A review of more than 30 years of research suggests that the most common form of childhood leukaemia is caused by a three-step process involving two genetic mutations and lack of infection during infancy.
The review, written by Professor Mel Greaves, director of the Centre for Evolution and Cancer at the Institute of Cancer Research, London, appeared in Nature Reviews Cancer, drawing on research into the genetic, immunological and epidemiological causes of acute lymphoblastic leukaemia (ALL).
'The research strongly suggests that ALL has a clear biological cause and is triggered by a variety of infections in predisposed children whose immune systems have not been properly primed,' said Professor Greaves.
One of the mutations linked to ALL is relatively common, with one in 20 children being born with it. However, if the child's immune system is exposed to infections in infancy, it will usually work healthily and the child will be unlikely to develop ALL. However, a lack of infection in early years can lead to an immune system malfunction. In this case, when an infection occurs later in childhood, it can trigger a second mutation and ALL.
Studies in identical twins have supported this finding. While the first mutation is shared by the twins at birth, ALL only develops after the second is acquired in childhood. Further studies in mice have shown that those with a predisposing mutation are much more likely to develop ALL if they spend their early years in a germ-free environment and are later transferred to a normal environment.
Epidemiological research also falls in line with this hypothesis, particularly a case in Milan where seven children developed ALL after a swine flu outbreak. Studies have also found that children with greater exposure to microbes – through breast-feeding, vaginal birth or exposure to other children through daycare or having older siblings – are less likely to develop ALL.
Cases of ALL are increasing at a rate of about one percent a year worldwide, with the most rapid increases in developed nations. Professor Greaves suggests that the condition might be at least partly preventable.
'This still needs further investigation and any exposure of young children to infection has to be balanced with the risk of the infection,' said Dr Donna Lancaster, an oncologist at The Royal Marsden NHS Foundation Trust, who was not involved in the review. 'In the future, there may be ways to develop an immunisation which mimics this process in order to prevent leukaemia from developing.'
This form of leukaemia affects about one in 2000 children. About 90 percent of patients recover from this form of cancer, the experience remains traumatic and long-term effects of chemotherapy might influence the patient's life.