Professor David Phillips, Kings College London
Kat - “Carcinogen” is a word you might hear in the media, but it basically means “something that causes cancer”, and usually refers to things such as chemicals in our environment or food, or even things like UV radiation from the sun and sunbeds or ionising radiation such as X-rays. To find out more about these damaging agents, and how researchers are figuring out exactly how they cause cancer, I spoke to one of the UK’s leading experts - David Phillips, professor of environmental carcinogenesis at Kings College London.
David - We know that most cancers have an environmental component to them. That something in the environment is causative or a causative factor in the disease. Evidence for this goes back to the 18th century when a London physician noticed that chimney sweepers frequently got cancer of the scrotum and he attributed this to their exposure to soot.
And in the intervening several hundred years, we’ve come a long way into understanding why, because soot contains chemicals that are carcinogenic and these have been identified. In the meantime, we’ve identified a lot of other environmental carcinogens, i.e. chemicals to which we’re exposed environmentally which at least have the potential to cause cancer.
Kat - There's a big book on your desk and it looks like a huge thing listing all sorts of chemicals. Is it possible to put a number on them or can we broadly group carcinogens into different types?
David - Well, we can do both. There's probably several hundred chemicals which are known to be carcinogenic and this can be broadly categorised into various types. For example, tobacco smoke is a very complex mixture of chemicals, but at least 60 of those present are carcinogenic. Air pollution contains some of the same carcinogens, ionising radiation, non-ionising radiation, ultraviolet...
Kat - So, sunlight basically.
David - Yes, sunlight. It’s a cause of skin cancer. Some products that are naturally present in plants, some that are produced by fungi, and many others.
Kat - If say, you were to look at the kind of damage caused by say, tobacco smoke and ultraviolet radiation from the sun, would it look the same or can you distinguish it?
David - Well, there are signatures because when the DNA is damaged, that can lead to errors of replication, when the cell divides and replicates its DNA. And that will lead to changes in the sequence of the DNA which we call a mutation. If a mutation occurs in a critical gene, this can initiate the carcinogenic process. Cells have defence mechanisms against DNA damage. DNA repair mechanisms but sometimes these are bypassed or overwhelmed and mutation can result.
So for example, we now have the ability to sequence the DNA of tumours and it’s been found over the last 15 to 20 years that tumours are full of mutations. The challenge now is to try and identify what those mutations have been caused by. Now, with the advent of whole genome sequencing to a practical level, it’s now possible to sequence the entire genome of an organism whether it’s a tumour or a test cell in the lab, and look at the mutations that have occurred across the whole genome. This may give us a more complete picture and a more diagnostic picture of the patterns of mutation caused by particular agents.
In the last year or so, work at the Sanger Institute in Cambridge has sequenced more around 7,000 different human tumours. They’ve come up with a broad categorisation that there are 21 particular types of mutation pattern that they’ve identified. In many of these cases, we don’t know what's caused but we hope now, that if we can experimentally reproduce these patterns by taking some of the chemical carcinogens that we know or suspect of being carcinogenic, and seeing what type of patterns they produce across the whole genome in a test system, we may be able to identify the actual causative agent in more cases of human cancer.
Kat - So, you're going to take human cells, you take the chemical, you chuck it on it, then you look in the DNA and say, “Oh! That’s signature number 13. That’s what must be linked to that exposure.”
David - Well essentially, it boils down to an experiment that’s as simple as that, but obviously, it will turn out to be a lot more complex I'm sure. But in principle, yes, that’s what we’re hoping to do.
Kat - It seems like an incredibly powerful approach because often, you sort of hear people say, “Well, this type of cancer, we just don’t know what caused it” or “Maybe it was this. Maybe it was my job. Maybe it was something I ate.” Do you think we will be able to narrow down to an individual person’s cancer what might have caused it?
David - That’s the hope, yes. There's already a proof of principle here because it’s now known that many cases of urothelial cancer worldwide can be attributed to ingestion of a plant carcinogen called aristolochic acid. This is present in plants that are accidentally ingested for example in the Balkans, but it’s also a compound that’s been widely used in Chinese traditional medicines. So, large numbers of people have been exposed to this. This produces a particular mutagenic mutation signature in urothelial cancers. Because we know a fair bit about the actual biochemical properties of aristolochic acid itself in experimental system, we can definitively say that in some cases, this pattern is what is seen in the human cancers.
In some cases, it may turn out that the pattern does not match that of the agent. In which case, one can say that that particular cancer, even though we suspect it might be due to the exposure, we can actually rule out that exposure. So, it can work both ways. We may be able to identify what's caused somebody’s cancer, but also, in other cases where we suspect something that have caused it, actually say, “No, it didn’t.”
Kat - That also opens up some cans of worms. You can imagine if someone finds out their cancer has a signature of this chemical, maybe they could sue the person that exposed them to it, or made it, or put in the environment. Do you think there are implications for those kinds of public health issues?
David - Yes, I'm sure there are because one of the problems you have with identifying a cause of somebody’s cancer, if it’s down to something environmental or occupational, is that it’s many decades from potential exposure to disease. And actually, tracking back and saying whether this was in fact the cause of the cancer can be extremely difficult. So, this may actually be quite helpful in actually pinning down whether an occupational or environmental exposure has been the cause or not, yes.
Kat - Working in a field like this where you're talking all the time about carcinogens and nasty chemicals, does it make you paranoid at all?
David - I wouldn’t say paranoid, but I'm as concerned to live in as clean an environment as I can as the next person. So, from that point of view, I’d like to think that I try to avoid, where it’s a matter of personal choice, exposure to carcinogens. But of course in many cases, it isn’t. I live and work in London. London is a mega city. Mega cities have air pollution, so I'm concerned about the level of air pollution in cities certainly, and I would wholeheartedly support efforts to reduce the level of air pollution in the cities for example. That can really only come from governments and local councils implementing policies that will reduce this level of air pollution for example in urban environments. But these things are at least possible. If not, easy.
Kat - That was Professor David Phillips, from Kings College London.