Science Surgery: ‘Could more cancers be caused by inherited faulty genes than we now think?’

Our Science Surgery series answers your cancer science questions.

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Victoria asked: ‘Is it possible that more cancers are caused by inherited faulty genes than we now think?’

To get to the bottom of this, we spoke to one of our experts on genetics and cancer risk, Professor Douglas Easton. It turns out the short answer is: yes. Because as scientists carry out further in-depth research, it’s possible that we’ll find more faulty genes that we didn’t know about. Before getting to the important nitty gritty though, we need to highlight the differences between faulty genes that can be inherited and those that can’t, and set the scene.

What’s in a gene?

Faulty genes, or more generally changes to DNA, can only be passed down through families if they’re in a person’s sex cells – their sperm or eggs. That’s because these cells develop into that person’s children. If a genetic change crops up during a person’s lifetime in other parts of the body, like changes in a lung cell due to smoking, then this can’t be passed on to their children.

Even if a fault that raises the risk of cancer is passed on through families, that doesn’t mean the person inheriting it will definitely get cancer. Their risk depends on the kind of fault it is.

“Broadly speaking, there are 3 different types of inherited genetic changes,” says Professor Easton, from our Cambridge Cancer Centre.

“There are some genes where inherited faults give a person a high risk of developing certain cancers, with classic examples being the faulty BRCA1 and BRCA2 genes.”

These particular ‘high-risk’ genetic changes raise the risk of breast and ovarian cancers, but different faulty genes can raise the risk of other cancers, like bowel cancer. The risk that a person with one of these genetic faults will develop cancer also depends on their age, something we covered recently for the BRCA genes.

“The proportion of cancers due to this type of genetic fault is unlikely to be more than 5%,” Professor Easton says.

“Most of these genes were found some time ago and we know a lot about them. So we think there’s unlikely to be more of that type.”

1 down, 2 to go

The high-risk genetic changes we’ve just talked about are relatively rare in the general population. But there’s a second type that is far more common. These tend to be very small alterations, single ‘spelling mistakes’ in the billions of letters that make up DNA. Most – if not all – people have such variations.

That’s not cause for alarm though. As Professor Easton says, it’s not a matter of whether a person does or doesn’t have such variations – “it’s how many they have that matters”. That’s because each of these ‘low risk’ variants only slightly raise the odds that a person will develop cancer. But if a person has lots of them, then their risk will be higher.

The 4 ‘letters’ that make up DNA are A, C, T and G. Flickr/CC BY 2.0

So what about the third kind? “They sit somewhere in the middle,” says Professor Easton. They raise a person’s risk by more than the common variations, but not as much as the high-risk genetic faults. This type of genetic change also tends to be uncommon.

As we mentioned earlier, scientists think it’s unlikely they’ll find any more high-risk genes like the BRCA1 faults, which they’ve tracked down by following families that have a history of certain cancers and looking for shared genetic features. It’s the other two types that may prove more common than we currently think.

That’s because these are harder to identify in the first place. Rather than homing in on changes to particular genes that are shared within families, scientists need to plough their way through all of the DNA that a person has to find these subtle changes. Not only that, but they have to do this in thousands of people to confirm that they’re linked with cancer. That’s a big job. But it’s something that’s becoming quicker and easier as DNA-reading machines get better and more sophisticated.

As the technology improves, and bigger studies can be carried out, then more of these variations will appear.

So what’s the take home message?

Professor Easton sums it up nicely for us.

“As we find out more through research, the proportion of cancers that we can explain by inherited genetic changes will likely continue to go up as it already has in recent years,” he says.

“The proportion itself won’t change though; it’s the proportion we understand that may change. But there’s a limit as to how much it can increase by. Lifestyle, and chance, as well as inherited genetic changes, are important in determining who gets cancer.”

Exactly how much the proportion might rise by is impossible to say. We’ll only start to find these answers as scientists dig deeper and deeper. So for the moment, it’s a case of wait and see.

Justine

We’d like to thank Victoria for asking us this question. If you’d like to ask us something, email [email protected], leaving your first name and location (optional).