Scientists have found four new regions of the genome that increase the risk of a common blood cancer, according to results published in the journal Nature Genetics.

Professor Richard Houlston and his team at The Institute of Cancer Research (ICR) have now found the location of 10 genetic variants, common in the European population, that are associated with an increased risk of chronic lymphocytic leukaemia (CLL).

Professor Houlston's team last year proved that people's genes could make them more susceptible to CLL, identifying six regions of the genome more common among sufferers. In the latest paper, also funded by the charity Leukaemia Research, his team have identified another four regions that influence an individual's risk of CLL.

CLL is the most common form of leukaemia in western countries, with around 2,700 people in the UK diagnosed each year with the disease, most after age 55.

The genetic factors identified in the latest study are all common in the population, and each increases the risk of CLL by between 1.2 and 1.4-fold. Each person may carry from a few of the identified risk factors to all the risk factors. Importantly, the more genetic factors carried, the higher their risk of developing CLL.

"People who have more than 13 risk factors are seven times more likely than the general population to develop CLL," Professor Houlston says.

The risk factors were identified using a genome wide association study, a technique that ICR scientists have used previously to find risk genes in breast, prostate, testis, brain and colon cancer and childhood leukaemia. They scanned the genome of 2,503 CLL patients and compared them to 5,789 healthy individuals, looking for single letter differences in DNA between the two groups.

The study confirmed that the inherited risk of CLL is not due to a single gene, but often as a result of the cumulative effect of many genetic changes with small effects. The study found that 87 per cent of people with CLL would have at least one of these genetic factors.

The locations of these factors also provides new insights into the mechanism by which leukaemia develops.

Dr David Grant, Scientific Director of Leukaemia Research, says, "The possibility that this form of leukaemia may run in families has been suspected for sometime. So it is pleasing that this research is providing the genetic evidence that an increased risk of developing CLL can be inherited. However it is clearly a complex picture and we need to study more families before we can be certain of the particular genetic traits that are most important."

Notes

- The present study found risk factors at chromosome positions 2q37.7, 8q24.21, 15q21.3 and 16q24.1. It also found weaker evidence for another two risk factors at positions 15q25.2 and 18q21.1.

- The previous study found risk factors at positions 2q13, 2q37.1, 6p25.3, 11q24.1, 15q23 and 19q13.32.

Source
The Institute of Cancer Research (ICR)
Leukaemia Research

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