Three genetic variants linked to common childhood leukemia found


Three genetic variants linked to common childhood leukemia found

UK scientists have for the first time found three genetic variants that raise children's risk of developing acute lymphoblastic leukaemia (ALL), the most common childhood cancer. The discovery should help us to understand more about how ALL develops, they said.

Scientists from the Institute of Cancer Research (ICR) found the three variants by comparing the DNA of heatlhy patients to patients with ALL. They write about their research in this week's Nature Genetics, dated 16 August.

Lead geneticist on the study, Professor Richard Houlston, who heads ICR's Molecular and Population Genetics Team, told the press that:

"These findings provide the first evidence that genetic makeup plays a major role in the risk of ALL and insight into how the disease develops."

In the UK, about 400 children are diagnosed with ALL each year, making it the most common type of childhood cancer.

In healthy people white blood cells grow and divide in an orderly fashion, with a controlled balance between new and immature cells and mature cells that work to stop our bodies being overwhelmed by bacteria, viruses and other undesirable agents that make us sick.

But leukaemia upsets the balance by making cells divide before they are ready and so they don't mature. If they don't mature, they clog up the bone marrow and stops it making blood cells properly, and eventually this impairs the immune system and leads to increased risk of infection and disease.

Acute lymphoblastic leukaemia (ALL) is where there are too many immature lymphoblast white blood cells, also known as blast cells, of which there are two types: B-lymphocytes and T-lymphocytes.

Scientists now believe there are three things that come together to trigger cancer: something in our environment, something we inherit from our biological parents, and just "chance".

Scientist from ICR had already done work to suggest that a blood cell mutation that is present before birth, and other mutations that occur after birth (the latter perhaps triggered by an environmental event such as a childhood infection), are involved in childhood ALL.

Although ALL does not appear to run in families, the ICR team has now discovered that inherited risk factors are probably linked to its development.

They did a genome-wide association study, a method that has already been successful with prostate, brain, colon and other cancers, where they compared the DNA of 2,398 healthy patients without ALL to 907 patients with ALL.

To examine the DNA, they scanned 291,423 single nucleotide polymorphisms (unique strips of DNA code) from each participant's genome.

They found three SNP variants were present in ALL patients but not in the healthy controls, and each variant increased the risk of ALL by 30 to 60 per cent.

The chromosome locations or loci of the SNP variants are: 7p12.2, 10q21.2 and 14q11.2, and the genes they are part of control the development of lymphocytes, the white blood cell types that are altered in ALL.

Study co-investigator professor Mel Greaves, a leukaemia biologist who chairs ICR's Section of Haemato-Oncology said:

"This is a very significant advance in our understanding the complex process by which children develop leukaemia."

However, he went on to explain that parents and the public in general should not take these results to mean that childhood leukemia develops because of "an accident of inheritance".

It is still important to find out what triggers the genetic factors, and looking for these factors in our environment "still remains a focus of intense effort, particularly with respect to possible future prevention," he said.

Dr David Grant, Scientific Director at Leukaemia Research welcomed the research and said that helping us understand more about how leukaemia develops "will lead to new, less punishing, treatments to cure all children with this cruel cancer."

The research was funded by Leukaemia Research and the Kay Kendall Leukaemia Fund.

"Loci on 7p12.2, 10q21.2 and 14q11.2 are associated with risk of childhood acute lymphoblastic leukemia."

Elli Papaemmanuil, Fay J Hosking, Jayaram Vijayakrishnan, Amy Price, Bianca Olver, Eammon Sheridan, Sally E Kinsey, Tracy Lightfoot, Eve Roman, Julie A E Irving, James M Allan, Ian P Tomlinson, Malcolm Taylor, Mel Greaves and Richard S Houlston.

Nature Genetics, 16 August 2009.

DOI:10.1038/ng.430

Sources: ICR News, cancerbackup.

Mayo Clinic-Led Researchers Confirm Gene Variants Associated With The Most Common Adult Leukemia (Video Medical And Professional 2020).

Section Issues On Medicine: Disease