Scientists at The Institute of Cancer Research (ICR) in London have identified a heritable gene variant associated with an increased risk of developing chronic lymphocytic leukaemia (CLL).
CLL is the most common form of leukaemia in Western countries, with around 3,300 people in the UK diagnosed with the disease every year. For some time it has been known that the risk of developing CLL is increased in certain families, but the genetic basis for inherited predisposition to CLL is only just coming to light.
Recent studies by the ICR team have shown that while there is no single ‘cancer gene’ for CLL, susceptibility can be explained by the co-inheritance of multiple risk variants that increase risk when inherited in combination.
Ultimately, the scientists, who were funded by Leukaemia & Lymphoma Research, hope that increasing our understanding of the inheritable genetic factors driving cancer development may help us discover new drugs or develop screening programmes that target high-risk individuals.
In a new study published in the journal Blood, the ICR team identified another key region of the genome linked to inheritance of CLL.
Studies that look for new genetic associations with diseases are known as genome wide association studies (GWAS). The scientists combined data generated by three GWAS independent studies in what is called a ‘meta-analysis’. This allowed the analysis of genetic information from 1,121 leukaemia patients and 3,745 healthy controls. As a result a new CLL ‘risk’ inherited variant was identified positioned at a very specific point on a single chromosome encoded as 6p21.33.
Study leader Professor Richard Houlston, leader of the molecular and population genetics team at The Institute of Cancer Research, said: “We investigated the combined effect of this newly found risk variation and other known CLL related variants. There was no evidence of interaction between the genes, indicating that each locus plays an independent role in increasing risk.
“These gene variations contribute significantly to the development of CLL. While risks associated with each variant are individually modest, these variations are frequently carried by individuals of European ancestry. This variant is the thirteenth that we have discovered – so while each one alone has a small effect on the risk of developing CLL, in combination these risks are important. The genetic variants we have found so far account for around 16 per cent of the inherited risk of CLL, so we believe there are more genetic variants still to be found.”
The researchers established that a strong relationship exists between the ‘risk’ locus positioned at 6p21.33 and reduced expression of the BAK1 gene found at that location. BAK1 plays a key role in the maintenance of levels of healthy immune cells, called B cells, in the blood. Deficiency in BAK1 was observed to inhibit natural cell death, leading to an accumulation of immature and mature B cells. This finding provides a fascinating insight into the biological basis of how CLL develops.
Professor Chris Bunce, Research Director of Leukaemia & Lymphoma Research, said: “This study offers more compelling evidence for the role of inheritable risk genes in hijacking the natural cell cycle. More research is needed to establish just how significant this newly discovered risk gene variant is in the development of CLL.”
Find out more about our research into CLL at our Research Open Day in Cardiff coming this coming October.