Question of the Week

Do foetuses get cancer?

Sun, 9th Dec 2012

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Question

Louis Clement-Harris asked:

Do foetuses get cancer?

 

Their cells divide rapidly, so surely they can make genetic errors and get cancer.

 

Thank you in advance.

 

Louis CH

Answer

Hannah -   Cancer is the unregulated growth of cells and during pregnancy, cells divide very rapidly.  There are mechanisms in place to prevent cancer developing, but as Professor Graham Burton from Cambridge University points outÖEmbryo

Graham -   About 1 in 10,000 babies when they're born will have some sort of tumour, a swelling in the body associated with abnormal growth.  

Thankfully, these are usually what we would call benign in that the cells do not invade into other parts of the body, and so, can be treated usually at the time of birth. 

In terms of true cancer, in terms of uncontrolled proliferation, the other way that a foetus could develop that is if it is transmitted from the mother.  Fortunately again, this is very rare.  Most maternal tumours will not cross the placenta.  The placenta forms a pretty effective barrier to agents that would cause cancer in an adult so that the embryo is in a very protected environment, but will also stop cells from the mother crossing into the foetus.  

But occasionally, we know that there is mixing of the two circulations, the two blood systems, and if the mother has leukaemia or a similar condition, it has been reported that the foetus can develop the same problem.  

Finally of course, the placenta itself can undergo a cancerous change.  This again is very rare.  Itís associated with a very interesting, but curious condition known as hydatidiform mole.

Normally, you would derive half of your chromosomes from the mother and half from the father, but in these cases, all of the chromosomes comes from the father, and this causes very rapid proliferation of the placental tissues, but interestingly, you get very, very small growth of the foetus itself. 

And so, often in these cases, there's no baby to be found at all, just a big mass of placenta.  And because of this rapid proliferation, some of those placental cells can undergo a cancerous change.

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There have been cases where a mother's cancer has crossed the placenta and taken root in the foetus. The foetus' immune system cannot recognise and fight off these "foreign" invaders. http://en.wikipedia.org/wiki/Cancer#Other

Human cells can divide up to about 40-60 times, the Hayflick limit http://en.wikipedia.org/wiki/Hayflick_limit

The average human cell has a mass of 1 nanogram (10-12 kilograms  http://en.wikipedia.org/wiki/Orders_of_magnitude_%28mass%29)...

A 4kg newborn baby has about 4x1012 cells.

Very roughly, this implies around 42 cell divisions from a fertilised egg up to birth

and another 4 divisions from birth to a 64kg adult (ignoring a whole bunch of factors, including wear and tear!)

So an adult cell starting to multiply rapidly would run into the Hayflick limit after around 14 cell divisions, producing about 15000 cells, much less than a milligram (which seems hardly life-threatening)

This seems to give some reasonable cancer protection for an adult, but provides little protection from a cancer starting in a young foetus



It takes somewhere around half-a-dozen important mutations for a cell to evade the Hayflick limit and become a cancer growing out of control. For example:

Disabling error-checking in DNA duplication

Turning off normal tissue growth regulation

Turning on an extra blood supply

Turning on telomerase

Turning off apoptosis
Disabling tumour-suppressor genes
Forming metastasies




The human DNA is around 3.2x109 base pairs, suggesting 1 mutation for every 3 cell divisions.
By the time a cell line reaches 42 divisions, we could expect a random collection of about 14 mutations in each cell, just from copying errors alone.
In the unlikely event that DNA repair mechanisms were completely disabled, the rate of copying errors would increase dramatically:

From the normal level of 2 mutations in 6 divisions

To an astounding 700 million mutations in 6 divisions. This would almost certainly interfere with tumour-suppressing genes (if it didn't kill the cell first).


It is certainly possible for a foetus to develop a cancer, if enough of these mutations disable the critical genes. A cluster of mutations like this could occur in a single cell due to normal rates mutation during cell division up to birth, but it is fairly unlikely.

If a baby inherits some of the well-known cancer genes like BRCA1 or BRCA2 (which are part of the DNA repair mechanism), that already places them 1 or 2 steps down the path to developing a cancer

Stem cells often express telomerase, which removes one more barrier to developing cancer. They divide more, and can build up more copying errors.


Conclusion
There are many causes of infant mortality, but cancer originating in the foetus is well down the list.

However, such a combination of mutations is even more likely to occur and cause a fatal cancer in someone aged 70 or 80, who has a declining immune system, and has been exposed to a lifetime of cell division errors, UV (& other) radiation, viral infections, cigarette smoke and other environmental carcinogens. evan_au, Tue, 4th Dec 2012




https://en.wikipedia.org/wiki/Sacrococcygeal_teratoma

Mutations very early on could cause spontaneous abortion, so the "live birth" statistics are going to be an underestimate. RD, Tue, 4th Dec 2012

Is there anyway that a simple zygote can end up as a cancerous cell in itself? What would that result in? Supercryptid, Wed, 5th Dec 2012

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