The Student Room Group

How is cancer even possible?

For cancer to develop many mutations (genomic instability) are required culminating in a mutation in a gene controlling cell division such that the cell can’t stop dividing.

But there are about 125 different pairs of DNA repair genes in humans. So for example a smoker would have to develop mutations all 125 repair genes plus the 125 copies that’s 250, of those genes to develop sufficient genomic instability for a mutation in a proto oncogene to be even possible. Then that mutation must occur in a structural part of the gene affecting the final shape of the protein resulting in it being permanently switched on. With a tumour suppressor gene both copies would have to be damaged.
All the time DNA repair genes are being repaired by neighbouring repair genes.

Going by those statistics, how can it be that cancer affects 1 in 3 people surely it should be a lot rarer.
Reply 1
i’m not smart enough to understand what you just said
Humans have so many DNA repair genes because DNA can get damaged in a ton of different ways, chemically speaking. The proteins that do that work are each very specialised in the kind of damage they can repair. If any one DNA repair gene gets knocked out in a lineage of cells, it cripples that lineage's ability to repair that kind of damage. And then that kind of damage will begin to accumulate.

A mutation isn't the same thing as damage to DNA (although damage to DNA risk causing a mutation down the line). A mutation just means that the sequence of bases in the DNA has changed, and the cell has no real mechanism for telling when this has happened. When real damage occurs - i.e. when the phosphodiester backbone of DNA is broken, or when bases that aren't normally used in DNA are incorporated, or when random junk gets attached to DNA - then the cell realises that has to be fixed. But if it's just a change to a base, that's very subtle and easily missed. There's no one true correct genome.

When you consider the number of cells in the entire body all frantically replicating and doing things with their DNA in parallel, the chance of ALL of them doing it flawlessly become very very low, even if there are very good mechanisms for mistake prevention and repair.
How can life exist?
Also, your arguments about where a gene has to be damaged don't necessarily hold up. Surrounding and interspersed with most genes are regulatory elements, and if those get messed up in the right way, they can cause a gene to no longer be expressed, or to be expressed enormously too much.

Finally there are some genes that are super mutagenic if they go wrong. This one takes a little explaining. Basically, the immune system (and specifically B cells) produces antibodies with a highly variable region at one end. Each B cell produces a different shape of antibody, and the shape of that part of the antibody is determined randomly. The way this is done is, there's a protein whose job it is to make random alterations to that part of the gene for the antibody. It's tightly regulated to only make random changes to that gene, and it's only turned on in B cells for a short time in their development from their progenitor cells. But again, if that protein's regulatory elements take a hit in the right way, it can be turned on in some random cell in your colon (for example) where it will just make random changes anywhere it likes in the genome, continuously.
(edited 2 years ago)

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