TCD Researchers identify genetic changes that increase risk of
development of Multiple Myeloma, a common blood cancer in Ireland
A genetic study on Multiple Myeloma has indicated that defects in DNA repair genes may
significantly contribute to the development of this life threatening disease. Speaking at
the Interlymph Conference in Vancouver, Canada, Prof Mark Lawler, Institute of
Molecular Medicine, St James’s Hospital and Trinity College Dublin, Lead Investigator
in the study, outlined how a candidate pathway approach, performed on DNA samples
from over 400 patients and controls has identified a number of key genetic variations in
genes involved in the DNA repair pathway and linked them to increased risk of
development of myeloma. Multiple Myeloma (MM) is a B cell malignancy, which
accounts for approximately 1% of cancer deaths worldwide. Ireland has one of the highest
incidences of this plasma cell malignancy and clues to how it occurs can help guide
optimal diagnosis and the development of new therapeutic approaches. This study,
performed in collaboration with Dr Paul Browne, St James’s Hospital, Prof Anthony
Staines, Dublin City University, Prof Stephen Chanock, National Cancer Institute, USA
and involving investigators in Epilymph, a European collaborative group, has pinpointed
subtle changes in a number of genes including XRCC4 and XRCC5 (2 genes involved in
DNA repair) and linked this to risk of myeloma development (initially published in
Human Molecular Genetics, a premier genetics journal) and highlighted how this may
also have relevance in patient response to therapy (recently published in Blood, the
leading international haematology journal).
“These results are very promising”, said Prof Lawler, highlighting the role that funding,
initially from the Irish Cancer Society and now from the Health Research Board had
played in this research. “The study has allowed us to look at a disease that is increasing
in incidence in the Irish population and implicate for the first time genetic changes in
DNA repair genes in its aetiology” he added. Dr Paul Browne, key collaborator on the
study from St James’s Hospital, added that “understanding the potential contribution of
DNA damage and repair to the development of myeloma will have important implications
in assessing the best use of new treatments for this condition. We are very pleased to be
involved in this international project which will hopefully benefit our patients, both in
understanding the cause of their disease, and in the study of novel therapies”.
At the conference in Vancouver, it was agreed that the Irish group would lead a
collaborative study as part of the International Multiple Myeloma Consortium (IMMC)
that would comprehensively delineate the role of DNA repair and DNA damage
response genes in myeloma development. Commenting on the results, Prof Stephen
Chanock, Chief Laboratory of Translational Genomics, National Cancer Institute, USA
and a collaborator on the study, said “We are excited to find that genetic variation in the
genes that repair DNA contribute to cancer risk, which gives us new clues to pursue for
diagnosis, treatment and ultimately prevention of this type of cancer”. In addition, a
collaboration with Dublin City University and a number of international investigators
will look at the role that both genetics and environment may play in the aetiology of this
disease, particularly given its increased incidence in Ireland. “We have already shown,
working with the International Multiple Myeloma Consortium, how people working in
certain jobs, notably farmers, printers and cleaners, are at increased risk of myeloma,
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due to different environmental exposures”, said Prof Anthony Staines, Professor of
Health Systems Research at Dublin City University. “This research will help us to
understand the crucial gene-gene and gene-environment effects that lead to the
development of myeloma”. “The study highlights the role that collaboration between
researchers worldwide in different disciplines can play in pinpointing the relevant risk
factors for cancer development and emphasises the importance of collaborative groups
such as Epilymph, Interlymph and the IMMC”, added Prof Lawler.
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