A genetic variant previously shown to be a risk factor for multiple sclerosis (MS) has been linked to a type of cancer called Hodgkin lymphoma - suggesting a common mechanism could be at work in the two diseases.

Scientists at The Institute of Cancer Research, London, analysed the DNA of almost 12,000 people and found two new genetic variants that increase the risk of Hodgkin lymphoma. Both new variants are involved in development of the immune system, potentially giving clues to the role of immunity in cancer.

The study, published today (Tuesday) in Nature Communications, was funded by Leukaemia and Lymphoma Research, with additional funding from Cancer Research UK and the Lymphoma Research Trust.

The team found the new markers by comparing the genetic make-up of 3,489 patients with Hodgkin lymphoma and 8,270 people without the disease.

An initial screen found 27 single nucleotide polymorphisms (SNPs), or single letter variations in DNA, which were candidates to increase the risk of Hodgkin lymphoma. From these 27 SNPs, researchers honed in on two, found at the chromosomal locations 3p24.1 and 6q23.3, which had a statistically significant influence on a person’s risk of developing Hodgkin lymphoma.

This finding increases the number of genetic variants known to be risk factors for Hodgkin lymphoma from three to five.

Researchers found the variation at chromosome 3p24.1 was linked to a gene known as EOMES that helps develop cell-mediated immunity, and is also a known risk factor for MS. This might explain why cases of Hodgkin lymphoma and MS are found to cluster together in families.

Some 1,900 cases of Hodgkin lymphoma are diagnosed in the UK each year. Half of cases of Hodgkin lymphoma are linked to people who have previously contracted Epstein-Barr virus (EBV), the viral infection that causes glandular fever. However, research from The Institute of Cancer Research (ICR) and others has shown an increasing role for genetic factors.

Professor Richard Houlston, Professor of Molecular and Population Genetics at The Institute of Cancer Research, said:

“Our study found for the first time that a genetic variant known to be a risk factor for multiple sclerosis is linked to Hodgkin lymphoma, showing that the two diseases might share a common mechanism. The risk factor is linked to a gene called EOMES, which is important for the immune response, providing new insights into the biological basis of Hodgkin lymphoma.

“Although many people are aware of the link between Hodgkin lymphoma and the glandular fever virus, we are also uncovering more and more evidence of the genetic nature of the disease. This study builds on our previous seminal work and brings the number of genetic variants known to be risk factors for Hodgkin lymphoma to five.”

Professor Alan Ashworth, Chief Executive of The Institute of Cancer Research, said: 

“Our immune systems must strike a fine balance between on the one hand remaining vigilant to infections or abnormalities such as cancer, and on the other not becoming over-active, and attacking the body’s own tissues.  Scientists are only just beginning to understand the implications for our risk of cancer of disruptions to this balance.

“This new study suggests there may be a genetic link between multiple sclerosis and Hodgkin lymphoma, suggesting a shared immune mechanism might be at work that could be exploited in treatments for both diseases.”

Professor Chris Bunce, Research Director at Leukaemia & Lymphoma Research, said:

“Survival rates for Hodgkin lymphoma are higher than ever before, but too many people are still dying and treatment used can have lifelong side effects.  Identifying the genes and pathways key to the development of Hodgkin lymphoma is vital to be able to design new, less toxic, drugs.”

Notes

Initial SNPs identified from Genome Wide Association Studies (GWAS) of 1,465 Hodgkin lymphoma patients and 6,417 control subjects. Two further UK replication studies of 3489 Hodgkin lymphoma patients and 1,853 control subjects were carried out.

ICR researchers identified susceptibility loci, or regions of DNA with genetic variations, for Hodgkin lymphoma at rs3806624 (chromosome 3p24.1) and rs7745098 (chromosome 6q23.3).

The three genomic regions previously found by ICR researchers were located at rs1432295 (chromosome 2p16.1), rs2019960 (chromosome 8q24.21) and rs501764 (chromosome 10p14).
http://www.ncbi.nlm.nih.gov/pubmed/21037568

Source: www.icr.ac.uk