11:28pm Friday 03 July 2020

Mutations link common immune condition with blood cancer

A team at The Institute of Cancer Research, London, found that a common group of genetic variations appeared to increase the risk of developing both myeloma and a condition called monoclonal gammopathy of undetermined significance (MGUS).

Seven genetic mutations associated with myeloma also appeared to influence the risk of a person developing MGUS.

MGUS isn’t harmful and has no symptoms but each year, 1% of MGUS patients develop multiple myeloma. Relatives of individuals with MGUS also have a higher than normal risk of multiple myeloma, suggesting that the two conditions have a hereditary element.

The new findings could help to identify which people with the condition are likely to go on to develop myeloma

The study, published in the journal Blood, was funded by Myeloma UK, Leukaemia and Lymphoma Research and Cancer Research UK, with additional funding from the NIHR Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research (ICR).

 MGUS is a condition where plasma cells in the blood produce too much of a particular antibody called a paraprotein. The condition is fairly common, affecting 2% of people over 50, with approximately 3,800 patients diagnosed every year in the UK.

Previous research has shown that genetic mutations found at seven regions of DNA increase a person’s risk of developing multiple myeloma but it hadn’t been known if they were also linked to MGUS.

Scientists at the ICR examined the DNA of 492 patients with MGUS and 7,306 controls, to determine if mutations which increase the risk of developing multiple myeloma also affect MGUS patients.

The researchers saw that each mutation was associated with increasing the risk of a patient developing MGUS, which was statistically significant for four of the mutations. They also found that patients with more of these mutations had a higher risk of developing MGUS than patients with fewer mutations.

These results suggest that the genetic variation influencing a patient’s risk of developing multiple myeloma forms through a predisposition to MGUS.

Professor Richard Houlston, Professor of Molecular and Population Genetics at the ICR, said: “We know that families of patients with MGUS have a greater chance of developing myeloma but this research helps to confirm that there is a genetic link between the two conditions. The seven genetic variations associated with multiple myeloma also increase a person’s risk of having MGUS, and the more of these mutations they have, the greater their risk.

“Blood tests can indicate if someone has MGUS, but at the moment they don’t predict who will go on to develop multiple myeloma. Our study’s findings could be used to develop a genetic test that could help doctors identify which MGUS patients are at the greatest risk of going on to develop cancer.”

The Institute of Cancer Research, London


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