The majority of childhood leukemias probably arise as a consequence of an abnormal immunological response to one or more common infections. '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.'

Major sign-posts along the pathways leading to childhood leukemia have been identified in the largest and most comprehensive investigation of childhood leukemia and other cancers ever undertaken anywhere in the world -- the United Kingdom Childhood Cancer Study (UKCCS) -- which was conducted over a 15-year period.

Early Infection Exposure Is Necessary

New data presented at a conference earlier in the week confirmed that the majority of childhood leukemias 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 -- including attendance at play groups or day care -- appear to have lower rates of leukemia.

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 leukemia and perhaps other diseases of childhood common in affluent societies.

Challenge to the Immune System

Researchers conducting the UKCCS interviewed parents and collated biological material and clinical records of 3,838 children diagnosed with cancer, including 1,737 with leukemia. A comparison group of an additional 7,629 children without cancer also was studied.

In addition to looking at immunological pathways, the researchers investigated exposures to various environmental conditions, including household levels of background radiation (ionizing and electromagnetic), parental smoking and occupation, breastfeeding and neonatal vitamin K administration. They also considered a wide range of factors occurring during pregnancy and shortly after birth.

"Understanding causation, and thereby finding ways to prevent childhood leukemia, is a key objective for the Leukaemia Research Fund," said Sir Walter Bodmer FRS, Chairman of the LRF Medical & Scientific Advisory Panel.

"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 leukemia remains a puzzle to be solved, as is the role of inherited susceptibility," he added.

Exposure to Radiation, Electromagnetic Fields

"Analysis of the huge amount of data collected from over 1,500 families who had a child diagnosed with leukemia during the course of the study is still ongoing," noted Professor Mel Greaves FRS, Head of the Section of Haemato-Oncology, the Institute of Cancer Research, referring to the UKCCS.

"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 leukemia in children," he said.

"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 favoring the outgrowth of blood cells which have been carrying a chromosomal/genetic lesion acquired before birth during fetal 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," Professor Greaves observed.

Day Care Attendance

A study similar to the UKCCS model currently is underway in California.

"The Northern California Childhood Leukemia Study has investigated delayed social contact in day care and the risk of childhood leukemia using comparable methods to UKCCS," said Professor Pat Buffler, School of Public Health, University of California Berkeley.

"The study has shown a highly significant relationship of a lower leukemia 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 leukemia 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 leukemia we now have the biological and epidemiological foundations to begin a consideration of preventive measures," Professor Buffler concluded.