Scientists identify genetic variations that affect childhood leukaemia risk

In collaboration with the Press Association

Two new studies, including one by scientists at the UK's Institute of Cancer Research (ICR), have uncovered a number of inherited genetic variations that increase children's risk of developing acute lymphoblastic leukaemia (ALL), the most common form of cancer in children.

Scientists at the ICR previously identified mutations linked to ALL that occur during development in the womb, as well as other changes that occur after birth.

But this is the first time inherited risk factors have been identified, although the researchers noted that ALL does not appear to run in families.

 

The studies, which both appear in the journal Nature Genetics, were possible thanks to new technologies that allow the entire genetic makeup of ALL patients to be compared against healthy people so that any differences can be identified.

In their study, UK scientists found differences in three genes - IKZF1, ARID5B and CEBPE - each of which individually increased the likelihood of its carrier developing ALL by between 30 and 60 per cent.

The genes have been implicated in the development of white blood cells called lymphocytes, which are altered in ALL.

Professor Richard Houlston, head of the ICR's Molecular and Population Genetic Team and a Cancer Research UK grantee, said: "These findings provide the first evidence that genetic makeup plays a major role in the risk of ALL and insight into how the disease develops."

Co-investigator Professor Mel Greaves, chairman of the ICR's Section of Haemato-Oncology, added: "This is a very significant advance in our understanding of the complex process by which children develop leukaemia.

"The new results should not be taken, by parents or the public at large, to mean that children develop leukaemia because of an accident of inheritance. Genetic risk factors are just one component of cause.

"Finding the triggering exposures still remains a focus of intense effort, particularly with respect to possible future prevention."

In the second study, which was carried out by researchers at St Jude Children's Research Hospital in the US, 18 separate genetic variations were identified - two of which occurred in one of the genes arising from the UK study - ARID5B - and one in another - IKZF1.

The US scientists estimate that these two genes were involved in just over a third of ALL cases and note that one of them may help to predict an individual's response to treatment.

Senior author Dr Mary Relling, pharmaceutical sciences chair at St Jude, explained that the same inherited variation in ARID5B also affects the effectiveness of chemotherapy drug methotrexate in leukaemia cells.

"It accumulates better," she revealed. "That allows us to use a lower dose and still cure the leukaemia.

"These findings may identify a new marker that could be used to help decide on doses of methotrexate in patients with varying ARID5B status."

Oliver Childs, senior science information officer at Cancer Research UK, commented: "Scientists still don't know what causes most cases of leukaemia, but this fascinating work shows how a child's genes can help influence their risk of developing the disease.

"Large-scale genetic research like this opens up many interesting scientific avenues to explore. The challenge ahead for Cancer Research UK and other organisations is to apply this new genetic knowledge to help gain further insights into this type of leukaemia."