Cancer 101: How do growth-control mechanisms break?

This is post number two in my “cancer 101” series. To start at the beginning, please check out yesterday’s post, Cancer 101: What is cancer?  This post is the first half of my answer to “what causes cancer?”

Why do mutations happen?

Yesterday, I explained what cancer is: in short, cells gone rogue. In multicellular organisms, there are lots of control mechanisms that keep cells doing the specific jobs they are assigned in your body, and when those mechanisms break, cells are free to revert to the default condition of life: eat, grow, divide, survive. At all costs. Screw the rest of the body, these rebel cells are free from their chains, and damn it, they’re going to LIVE.

Now, what is key to understand here is that all of those control mechanisms I talked about? They are encoded in the genetic material, in your DNA. There are genes that code for detector proteins that trigger cell death in response to the presence of a virus. There are genes for receptor proteins and signaling proteins involved in receiving signals from outside the cell, things like “growth hormone here, time to grow and divide!” or “you’re bumping into the cell next to you, stop growing now!”. The list of mechanisms is long, but every single one of them depends on the action of molecules that are encoded by the genome.

And when I say encoded, I literally am talking about code: every bit of information needed to build a person is written in the chemical letters adenine, guanine, thymine, and cytosine, or A’s, G’s, T’s, and C’s, for short. Every single cell in your body contains a copy of your entire genome, written in almost incomprehensibly long strings of chemicals. Every time a cell in your body divides, whether in the process of growing from a single fertilized egg to a full human built out of hundreds of different cell types, or in the every-day regeneration necessary to replace short-lived blood cells and intestinal epithelial cells, to heal wounds, to grow hair and fingernails–every time one cell becomes two, it must first copy every.single.letter of the several billion that make up your genome.

In general, our cells are astoundingly good at pulling off this copying job. The basic DNA replicating machinery makes an error roughly once in every 100,000 letters, which when you are copying several billion letters could be considered pretty sloppy. EXCEPT… there is a second system, the “proofreading” system, in your cells that goes back over the new DNA as it is replicated and checks for errors. It is estimated that this editing system corrects 99% of copying errors. And even THAT is not enough… another system catches most of those 1% that get past the first round of editing. What this means is that usually, when your cells divide, the replication process is damn near perfect, letting few, if any, copying errors (changing an “A” to a “T”, for example) per cell division.

That said, JUST from the copying process, even under ideal conditions, mistakes slip through now and then. And your cells don’t just divide once, they divide hundreds or thousands of times. And over time, those mistakes–which biologists call mutations–build up.

But copying errors are only the beginning of the story. In between cell divisions, when your DNA is just hanging out in your cells, it is subject to damage that can also cause mutations. DNA is just a chemical, and like any other chemical it is subject to reactions that can alter its structure.

Some such reactions are caused by forces that come from outside your body–many forms of radiation, including X-rays and UV radiation, are known to cause DNA damage, for instance. There are also countless chemicals, natural and synthetic (‘natural’ chemicals are not magically safe) that can cause DNA damage if your cells are exposed to them. These are the chemicals we typically refer to as “carcinogens”, which is kind of misleading, because they don’t directly cause cancer. They cause DNA damage, which, if not repaired perfectly, leads to mutations, which may or may not lead to cancer down the line.

But some DNA damage is the completely unavoidable result of being alive. Every single one of your cells performs a wide variety of chemical reactions constantly, and some of those reactions have dangerous byproducts that can cause damage to the cell, including DNA damage. For instance, your body is constantly producing, as a consequence of normal metabolism, what we call Reactive Oxygen Species, or ROS’s. And those little jerks just run around reacting with ALL THE THINGS, totally wrecking havoc, if they aren’t swiftly contained.

Of course, our body has mechanisms for mopping up dangerous metabolic byproducts like ROS’s, and for generally dealing with everyday DNA damage. And they are fairly effective, all things considered… but not quite as effective as the mechanisms for stopping copying errors, which are already not perfect.

So bottom line, as you go about your everyday life, you are steadily accumulating mutations in your DNA. You can limit the rate at which they accumulate to some extent, by avoiding certain chemicals and major sources of ionizing and UV radiation,* but it is literally impossible to escape them entirely, provided you like being alive. Inevitably, you will eventually accumulate some of those mutations in genes that are responsible for keeping cell growth under control.

If you are unlucky enough, enough of those control genes will break in the same cell, that it will become cancerous. A wide variety of variables, including genetics, control how soon our luck fails us in this regard, but a lot of it is up to random chance. And even if you do everything right, eventually the odds will fail you. Even if you have a relatively low amount of genetic mutation compared to other humans, you still have some, and if you live long enough, eventually they catch up to you.

Okay, don’t panic. I know that we’ve all been taught that cancer is THE SCARIEST THING EVER, and no one wants to contemplate what I’m telling you, but this is the truth: no one is safe from cancer. Mutations are natural, and so, in the grand scheme of things, is cancer**. In fact, the ONLY reason any of us escapes getting cancer is because something else kills us first***.

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I’ve given you a lot to process, so we’re going to pause here for now. In my next post, I’ll go into a little more detail about what exactly happens when mutations happen and growth-control-mechanisms break down.

*We tend to overestimate the amount of control we have over limiting contact with carcinogens, thinking that if we just eat healthily/naturally and avoid “chemical” products, we’re safe. What we’re missing, when we do this, is that SO MANY chemicals can cause DNA damage, at least under lab conditions. I mean, fuck, it doesn’t matter how bloody “organic” your potatoes are, they still produce acrylamide when you fry them, a chemical that is known to cause cancer when fed to rats… though there is little evidence that humans are capable of consuming anywhere near enough acrylamide from natural sources to make a damn bit of difference. Point being, aside from avoiding a few major sources of carcinogens, fretting about whether every little thing in your environment “causes cancer” is of pretty limited utility. But I’ll have more on this in the “mythbusting” post.

**I know that “cancer is natural” may seem like an incredibly cruel thing to say, especially if you or a loved one has suffered through it. But I did NOT say “cancer is good”, though you may have read it that way because you hear “natural” as a synonym for “good”. It isn’t. This is a fallacy that many of us have learned, and it does not serve us. The world will be a better place when we manage to destroy this misleading line of reasoning.

***This is the main reason we all tend to perceive cancer to be an ever-increasing problem. As modern medicine makes progress on treating or preventing other diseases that used to kill us, more of us are living long enough for our luck to fail.