Is Cancer Written into our DNA?

Increasingly, scientists are discovering a genetic component to cancer and other debilitating diseases including schizophrenia and even autism. And that raises an interesting conundrum: If natural selection, Darwin's theory of evolution, is supposed to advance traits that promote the fittest and the survival of the species, why has it not weeded out genetic conditions that kill or are so obviously anti-social?

Bernard Crespi of Simon Fraser University.

That question has not escaped the notice of evolutionary biologists such as Bernard Crespi, a research scientist at Simon Fraser University, in Burnaby, B.C., who has written extensively on the subject. He and others in this field argue that an evolutionary perspective ought to be brought to more mainstream cancer research because, among other things, cancer cells seem to have their own Darwinian impulses, may evolve from conflicts between certain maternal and paternal genes and can be fuelled by the body's own inner-workings.

Prof. Crespi spoke with CBC producer Robert Sheppard.

Are certain diseases, such as cancer, written into our DNA?

When you say "written into" that presumes a certain inevitability. Are certain diseases fundamentally genetic diseases? Yes. And cancer is certainly due to particular genetic alterations.

But when you say "written into" you may also be referring to a genetic predisposition to cancer as something that has evolved. There is certainly evidence for this as well. Probably the clearest evidence has to do with tradeoffs between cancer and senescence [aging]. These have been well documented and linked to specific genes.

How does this work?

The idea here is that if you have a cell that has undergone some mutations that aren't good for the overall system, then one thing the body can do is turn off that cell or kill that cell. If the body does that it reduces the risk of that cell becoming cancerous down the road.

But you also end up with fewer cells. And one of the primary causes of human aging is a result of the body shutting down cells that have started to go bad.

So you can either get cancer or you can get old. That's a fundamental feature of the way cells work and the way genes work.

Are there other diseases that can be seen in this light as well?

Well, certain neurodevelopmental diseases like autism and schizophrenia have a very strong genetic basis as well.

One way to think about these is that you have all these different genes that make up the various aspects of the way people think, or their behaviour or how good they are at things like math or art.

You can have a normal distribution of these traits across the general population that are underlain by genetic variation. But if you have too many alleles — or genetic variants — for being good at math or science or engineering, that can result in disorders relating to autism or autism itself. You can think of it as too much of a good thing.

In the Darwinian sense, why hasn't natural selection phased out these harmful traits?

Why hasn't natural selection gotten rid of cancer or autism or schizophrenia? Nobody really knows the answer to that for sure but there are certainly many interesting ideas.

One important cause of these conditions is the way genes work. All genes have multiple effects, that's the way they've developed over time. So if you have a gene that is good for you and has a nice positive effect, it will be selected even if it has some negative effects.

You take the good with the bad

Right, and that's one of the main theories of aging. If you have a gene that's good for you early in life, it's going to be selected for over evolutionary time even if it may have negative effects late in life.

So, sure, there is selection pressure against schizophrenia, it's a devastating disorder. But there may also be selection for having a certain number of genes that are related to the disorder. Some of the alleles associated with schizophrenia, for example, have been related to aspects of creativity.

Is there a parallel here to how cancers develop as well?

Partly, but these diseases and disorders may also flow from something we call parent-offspring conflict. It's another one of the fundamental aspects of the way that genes and evolution work.

We usually think of the mother and child as having exactly the same interests. But they are related to one another only by one half. One half of their genes is completely different. So they don't have exactly the same interest in regard to the sharing of resources during development and reproduction.

What this means is that children, from conception on, have evolved to try to take a little bit more from their parents, especially the mother, than the mother is prepared to give.

In humans you can see this clearly in the development of the placenta. It develops from the offspring and is basically a tissue that invades the mother. One of the first things that it does is move into the blood vessels on the uterine wall and it modifies these blood vessels so they cannot be constricted. Basically, it is guaranteeing that the mother cannot reduce the flow of blood.

How does this conflict encourage cancer?

Essentially what happens is that paternally expressed genes are the ones that favour taking more from the mother, while maternally expressed ones favour the mother providing less.

This genetic tug-of-war, which is a very dynamic balance, controls fetal growth and aspects of cell proliferation, often by their effect on proteins called growth factors.

Growth factors are one of the major facilitators in the development of cancer, which of course is all about cells growing uncontrollably. These are just cells that have escaped the usual controls on replicating themselves and aspire to a certain kind of immortality.

So the fact that these conflicts exist over what are called imprinted genes can result in an increased risk of cancer over time.

Variations of these genes will affect how tall you are, for example. If you have more of these growth factors, you may grow tall. But you may also have an increased risk of cancer because your cells will have an increased tendency to push toward growth.

What are the implications for research and treatment?

Well, this is a real problem in the field in a general sense. Molecular biology has become really specialized and focused on the pathways of the disease, trying to shut these down. So you have all the cancer biologists on one side and the evolutionary biologists on the other and very few people are being trained in both disciplines.

We evolutionary biologists are saying that cancer is fundamentally an evolutionary disorder. You can essentially consider cells to be like a population of organisms, struggling for survival.

The payoff in cross training in cancer and evolution is way down the road, of course. But we ought to be focusing as directly as possible on the evolutionary processes and the genetic changes that we believe are taking place, particularly on those genes involved in conflicts.

We know of about 100 imprinted genes and it is suspected that there are many times that number but relatively few people are studying them because they don't have immediate applications to, say, developing a new cancer therapy.

But in the long run, it is genes like these that run the show.