Genetic test could predict adverse reaction from bone cancer
2 March 2011
Genetic tests could predict whether bone marrow cancer
treatments including thalidomide are likely to give patients a
A study led by The Institute of Cancer Research (ICR) found that
each type of drug causes neuropathy in a different way and that
tests could be developed to indicate whether patients have genes
that show susceptibility for adverse reactions to specific drugs.
The study is published in the Journal of Clinical Oncology
Around 4,000 British people are diagnosed each year with multiple
myeloma, an aggressive cancer that affects a type of white blood
cell in the bone marrow called plasma cells. Average survival after
diagnosis is just three to five years, despite patients receiving
intensive treatment with a combination of drugs.
All common treatment regimens for multiple myeloma also contain
at least one drug with the side-effect of peripheral neuropathy — a
disorder of the nervous system that can cause altered sensation,
tingling, numbness and severe pain.
Almost one-third of patients of patients in this study who were
treated with the immune stimulating therapy thalidomide developed
neuropathy, along with around one-third of patients whose treatment
regimen contained the chemotherapy drug vincristine. In contrast,
only 6.4% of patients whose treatment combination did not include
thalidomide or vincristine developed neuropathy.
Symptoms sometimes clear when the patient stops the treatment or
reduces their dose, but neuropathy can be permanent and crippling,
and until now it has not been possible to predict which patients
will be afflicted.
In this study, the researchers analysed DNA from around 1,500
patients with multiple myeloma, searching through almost 1,000 genes
that have previously been linked cancer growth and treatment
When they examined patients who had been treated with
thalidomide, they found five regions of DNA were more common in
patients who had suffered neuropathy than those who had not
developed the condition. Interestingly, the regions are part of
genes involved in repair, development and inflammation of the
peripheral nervous system.
To determine whether the genes found were drug-specific, they ran
the same scan on patients treated with vincristine and found a
different set of genes — nine in total — were more common in
patients who developed neuropathy. The finding indicates that each
drug type causes neuropathy through a different biological pathway.
The study raises the possibility patients could have their blood
screened for neuropathy risk genes.
“Doctors could use this simple and useful test to identify
patients at high risk of neuropathy,” The ICR’s Professor Gareth
Morgan, who is also Head of the Haematology Unit at The Royal
Marsden Hospital NHS Foundation Trust, says. “At-risk patients could
be closely monitored, and potentially given alternative treatments,
lower doses or additional therapy to reduce side-effects. This
knowledge may also help us develop treatments that could protect
patients from neuropathy.”
This study also has implications for other cancer types as
vincristine, for example, is commonly used to treat acute
lymphoblastic leukaemia and lymphoma.
The study was funded by the Medical Research Council (MRC),
International Myeloma Foundation, Myeloma UK and the National
Institute for Health Research through its support of the Biomedical
Research Centre at The Royal Marsden and the ICR.
1. Genetic Factors Underlying the Risk of Thalidomide-Related
Neuropathy in Patients With Multiple Myeloma. Journal of
Clinical Oncology. March 1 2011.