them that there is a need, usually during growth or injury repair. Cancer cells, on the other hand, divide as a default, they don’t respond to messages from surrounding tissues telling them to stop, and they avoid cell death. Changes in these cells’ DNA (mutations) cause more cell division and less cell death, among other factors, which lead to cancer.

So, the causes of cancer can be anything that causes mutations in the DNA. There are three main ways that mutations can occur. They can be inherited from our parents, they can be caused by environmental factors called mutagens, such as pollution, smoking, and alcohol, or they can occur randomly. Our cells need to copy their DNA every time they divide so that both new cells will have all the genetic information they need to function, and sometimes they make mistakes in the process.

The most common adult cancers are very rare in children
The most common adult cancers are breast, prostate, lung, and colorectal cancer. One reason that breast and prostate cancers almost never occur in children because cancers in these organs are heavily influenced by hormones, which change dramatically from childhood to adulthood.

Another reason why the most common adult cancers are almost non-existent in children is that environmental factors play a huge role in causing mutations which lead to these cancers. For colorectal cancer, some of the primary risk factors are alcohol, processed and red meats, as well as Type II diabetes. For lung cancer, they include smoking, air pollution, and occupational exposure to chemical fumes. Some of these factors, like smoking and alcohol, are things that children are not often exposed to, but some, like air pollution, affect people regardless of age. So, why isn’t air pollution causing lung cancer to be prevalent in children?

Mutations are random; most of them have no effect on genes involved in cell division, cell survival, or any other characteristic of cancer. Usually, it takes a long period of time to accumulate enough mutations by chance affecting relevant genes to cause cancer. Children haven’t lived long enough to accumulate the number of mutations needed to cause the most common adult cancers. This is also one of the reasons that cancer in general is more common in older adults.

Childhood cancers occur in vulnerable tissues and stages of development
Why does brain and blood cancer persist in children, despite the lack of environmentally induced mutations? Remember that there are 3 main causes of mutations: heredity, environmental mutagens, and random errors in DNA replication. One might reason that if environmental mutagens are not responsible, then hereditary mutations must be causing pediatric cancers. However, only a small minority of pediatric cancer cases arise from an identifiable inherited mutation. Most pediatric cancer cases cannot be attributed to specific hereditary or environmental factors.

If most pediatric cancers are not caused by hereditary or environmentally induced mutations, we’re left with random errors in DNA replication. As you know, it usually takes many years to accumulate enough mutations in relevant genes to cause cancer. Pediatric cancers are an exception to this rule; they exhibit significantly fewer mutations than adult cancers.

Childhood cancers arise from tissues in vulnerable developmental states. During development, humans grow from a single cell to a fully-grown adult with about 30 trillion cells. All these cells must be produced through cell division, so the first 18 years of life, and especially periods of peak growth such as embryonic development, are periods of increased cell division. There are even certain cell populations in the developing embryo which don’t exist in the adult body, and whose primary function is cell division. They are like little factories, pumping out new cells for the developing body to use to build itself.

These pockets of rapidly dividing cells are especially vulnerable to transformation into cancer cells because they already have some of the required characteristics, such as increased cell division and survival. Because of this vulnerability, these cells don’t need a lifetime of mutations to become cancerous. They only need a few, and because cells need to copy their DNA every time they divide, these rapidly dividing cell populations have more opportunities to make mistakes.

How does this result in a prevalence of blood and brain tumours in children?
Some cell types and tissues are good at replenishing themselves when needed. Think of skin cells as an example. When you get a cut, your skin cells temporarily turn on their cell division mechanisms to fill in the gap. Adult neurons, however, are one of the least regenerative cell types in the body. This is why strokes usually have permanent effects. Adult neurons don’t divide frequently and are therefore not vulnerable to transformation into cancer cells.

However, the embryonic brain contains pockets of rapidly dividing “cell factories” working to produce all the neurons in the brain. The most common type of pediatric brain cancer, medulloblastoma, arises from some particularly important “cell factories” that are responsible for producing more than half of the neurons in the entire brain through cell division.

Unlike neurons, blood cells are replenished regularly in both children and adults, and this makes them more vulnerable to transformation into cancer. What’s more, blood cells represent over 80% of the cells in the human body. By imagining the level of cell division required to produce that many cells, it becomes clear why cancer arises in blood cells during childhood without requiring a lifetime of cancer-causing mutations. In this way, blood cells can be vulnerable to transformation into cancer cells in a similar way to embryonic “cell factories.”

Understanding cancer across the ages: from childhood to adulthood
The reasons for the prevalence of certain types of cancer in different age groups depend on the cancer type. Some prefer specific hormonal environments, are susceptible to environmental mutagens which affect different demographics, require time to accumulate mutations, or arise from temporary cell populations which only exist at certain stages of life. Still, other cancer types have unique reasons for peaking in incidence at different ages. The peak age of incidence for pediatric bone tumours is around 15 years, coinciding with growth spurts (and the cell division behind them!) during adolescence.

Cancer is most common in older adults because environmental mutagens are an important factor in causing cancer, and older adults simply have more exposure to mutagens, and more time for mutations to accumulate. When cancer occurs in children, it arises from tissues which already exhibit the cancer-like traits of more cell division and less cell death, and therefore don’t need to accumulate a lifetime of mutations to become cancerous.

Understanding the biology of these vulnerable cell populations and the process of their transformation into cancer cells is an active area of research. Understanding these processes can help researchers exploit them and could be key to preventing and treating childhood cancers in more targeted ways.

Bryn Livingston is a PhD candidate studying the molecular drivers of pediatric brain cancer at the SickKids Research Institute. She is also Co-President of the Toronto Science Policy Network, a student group which organizes events and campaigns centred around helping the University of Toronto community learn about and engage with science policy. Bryn has a strong interest in accurate and accessible science communication and is a volunteer presenter with the Toronto RIOT team. In this role she has written and presented talks on the basics of cancer biology to diverse audiences including community members impacted by cancer, as well as high school students.

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