Genetic Link Found Between Immune System and Lymphoma

Classical Hodgkin lymphoma (cHL) is a lymphoid malignancy of germinal center (GC) B-cell origin, which is characterized by Hodgkin and Reed–Sternberg (HRS) cells with a dominant background population of reactive inflammatory cells.

People who inherit genetic changes that alter the function of their immune system are at increased risk of developing Hodgkin lymphoma. Of the four major subtypes of cHL, nodular sclerosis Hodgkin lymphoma (NSHL) and mixed cellularity Hodgkin lymphoma (MCHL) account for 65% and 20% of cHL, respectively.

A large group of scientists collaborating with The Institute of Cancer Research (London, UK) analyzed genetic data from 5,314 cases of Hodgkin lymphoma and 16,749 controls, from four different European studies. They analyzed constitutional DNA from 1,717 cases, which were genotyped using the Illumina Oncoarray (Illumina Inc, San Diego, CA, USA). The fidelity of genome-wide association study (GWAS) imputation was assessed by the concordance between imputed and directly genotyped single nucleotide polymorphisms (SNP) in a subset of samples. Replication genotyping of UK samples was performed using Polymerase Chain Reaction Kompetitive Allele Specific (PCR KASP) chemistry.

The investigators identified six new single-letter changes in DNA that were linked to the development of Hodgkin lymphoma and five of these affect the way a type of white blood cell, called B cells, develop. The study also showed clear differences in genetic risk between two different subtypes of Hodgkin Lymphoma and NSHL and MCHL. For example, a single-letter change located in DNA near the gene LIM Domain Containing Preferred Translocation Partner In Lipoma (LPP) increased the risk of NSHL by 37%, but had little effect on the risk of developing MCHL.

Richard S. Houlston, FMedSci, FRS, a Professor of Molecular and Population Genetics and senior author of the study, 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. The new information could point towards new ways of diagnosing, treating, or even helping to prevent Hodgkin lymphoma.” The study was published on December 1, 2017, in the journal Nature Communications.

Related Links:
The Institute of Cancer Research
Illumina Oncoarray