Peto’s Paradox: Can we better understand cancer?
How are some animals seemingly immune to one of the leading causes of death in the world?
Theoretically, if every cell has an equal chance of becoming cancerous, organisms with more cells should have a higher chance of developing cancer. Sounds reasonable right? Strangely that’s not the case. Peto’s paradox is the lack in correlation between size and risk of cancer.
How do cells become cancerous?
Inside our bodies, there are trillions of cells that form tissue and organs.
Our cells contain:
- A Nucleus- the “🧠” of the cell
- Chromosomes- tightly coiled DNA around histone proteins
- Genes- sections of DNA that codes for specific traits
- DNA- the “recipe book” that contains our unique genetic code
The instructions in DNA code for proteins which is how your body functions!
Sometimes a gene will develop a mutation. There are two main types of genetic mutations that cause cancer.
Acquired mutations- occur when a gene becomes damaged during a person’s life. These are not in every cell in a body. This can be a result of:
- Exposure to harmful chemicals
- Exposure to too much UV radiation
- Your lifestyle (smoking, too much drinking, not eating nutritiously, lack of physical activity) Don’t do it!
- A mistake made during the cell division process
Germline mutation- occurs in the sperm or egg cells. This is inherited directly from your parents and is uncontrollable. As the baby forms, the mutation that was in the original sperm or egg cell passes on into every other cell in your body.
There are three main “drivers” of cancer:
Proto- oncogenes
- Normal protooncogenes regulate cell division and apoptosis (cell death). When proto- oncogenes are mutated, they become oncogenes and allow cells to divide without restriction.
Tumor suppressor genes
- Regular tumor suppressor genes slow down cell division and repair DNA abnormalities. When tumor suppressor genes are damaged, there is nothing stopping the cells from dividing out of control.
DNA repair genes
- These genes are responsible for fixing DNA that is mutated. When DNA repair genes are damaged, many of the mutations are left uncorrected. The combination of the mutations can cause cancer.
Think of a cell like a 🚗. A car requires a gas pedal and a brake pedal to control the speed. The proto- oncogene is like the gas pedal. It is similar to a gas pedal being stuck down, the cells keep diving and dividing. Tumor suppressor genes are like the brake pedal in a car. When the brake stops functioning, there is nothing slowing down the car.
If one or more of the genes are mutated and cell growth goes out of control, you can develop cancer.
Back to Peto’s Paradox:
In general, cell sizes in different species are almost identical. Bigger animals just have more cells and a longer life span than smaller animals. Since smaller animals have less cells and a smaller number of cell divisions throughout their lifetime, it should mean that they should also have a lower chance of something going wrong. Theoretically.
Humans live around 30 times longer and have 1,000 more cells than mice however the rate of cancer is basically the same in both humans and mice. Blue whales have approximately 3,000 more cells than humans but they don’t seem to get cancer at all 🤯.
While there is no definite answer to why this might be, there are some hypotheses that could explain it:
1. More tumor suppressor genes
More tumor suppressor genes would require more mutations to create cancerous cells. This is seen in elephants. Elephants have 20 copies of the tumor suppressor gene TP53. TP53 detects DNA damage that is irreparable and also triggers apoptosis (cell death). Humans on the other hand only have one copy in every gene. Elephants have a mortality rate of 4.81% which is much lower than the human mortality rate of 11–25%.
2. Hyper tumors
A hyper tumor is a second tumor that invades part of the initial cancerous tumor.
- The initial cancer cells multiply out of control
- A new mutation is created and a new tumor forms on top of the initial tumor
- This new tumor needs nutrients and the closest source is the initial cancerous tumor that is right under it.
- The newly formed hyper tumor sucks all the nutrients from the initial tumor, killing it.
- Without a source of energy and nutrients, the hyper tumor dies as well.
This video explains more about the potential causes of Peto’s paradox!
There has not been extensive research put into Peto’s paradox and there is no concrete answer to why it exists. If we could figure out why larger animals tend to be less susceptible to a huge problem humans are facing could introduce us to more ways to treat cancer!
TL;DR
- Cells can become cancerous if they have a mutation that allows them to go through the cell cycle and divide uncontrolled.
- Since every cell has an equal chance of becoming cancerous, organisms with more cells should have a higher cancer rate however this is not the case. This is called Peto’s Paradox.
- There is no definite explanation for Peto’s Paradox but it could be the result of more tumor suppressor genes or hypertumors.
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