Pathways leading to childhood leukaemia identified

Blood
Pathways leading to childhood leukaemia identified
By Leukaemia Research, UK, Apr 25, 2005 - 7:31:38 PM

The leading UK leukaemia research charity (LRF) reveals today (Friday) that major sign-posts along the pathways leading to childhood leukaemia have been identified.

The findings come from the largest and most comprehensive investigation of childhood leukaemia and other cancers ever undertaken anywhere in the world The United Kingdom Childhood Cancer Study (UKCCS)1.

At a meeting earlier this week to examine the results of this 15-year study, world experts discussed the possible causes of childhood leukaemia. They confirmed that most childhood leukaemias have their origins before birth, but that later infectious events in infancy and childhood may trigger an abnormal immune response leading to disease. They further agreed that the timing of exposure to common infections in infancy and later in childhood was critically important.

This unique project interviewed parents, and collated biological material and clinical records of 3,838 children diagnosed with cancer, including 1737 with leukaemia. A comparison group of further 7,629 children without cancer was also studied.

As well as looking at immunological pathways, other exposures evaluated included household levels of background radiation (ionising and electromagnetic), parental smoking and occupation, breast-feeding and neonatal vitamin K administration, as well as a wide range of factors occurring during pregnancy and shortly after birth.

Chairman of the LRF Medical & Scientific Advisory Panel Sir Walter Bodmer FRS comments: "Understanding causation and thereby finding ways to prevent childhood leukaemia is a key objective for the Leukaemia Research Fund. Our investment of several million pounds in the 15-year UKCCS project has been rewarded with a much clearer idea of why, when and how children get leukaemia.

"The most plausible explanation now seems to be a challenge to the child's immune system, quite possibly involving common infections, which cause the cancerous blood cells to emerge. How such a challenge triggers leukaemia remains a puzzle to be solved, as is the role of inherited susceptibility."

Professor Mel Greaves FRS, Head of the Section of Haemato-Oncology, The Institute of Cancer Research, comments: "The UKCCS project has been the most exhaustive and detailed study ever conducted into identifying possible causes of leukaemia in children.

"Analysis of the huge amount of data collected from over 1,500 families who had a child diagnosed with leukaemia during the course of the study is still ongoing.

"However, it is clear that perceived risk factors such as living near sources of electromagnetic fields or natural radiation like radon are not principal causes, if at all, of leukaemia in children.

"The epidemiological evidence fits with the known biology of the disease and points to an abnormal response in a child's immune system to infection favouring the outgrowth of blood cells which have been carrying a chromosomal/genetic lesion acquired before birth during foetal development. The timing or pattern of infections very early in life appears to be critical as is, most probably, the genetic background of the individual at risk."

New data presented at the conference confirmed that the majority of childhood leukaemias probably arise as a consequence of an abnormal immunological response to one or more common infections. Furthermore, children with a wide range of social contacts outside the home during infancy appear to have lower rates of leukaemia.

Exposure to infections in the first months and years of life is known to be necessary for normal immune system development, and scientists believe that children who are not exposed may be more likely than those who are to develop leukaemia and perhaps other common diseases of childhood in affluent societies.

A study similar to the UKCCS model is currently underway in California. Professor Pat Buffler, School of Public Health, University of California Berkeley comments: "The Northern California Childhood Leukemia Study has investigated delayed social contact in day care and the risk of childhood leukaemia using comparable methods to UKCCS.

"The study has shown a highly significant relationship of a lower leukaemia risk with higher child hours of exposure to infectious agents as estimated from day care attendance. There is still much to learn about the mechanisms underlying this immune response and the association with leukaemia risk as well as the role of other environmental exposures and genetic susceptibility.

"For the first time in the long history of research into the causes of childhood leukaemia we now have the biological and epidemiological foundations to begin a consideration of preventive measures."

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