Peto’s Paradox: Can Cancer Get Cancer?

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Around 100 billion cells are created each day in the human body, and a mutation occurs in around 1 in every 100 million divisions. To put things into perspective, that’s 1000 cell divisions and 1000 opportunities each day for cell division to go horribly wrong, and over the course of a lifetime, it only gets worse.

Hidden deep within the cells of our body is our DNA, shielded by the protective double membrane of the nucleus, and yet another membrane at the outer edge of every cell. It is this double-edged DNA that holds the key to life, yet also our very own undoing. Mutations are random, spontaneous changes in the base sequences of our DNA, and a mutation at the right place could mean big trouble. [1]

Most of the time, a mutation that has the potential to be deadly is recognised by the cell, and the cell is tagged for destruction. But as is always the case with nature, there are exceptions, and if certain mutations are able to slip the net, the result could be fatal.

Mutations in our ‘proto-oncogenes’ may result in the cell losing the ability to kill itself, and a deadly cascade of mutations follow, leading to the cell being able to hide from your immune system, divide uncontrollably and hijack essential resources. [2]

Luckily, these evil mutations have an equally as powerful adversary, called ‘tumor suppressor’ genes. These are able to help fix these mutations and signal for the cell to die if it is beyond repair. However, even these tumour suppressor genes are unable to provide complete immunity against cancers. [3][4]

With all this in mind, you’d expect it to be more common for larger organisms with more cells to have more tumours, since there are more cell divisions which have the potential to go wrong. But Sir Richard Peto, an English statistician and epidemiologist, came across a startling observation during his research. He noticed that across nature, it was generally the smaller organisms which had higher incidences of cancer, and that larger organisms (such as whales and elephants), had next to no cases of cancer. As such, he was credited with this phenomenon’s discovery and it was named ‘Peto’s Paradox.’ [2]

There have been many theories which have attempted to unpick and uncover the reasoning behind this puzzling phenomenon, and the three most widely accepted theories are as follows.

The first theory suggests that as single-cellular organisms evolved into more complex organisms, only the ones with a sufficient number of ‘tumor suppressor’ genes present in their DNA were able to survive, and thus the process of cancer-checking became more and more rigorous throughout evolution. [3]

The second theory, and the one that you’ve all been waiting for, lies in the title – can cancer get cancer? Cancer cells are inherently selfish, and they rob the body of its essential nutrients so that they are able to grow themselves. However, these highly unstable cancer cells are susceptible to even more mutations than the common cell, and as a result, they have the ability to mutate to such an extent that a new cell may see itself as different from the original cancer, and use its evil powers against its own ancestors. This new type of cancer is called a ‘hyper tumour,’ and it works to cut off the blood supply to its previous generations, starving them of the nutrients they need for growth and survival. [3][5]

The third and final theory to be uncovered in this article takes a different approach to animals – it judges animals by their metabolic rate instead of their size. As warm blooded organisms get smaller, they generally seem to exhibit higher metabolic rates, as their increased surface area to volume ratio also results in increased heat loss, so smaller organisms are forced to respire more in order to replace this lost heat. In essence, this higher metabolic rate and higher frequency of reactions in the body may result in more opportunities for cancer to occur, and a higher incidence of cancer in smaller organisms. [6]

Peto’s Paradox presents us with an interesting challenge, and one which many theories have tried to unpick, but there still remains no widely accepted theory which gives a fitting response to this baffling observation.


References

  1. Elizabeth Sprouse (2010) “What causes DNA mutation?” Last accessed: 2 May 2020: https://science.howstuffworks.com/life/genetic/dna-mutation.htm
  2. Wikipedia, “Peto’s Paradox.” Last accessed: 18 April 2020: https://en.wikipedia.org/w/index.php?title=Peto%27s_paradox&action=history
  3. Kurzgesagt (2020), “Why Blue Whales Don’t Get Cancer – Peto’s Paradox.” Last accessed: 1 March 2020: https://www.youtube.com/watch?v=1AElONvi9WQ
  4. Sal Khan (2009), “Cancer, Cells, MCAT, Khan Academy” Last accessed: 30 September 2009: https://www.youtube.com/watch?v=RZhL7LDPk8w
  5. Matt Kaplan (2007), “Are big beasts’ cancers self defeating?” https://www.nature.com/news/2007/070730/full/070730-3.html
  6. Biology Stack Exchange (2015), “Why do mice have a higher metabolic rate than humans?” Last Accessed: 23 January 2019: https://biology.stackexchange.com/questions/40281/why-do-mice-have-a-higher-metabolic-rate-than-humans

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