DNA errors studied before they cause cancer Researchers map DNA errors that can lead to leukemia

Forty percent of all people over 60 have one or more errors in the DNA of their blood cells that are associated with leukemia. Yet very few actually develop the disease. In the current edition of Cancer Cell, researchers from the Radboud university medical center, UMCG and IKNL show exactly which errors or combinations of errors increase the risk of cancer.

When an error accidentally occurs in the DNA of a blood cell, this cell can grow and divide faster than other blood cells. Dividing faster is also a property of tumor cells. Yet such blood cells with an error do not progress directly to cancer. Indeed, it now appears that blood cells with errors associated with leukemia are common in people who have no symptoms at all: in forty percent of people over 60.

A team of researchers, including Joop Jansen and Aniek de Graaf of the Radboudumc, and Gerwin Huls and Isabelle van Zeventer of the UMC Groningen, wanted to know what makes blood cells with errors turn into tumor cells. This was not yet known. For their study, they analyzed DNA of more than 7,000 blood samples from 3359 people older than 60 years from the Groningen Lifelines cohort. From each participant two or three samples were available, almost four years apart, so the researchers could follow the development of blood cells with errors.

Effects

The study shows that the presence of groups of cells with errors increases the risk of leukemia. These cells are also a risk factor for inflammatory diseases common with aging, such as cardiovascular disease and COPD. The researchers show exactly which DNA errors lead to the fastest growth of blood cells and the highest risk of blood cancer, such as a mistake in the gene JAK2. Moreover, they show that the combination of DNA errors with a blood abnormality, such as anemia, increases the risk of cancer even further.

Much more information was known for all people who participated in the study. For example, whether they smoke, how much alcohol they drink, what medications they take and what work they do. The researchers found no correlation between the increase in blood cells with errors in DNA, and factors known to increase the risk of cancer, such as smoking, alcohol intake and obesity.

According to laboratory specialist Aniek de Graaf, at this time it is not useful to start screening all people over 60 for errors in their blood cells. 'In our opinion, that makes little sense if you are healthy. After all, there is nothing you can do about those errors. We see no correlation with risk factors, such as smoking. In addition, errors increase the chance of leukemia, but that chance is still very small. Only when you experience symptoms and visit a doctor blood analysis is important, because then it may have consequences for monitoring or treatment.'

Now that it is known which specific groups are at very high risk, a first step towards prevention has been taken. Professor of Experimental Hematology Joop Jansen: 'With our follow-up research, we are looking further into genetic and environmental factors that influence the development of leukemia, especially in those at high risk.'

About the publication

This research was published in Cancer Cell: Evolutionary landscape of clonal hematopoiesis in 3359 individuals from the general population. Isabelle van Zeventer, Aniek de Graaf, Jonas Salzbrunn, Ilja Nolte, Priscilla Kamphuis, Avinash Dinmohamed, Bert van der Reijden, Jan Jacob Schuringa, Joop Jansen, Gerwin Huls.

• Want to know more about these subjects? Click on the buttons below for more news.

  News homepage news & media