What causes cancer? If we know this then we can try to find ways to prevent it.

That’s why a review out today is important. It looks at all the evidence around a type of cancer called childhood acute lymphoblastic leukaemia (ALL), using evidence from published studies to try and pinpoint a cause.

And today in London, the scientist behind the review presented his theory, based on 30 years of work on the topic.

It’s important to say that the review only looked at childhood ALL. Because different types of cancer have different causes, these results won’t be the same for other forms of the disease.

What is ALL?

ALL is a type of blood cancer that starts in the bone marrow. It’s the most common type of leukaemia to affect children, with the highest incidence in young children aged 0 – 4 years. It can also affect adults, but can be considered a different disease.

Around 6 in 100,000 children aged 0-4 will be diagnosed with ALL each year. And around 9 in 10 of those will be cured by treatment.

This is good news, but treatment is still tough on patients and their families, and can cause long-term health issues. That’s why research looking at kinder treatment and ways to prevent this disease are so important.

“Childhood leukaemia is rare and it’s currently not known what or if there is anything that can be done to prevent it by either medical professionals or parents,” says Professor Charles Swanton, Cancer Research UK’s chief clinician.

Lots of different causes have been suggested, but many lack evidence or are implausible.

What’s today’s story?

So, Professor Mel Greaves, an expert in childhood leukaemia at The Institute of Cancer Research, London, pulled together all the evidence on causes of ALL to try to find a pattern.

Research, including looking at twins, led Greaves to propose that ALL begins following two steps:

  1. A genetic fault before birth creates susceptibility to leukaemia, but doesn’t have any other impact or symptoms. Greaves says this is surprisingly common – as many as 1 in 100 babies might have such a genetic fault.
  2. In around 1 in 100 of these cases a second genetic fault triggers ALL. Greaves’ work suggests that this second step is caused by common infections.

Both steps are needed for ALL – so children whose cells are exposed to just one of the steps won’t develop the disease. And that’s the case for most children.

“It’s important to emphasise that less than one per cent of children who have the genetic predisposition described in this review, go on to develop ALL,” says Swanton.

But the key point that Greaves presents is that ALL occurs when the second step happens in children whose immune systems haven’t been challenged early in life, and built up responses to those challenges. Exposure to some common or less serious infections or microbes might protect against this second step, and if children haven’t been exposed to them then they don’t get the protection.

Exactly which infections and microbes might protect children, and how they do this, isn’t clear. The same goes for the infections that trigger the second step on the path to the disease, but Greaves points to spikes in ALL cases shortly after spikes in seasonal and swine flu cases as a possible culprit.

Does this mean ALL is preventable?

“This research sheds light on how a form of childhood blood cancer might develop, implicating a complex combination of genetics and early exposure to germs and illness,” says Swanton.

And as Greaves says, we need to look at the bigger picture.

Having older siblings, being breastfed and being in a nursery before a child’s first birthday all seem to reduce the risk of getting ALL. And it might be that these experiences and others mean that the immune system learns to recognise more microbes and deals with them better.

“Parents are in no way to blame for this. If I’m right it’s a reflection of the way our society has moved,” says Greaves.

The way we live our lives now is much ‘cleaner’ than in the past – many diseases have been eradicated and we’re exposed to fewer microbes and infections than our grandparents. This is mostly a good thing, but it does mean that our immune systems have seen less action and can sometimes overreact to what should be harmless attacks.

This has been suggested to be behind some allergies and diseases like type 1 diabetes, and it’s what Greaves is suggesting is behind the second ALL step.

In theory this means that ALL might be preventable. But in practice this is incredibly difficult, especially when it’s not clear which microbes might help or harm, and how.

Should we be screening for the first pre-ALL gene fault?

Greaves says no.

Because the first genetic fault, or mutation, is quite common and doesn’t mean that ALL will develop, he says any screening test wouldn’t give a clear enough answer.

That means overdiagnosis would be an issue, and would give needless stress to families and be a huge logistical challenge.

What now?

Greaves says that this is the best theory for most ALL cases. But he’ll be doing more research to see if it holds up.

The next step will be to try to prevent the disease in mice that are engineered to carry similar triggers to childhood ALL.

Until then, parents shouldn’t be worried that they have or haven’t done something that led to a child’s ALL.

“If their child has an accidental mutation in the womb that’s nobody’s fault,” says Greaves.

Swanton agrees: “There’s nothing that we know of that could have been done to prevent their illness.”


Greaves, M. (2018) A causal mechanism for childhood acute lymphoblastic leukaemia. Nature Reviews Cancer