Scientists find genetic link between immune system and lymphoma

Scientists at The Institute of Cancer Research, London, identified six new genetic changes that increase the risk of developing Hodgkin lymphoma – one of the most common cancers in young adults.

Many of the DNA changes seemed to affect the function of the immune system – three of which had previously been associated with autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis and lupus. 

Link offers better understanding

The researchers stressed that the link did not mean people with autoimmune diseases risk developing lymphoma, but did offer important genetic clues for understanding both lymphoma and autoimmune diseases better.

One of the genetic changes discovered increases the risk of Hodgkin lymphoma by more than a third and others by at least 15 per cent each – information that could guide potential new targeted drugs for the disease.

The study was funded by a wide range of organisations, including Bloodwise, Cancer Research UK and the Lymphoma Research Trust.

Scientists at The Institute of Cancer Research (ICR) analysed genetic data from 5,314 cases of Hodgkin lymphoma and 16,749 controls, from four different European studies.

The study represents the largest of its kind for the disease. In most instances, Hodgkin lymphoma can be successfully treated with first-line therapies – however, there is a need for new treatments in cases where first line treatment has failed.

Researchers identified six new single-letter changes in DNA that were linked to the development of the cancer – five of which affect the way a type of white blood cell, called B cells, develop.

Hodgkin lymphoma is a cancer of the B cells, which are responsible for producing antibodies as a critical component of the immune system. 

Identifying specific risk to lymphoma

The study also pinpointed clear differences in genetic risk between two different subtypes of the disease – nodular sclerosis Hodgkin Lymphoma (NSHL) and mixed cellularity Hodgkin Lymphoma (MCHL).

For example, a single-letter change located in DNA near the gene LPP increased the risk of NSHL by 37 per cent, but had little effect on the risk of developing MCHL. 

Commenting on the ramifications of the findings, Professor Richard Houlston, Professor of Molecular and Population Genetics at The Institute of Cancer Research, London, said: “Hodgkin lymphoma is a cancer of immune cells called B cells, and our study links the risk of the disease to changes in the genes that control how B cells develop.

“Interestingly, we found that some of the genetic changes we have linked to Hodgkin lymphoma have previously been associated with the risk of autoimmune diseases such as multiple sclerosis and rheumatoid arthritis.

Professor Paul Workman, Chief Executive of The Institute of Cancer Research, London, said: “Understanding the genetic changes that underpin cancer’s development is crucial for all aspects of our quest to defeat cancer – to understand which patients are most at risk from different types of cancer, to improve diagnosis, and to develop treatments that are most likely to work for individual patients.

“This important new study sheds light on the DNA changes that can contribute to a person’s risk of developing Hodgkin lymphoma, and offers clues as to how they might increase that risk, including the interesting link to the immune system. These findings could lead to new ways of managing the disease.”

Dr Alasdair Rankin, Director of Research at Bloodwise added: “Because of research, treatments for many people with Hodgkin lymphoma are now good, and around 80 per cent of all people affected survive in the long term. Although this is good news, treatments can have long-term health effects, such as infertility and secondary cancers, so finding kinder treatments for Hodgkin lymphoma is important. We welcome this study, which sheds new light on how Hodgkin lymphoma develops.”