DNA mutations and cancer- What causes this to happen?
In the most simple explanation, it’s all in our DNA. Inside every cell is our DNA. Packed into our 46 chromosomes are the instructions that tell each cell what to do. Do you have brown eyes? That’s because you have a gene that instructs your pigment cells in the eyes to be brown. Blonde hair? Ditto. There are instructions for everything. Where a cell should be, when it should grow, when it should die, where to stay put, what to do. Your colon cells know to live in the colon, make mucus, and absorb fluid because they are commanded to by your DNA. You can think of it almost like a computer program or operating system for the cell, written in the approximately 3 billion letters in our DNA.
The problem is, that stuff is fragile. Our DNA gets broken, mutates, and has all kinds of nasty things done to it. And every time a cell divides, it has to perfectly, faithfully copy the DNA. Think about the massive potential for mischief:
- Control mechanisms coded in our DNA
- Billions of base pairs of DNA
- In trillions of cells in the body
- Dividing enough times to last 100+ years……
Well, sometimes the DNA has mistakes introduced into it. Consider the example of copying a book by hand- you might sometimes mistakenly copy “the” when you meant to say “then”. Or “here” when you meant to say “hear.” Same thing happens when our DNA is duplicated. That “mistake” in the DNA is called a mutation. We acquire them constantly throughout our lives. The longer we live, the more mutations we accumulate. The more cells divide, the more chances there are for mutations to occur.
Luckily many of the mutations are harmless. We have lots of DNA that doesn’t do very much or is leftover “junk” DNA. If you mutate that, nothing bad happens. Sometimes the mutations are harmless- like mutating the gene for brown eyes in a colon cell- nothing bad happens there.
However, if you mutate the gene that tells a cell “only grow if…” and now that gene says “grow… grow…. Grow…” now you have a problem. If that cell gets a second mutation and now it can’t die off, the problem is worse. If that cell than gets a third mutation that now teaches it how to invade… well that’s where cancer comes from.
So cancers are acquired; they come from mutations we pick up over a lifetime. It takes a while- a on- in- a- billion mutation followed by another one, followed by another, and so on. Get enough of them, you have a cancer.
So this explains a few things. Most cancers are more common the older we get- that’s because we’ve lived longer and have more chances to acquire mutations. Most cancers happen in tissues that divide the fastest (breast, colon, lung, etc) but MUCH more rare in cells that don’t (heart) or much more slowly (bone, nerve) grow and divide.
This behavior also explains certain things that can increase our risk of cancer. Tobacco smoke contains 4000 different chemicals, at least 69 of which can directly mutate DNA (according to the CDC’s website). In certain inherited cancer syndromes (such as the BRCA inherited breast and ovary cancer syndromes), we lose the ability to repair DNA damage, so more mutations occur, more quickly. Certain viruses (for example HPV virus in the case of cervix cancer) can cause mutations and DNA damage when they infect cells.
Here’s how I think of it- consider each chance at a mutation as similar to buying a lottery ticket once a week (although the bad kind of lottery). For example, in the “Powerball” lottery, you are incredibly unlikely to “win” the lottery with any given ticket (1 in 175 million); but…. You can imagine that if you played the lottery 175 million weeks in a row (the equivalent of almost 340,000 years), your chances of matching the lottery at some point would be rather high. OR- if you purchased 1 million lottery tickets a week, your odds would also go up.
So we can think of age and normal cell division being similar to how many weeks one plays the lotto; we can think of known risk factors for cancer (like smoking) as buying LOTS more tickets each week. The two both contribute to cancer risk.
So which risk is more important? Although it’s a little hard to be exactly sure and prove, we think that the type of cells (i.e. natural growth rate of the cells) and age are the far more important issues for most cancers. One recent controversial study (http://www.hopkinsmedicine.org/news/media/releases/bad_luck_of_random_mutations_plays_predominant_role_in_cancer_study_shows) suggested that about 2/3 of our cancer risk is due to “bad luck”, i.e. the random mutations out of our control, rather than an environmental exposure.
That said, even if completely true, 1/3 of our cancer risk being due to an identifiable cause is still a big deal. For example, even though 15% of lung cancer patients are never- smokers, the remainder of cases occur in current or former smokers; our cancer burden would still be less if smoking was eliminated. So we still should have a good diet, don’t smoke, exercise appropriately.
I’ll take a break from the “What is cancer” and basics series for a few weeks, as there’s lots of exciting stuff to cover from the recent ASCO 2015 meeting. Please feel free to email or comment for other topics to cover in the series in the meantime.