Genetic Findings Explain Inherited Predisposition to Myeloma

Multiple myeloma (MM) is a malignancy of plasma cells that has a significant genetic component as evidenced by the two- to four-fold increased risk shown in relatives of MM patients.

Every year around 5,500 people in the UK are diagnosed with myeloma, a rare and incurable form of cancer affecting the plasma cells in bone marrow, and around one in 115 men and one in 155 women in the general population will develop myeloma in their life time.


A large team of international scientists led by those at The Institute of Cancer Research (London, UK) have identified eight new genetic variations in the human genome that could be linked to an increased risk of developing myeloma. The teams compared the genomes of myeloma patients with those of healthy individuals. The team also combined and re-analyzed data from similar research undertaken as part of a genome-wide association study (GWAS). In total, the researchers compared DNA from 9,866 myeloma patients with 239,188 healthy adults.

DNA was extracted from venous blood samples and genotyped in some countries using Illumina Human OmniExpress-12 v1.0 arrays (Illumina, San Diego, USA). Each country’s team used the most appropriate microarray for their part of the study. Eight single nucleotide polymorphisms (SNPs), inherited single letter variations in DNA, were linked to increased susceptibility of developing myeloma. These SNPs were located in regions of the genome involved in regulating genes linked to cell processes known to go wrong in myeloma development. These included the production of antibodies in plasma cells, as well as the regulation of gene activity and the maturation of these cells.

In total 17 risk variants for myeloma have now been identified by the scientists. It is estimated that the risk variants identified so far account for just 20% of the heritable risk factors connected to myeloma and further GWAS studies of patients are planned. The authors suggest that subtle effects on the activity of key genes could mean that the proper development of plasma cells breaks down, increasing the likelihood of developing myeloma.

Richard Houlston, MD, PhD, a Professor of Molecular and Population Genetics and study leader, said, “Our study expands our understanding of how inherited risk factors can influence the risk of myeloma. We know that the inherited risk of myeloma does not come from just one or two major risk genes, as can be the case with breast cancer, but from multiple different genetic variants, each with only a small individual effect on risk. Identifying more of these variants gives us new insights into the potential causes of the disease, and open up new strategies for prevention.” The study was published on July 1, 2016, in the journal Nature Communications.

Related Links:
The Institute of Cancer Research
Illumina