Wednesday 23 April 2003
Scientists at The Institute of Cancer Research, as part of the UK Childhood Cancer Study (UKCCS) (1) have shown that there may be a link between levels of folic acid available to the baby in the womb and leukaemia in children.
Women are already advised to take supplements of folic acid while trying to conceive and throughout pregnancy to help avoid the risk to the foetus of brain damage and spina bifida. Deficiency of folic acid is known to lead to breaks in DNA, and low dietary intake of folic acid has been associated with increased risk of some cancers in adults, including colon and breast cancer.
This latest research, funded by the Leukaemia Research Fund and led by Professor Mel Greaves at The Institute of Cancer Research, suggests that children exposed to higher levels of folic acid in the womb have a significantly lower risk of developing leukaemia.
The scientists examined British children diagnosed with leukaemia from 1992 until 1998 and compared them with healthy children.
Professor Greaves of The Institute of Cancer Research says “We know that many cases of childhood cancer are initiated before birth by chromosome damage, so we wanted to find out if folic acid levels in cells in the developing foetus might influence risk. The active levels of folate in the cell are determined both by dietary intake, via the pregnant mother, and by genetic variations that determine how individuals process folate.”
One of the key enzymes central to the processing of folic acid, breaking it down and reducing its levels, is called MTHFR. Some individuals inherit a variant MTHFR gene - c677T, which renders MTHFR inactive and so preserves higher levels of folic acid in cells for maintaining intact DNA. Children who had inherited the inactive enzyme were found to have a significantly lower risk of leukaemia, which is presumed to be due to a reduced likelihood of chromosome damage in the womb.
The credibility of this explanation is endorsed by a recent epidemiological study carried out at the Cancer Foundation of Western Australia. Researchers there found that there was a link between the dietary intake of folic acid during pregnancy and childhood leukaemia.
The Australian scientists studied 98 children who were diagnosed with leukaemia between 1984 and 1992, and compared them with 166 children of the same age without leukaemia. Both parents were questioned about their backgrounds, lifestyles, occupations and exposures, medical histories and medication. The scientists found that use of folic acid during pregnancy almost halved the risk to children of developing leukaemia.
Other exposures after birth including infections are thought to be critical to the development of childhood leukaemia, but this new result suggests that folic acid in diet and inherited factors regulating folate levels in the body are also important pre-natal risk factors for childhood leukaemia, just as they appear to be for several adult cancers.
Dr David Grant, Leukaemia Research Fund Scientific Director, says “About one in 2,000 children will be diagnosed with leukaemia, most between two and four years of age. Professor Greaves’ painstaking detective work at The Institute of Cancer Research is showing that some of these children are almost certainly born with defective blood cells which go on to become leukaemic cells. The realisation that damage to the DNA in these cells can be reduced with folate supplements in pregnancy is extremely exciting and could help to reduce the number of cases of this terrible disease in children. This is a very interesting lead and we look forward to the results of further studies.”
Meanwhile, Professor Greaves’ work goes on to identify possible post-natal triggers that may force abnormal blood cells to become leukaemic.
Professor Peter Rigby, Chief Executive of The Institute of Cancer Research says “This research has given us a clearer understanding of the role of folic acid. We hope that further research will shed more light on this in relation to childhood cancer, and provide the evidence that is needed for a more radical health policy, and longer term to a reduction in childhood cancers.”
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For further information, or to arrange interviews, please contact:
Marie MacLean
Press Officer
Institute of Cancer Research
Tel: 020 7153 5359
Email: [email protected]
Notes to editors
- This study was carried out as part of the UK Childhood Cancer Study (UKCCS).The UKCCS was sponsored and administered by the United Kingdom Co-ordinating Committee on Cancer Research (UKCCCR) and was supported by the UKCCS paediatric oncologists and by the National Radiological Protection Board. Financial support was provided by: Cancer Research UK, Leukaemia Research Fund and Medical Research Council through their grants to their units; Department of Health; member companies of the Electricity Association, Irish Electricity Supply Board, National Grid Company plc and Westlakes (Trading) Ltd for general expenses of the study; Kay Kendall Leukaemia Fund for associated laboratory studies and Foundation for Children with Leukaemia for study of electrical fields. The investigation in Scotland is funded by the Scottish Office, Scottish Power plc, Scottish Hydro-Electric plc and Scottish Nuclear Ltd.
- The Australian study was funded and led by the Cancer Foundation of Western Australia
- The Institute of Cancer Research is one of the world's leading cancer research organisations and is internationally renowned for the quality of its science. Its mission is the relief of human suffering by pursuing excellence in the fight against cancer. The Institute is an Associate Institution of the University of London. The Institute works in a unique partnership with The Royal Marsden Hospital and together they form Europe’s largest comprehensive cancer centre.
- References:
Wiemels JL, Smith RN, Taylor GM, Eden OB, Alexander FE, Greaves MF, UK Childhood Cancer Study Investigators (2001) Methylenetetrahydrofolate reductase (MTHFR) polymorphisms and risk of molecularly defined subtypes of childhood acute leukemia. Proc Natl Acad Sci USA, 98: 4004-4009.
Thompson JR, FitzGerald P, Willoughby MLN, Armstrong BK (2001) Maternal folate supplementation in pregnancy and protection against acute lymphoblastic leukaemia in childhood: a case-control study. Lancet, 358: 1935-1940.
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