Nazneen Rahman - Cancer gene screen

10 October 2016

Interview with

Nazneen Rahman, The Institute of Cancer Research

Kat - Over the past few years we've witnessed the rise of personalised or precision treatments for cancer - drugs that target the products of faulty genes in cancer cells, as revealed by genetically testing tumours. But what can genetic information tell us about cancer risk, and the chances of developing the disease in the first place? To find out, I spoke to Professor Nazneen Rahman at The Institute of Cancer Research and the Royal Marsden hospital, who has spent her career studying the genetic faults and variations that influence the risk of many types of cancer.

Nazneen - Well the first thing that makes it difficult is cancer is so very common. About one in two, one in three people will get cancer. So everybody has cancer in their family and that's not usually actually due to genetic factors. There are all sorts of different things that lead to us having an increased risk of cancer. So the first thing we're doing when we're sort of doing that is trying to work out how likely it is that inherited factors are going to be relevant. That depends firstly on the type of cancer and then also, of the patterns of cancers in the family.

Kat - So, what would be some kind of classic hereditary cancers that you can pick out?

Nazneen - Well, probably the ones that people know about most are the breast and ovarian cancers. Ovarian cancer in particular, around about one in five ovarian cancers is due to inherited factors usually in the BRCA genes. A lot of people know about that because of Angelina Jolie.

Kat - Yes, the Angelina Jolie gene I believe we must call it.

Nazneen - Don't call it that! So ovarian cancer is one in which genetic inherited factors are making a big impact. Breast cancer is only about 3 or 4 per cent that are due to these inherited factors. But because breast cancer is so common, it ends up being about the same number of cancers per year. About 2,500 of both ovarian and breast cancer per year in the UK are due to inherited factors.

Kat - What else can we tell about an individual's cancer risk from their genetics because we sort of hear about those - if you like to call them, the strong gene factors - things like the BRCA genes? Surely, there are other things in our DNA that maybe more subtly increase or decrease our risk. Can we look for those? What do they do for us?

Nazneen - Yes, we can. I think it's probably more helpful to think about what gives us cancer overall as a whole spectrum of things - genetic, environmental, lifestyle. All of these things are working together to make it more or less likely that a person will get cancer. And there are also chance events in it. so, I think the importance of thinking about those very strongly acting genetic factors particularly in terms of prediction is that if you're at a very high risk of having a particular disease then you're more likely to act upon that than if there's just a slightly increased risk. Again, particularly if you're at a high risk anyway because one in two people will get cancer. So, in terms of really having an impact on the choices that people can make and giving useful information, the higher the risk is, the more likely that's going to lead to meaningful actions for people.

Kat - If say, I was worried about my genetic risk of cancer, what could I find out? How can I go about finding out is there anything in my DNA and what might it mean for me?

Nazneen - I think what we're really trying to do in the UK to really try and give that information through the individuals who first got cancer in the family. So, we're trying to get more and more of this testing happening for cancer patients. One, that allows us to give the cancer patient themselves better tailored information because they've got their cancer because of this genetic risk. But in turn, that means that we can then go out to the people in their immediate family and then more beyond who are at risk of having inherited it so that we can have a much more effective way of getting that information out to the people that needed it. If you actually tested the whole population, that would be pretty ineffective because they're overall in the population. They're sort of rare, only about 1 in 300 of the individuals would have that. So, I think the way in which we're trying to get people to have that information is really by trying to get as much testing done for cancer patients first and then going out through the family through that way.

Kat - So, is it going to be likely at any point that there's like a national cancer screen where everyone can have all their genes looked at? I'm thinking that there are already products where you can get a lot of information about various things in your DNA, how they affect your risk of health. Are we not really at a point of using genetics for widespread population screening?

Nazneen - Not in terms of cancer. There are two reasons for that. One, it doesn't make sense even economically or even scientifically really. There's only a certain number of these mutations in the population. So to survey the whole population to find them is a very inefficient way of doing that. Equally importantly and possibly even more importantly, we don't really know at this point what the risk of cancer is and that's the critical information. So, if you just test a random member of the population and find they have a mutation in a gene that can increase the risk of cancer, the natural question is, "how much is my cancer risk now?"

Kat - Will it happen? That's the big one.

Nazneen - And that sort of information we haven't got because we haven't done studies on the population at large. What we do knowledge is that cancer risk is not a definitive value. It's in itself very changeable. So the risk of cancer, even of the same mutation, will vary depending on all sorts of contextual things about that individual. So we actually haven't got enough information to give, clear information to people if they were having testing in that context. We still need to do these studies.

Kat - In terms of your own work, you're particularly focusing on ovarian cancer. What are you trying to do to unpack this disease more?

Nazneen - Well ovarian cancer actually for us is a kind of exemplar really of the whole system. The system really is about making genetic testing routinely and easily available where it can have a beneficial impact for cancer patients and their families. The reason that we chose ovarian cancer was firstly because genetics is important. As I say, one in five individuals with ovarian cancer will have had their ovarian cancer because of an inherited gene mutation. Secondly, it is a disease where there's still a high mortality. And so, anything we can do to try and reduce that and prevent cancer from occurring is very important. And so there, what we're trying to do is making sure that all ovarian cancer patients can have access to the genetic testing so we can find out who has the inherited cause. And that impacts to their treatment, also the ones who don't, that also has impacts on their treatment, so it allows to personalise their treatments. But then also, we can go out to their family members. They can potentially have testing. If they're at higher risk, prevention of ovarian cancer by keyhole surgery after people have completed their families is a very effective way of preventing the cancer occuring in the first place.

Kat - So just removing the ovaries so they can't become cancerous.

Nazneen - Yes, absolutely. So, prevention is always better than cure. Often prevention is extremely difficult because either you can't remove all parts of the body.

Kat - You can't take someone's whole bowel out.

Nazneen - You can't, absolutely. So, sometimes if the risk is high enough, people do have their bowels out. But again, it depends on your risk. It has to be incredibly high for that to be a reasonable strategy. For ovarian cancer, as I say, once people have had their families you can have the ovaries removed by keyhole surgery. And in a situation where you still got a very high mortality and there's no useful screening, a lot of women, over 80 per cent of the women we see if they're at high risk, will choose that option.

Kat - Nazneen Rahman from The Institute of Cancer Research.

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