Monday August 17 2009
White blood cells from a patient with ALL, a type of leukaemia
A study has found particular gene mutations that put children at a higher risk of leukaemia, newspapers have reported. The Times's article on childhood leukaemia genes said that “research into the development of acute lymphoblastic leukaemia (ALL)… suggests that individuals who inherit specific genetic variants are almost twice as likely to develop the disease”.
Acute lymphoblastic leukaemia (ALL) is the most common leukaemia in children, and accounts for a quarter of all childhood cancers. This genome-wide association study identified three gene variations that are more common in children with ALL than in those without it.
The study is well-conducted, and its results significantly advance our knowledge of this condition. However, ALL is a complex disease and is likely to have many causes, some genetic and some environmental. These findings do not mean that researchers know how to prevent the disease in children found to have these mutations. Also, the variants discovered in this study will not be responsible for all cases of leukaemia. At the present time, genetic testing of children for these mutations is unlikely.
Where did the story come from?
The research into childhood leukaemia genes was carried out by Dr Elli Papaemmanuil and colleagues from the Institute of Cancer Research in Surrey, and other academic and research institutes in the UK. It was funded by Leukaemia Research (UK) and the Kay Kendall Leukaemia Fund. The authors also acknowledge funding from Cancer Research UK. The study was published in the peer-reviewed medical journal Nature Genetics.
What kind of scientific study was this?
Acute Lymphoblastic Leukaemia (ALL) is the most prevalent childhood cancer in developed countries. Although its exact cause is not known, factors such as radiation exposure, some genetic disorders and the environment (exposure to certain chemicals and some infections) increase the risk of a child developing ALL.
This genome-wide association study looked for particular gene sequences (variants) associated with leukaemia in children. By pooling the results of two case-control studies, a total of 907 children with leukaemia and 2,398 controls without leukaemia were available for analysis. These children’s gene sequences were compared in order to test for variations that were more common in the children with leukaemia. Only people of western European ancestry were included.
Between the groups, 291,423 gene variants were examined and compared. Where significant links were found between variants and disease status, the researchers discuss other studies that may explain the biological reasons for these associations. In one case, they investigated this further through experimentation.
What were the results of the study?
The researchers found that three gene variants in their pooled sample were more common in leukaemia cases than in controls. One variant was found on a gene called IKZF1, one on a gene called ARID5B, and one on a gene called CEBPE. All three of these variants were in genes involved in the differentiation (specialisation) of certain types of white blood cells.
What interpretations did the researchers draw from these results?
The researchers say that their study provides the first unambiguous evidence that common gene variants influence the risk of developing ALL in children. They say that their results provide ‘new insight’ into the causes of this specific haematological cancer.
What does the NHS Knowledge Service make of this study?
This is a well-conducted study and the results are reliable. It identified several gene variants that are more common in children with acute lymphoblastic leukaemia (ALL). There may be other genes that play a role in the condition:
- The researchers acknowledge that the risk of ALL may be affected by ethnic differences. As this research was limited to western European children, the findings may not apply to non-western Europeans or non-Europeans.
- The knowledge that certain variants are associated with leukaemia does not mean that researchers know how to prevent the disease in children with the variations. Leukaemia is a complex disease, and the risk of developing it is likely to be linked not only to genes, but also to environmental factors. In addition, not all cases of leukaemia may have these variations.
- More research is needed before we know whether the proteins that are encoded by these genes are suitable targets for leukaemia treatments.
Overall, this study advances our knowledge of a complex disease. The findings are robust, but replication in further studies using different cases and controls would increase the confidence that the associations found in this research are real.
Links to the headlines
Research links childhood leukaemia to parents’ genes. The Times, August 17 2009
Child leukaemia 'genes' revealed. BBC News, August 17 2009
Genes 'could play significant role in development of leukaemia'. The Daily Telegraph, August 17 2009
Links to the science
Papaemmanuil E, Hosking FJ, Vijayakrishnan J, et al. Loci on 7p12.2, 10q21.2 and 14q11.2 are associated with risk of childhood acute lymphoblastic leukemia. Nature Genetics 2009; Published online: August 9
Cochrane: Several reviews deal with issues relating to the treatment of ALL; none address causes specifically:
van Dalen EC, Raphaël MF, Caron HN, Kremer LCM. Treatment including anthracyclines versus treatment not including anthracyclines for childhood cancer. Cochrane Database of Systematic Reviews 2009, Issue 1
Sasse EC, Sasse AD, Brandalise SR, Clark OAC, Richards S. Colony-stimulating factors for prevention of myelosuppressive therapy-induced febrile neutropenia in children with acute lymphoblastic leukaemia. Cochrane Database of Systematic Reviews 2005, Issue 3