Photo courtesy of NIGMS
Investigators have identified a single nucleotide polymorphism (SNP) that seems to confer shorter survival in patients with multiple myeloma (MM).
The group found a significant association between survival and a SNP near the gene FOPNL on chromosome 16p13.
On average, MM patients with this SNP (rs72773978) died 1 to 3 years sooner than patients without it.
The investigators pinpointed the SNP via genome-wide association studies and verified its impact on survival in patient populations from North America and Europe.
The research, which is published in Nature Communications, included 1635 MM patients.
“This is the largest study of inherited genetics and myeloma survival to date,” said Nicola Camp, PhD, of the Huntsman Cancer Institute in Salt Lake City, Utah.
“We were able to identify the FOPNL variant because it has quite a large effect on survival. With even larger collaborative studies, we hope to add to this. The ability to stratify patients based on their genetic make-up opens the door to personalizing their treatment and care.”
For this study, Dr Camp and her colleagues first conducted a meta-analysis of 306 MM patients treated at University of California, San Francisco and 239 patients treated at the Mayo Clinic.
The investigators found a significant association between rs72773978 and survival. Patients with the minor allele had an increased risk of mortality compared to patients who were homozygous for the major allele (hazard ratio=2.65).
The team then conducted a replication meta-analysis of 1090 MM cases, including 772 European patients from the IMMEnSE consortium and 318 from the Utah cohort. Again, there was a significant association between rs72773978 and survival (hazard ratio=1.34).
Although the investigators don’t yet understand why the SNP is associated with poor prognosis, there are clues that it could be involved in disease progression through centrosome amplification.
Analyses of the different MM patient datasets showed that individuals with the worst outcomes have abnormal amounts of FOPNL and carry another sign of poor prognosis—a high centrosome index. The implication is that disruptions in FOPNL could affect fundamental mechanisms controlling the distribution of genetic material to newly made cells.
“The results point us to a previously unrecognized gene as a determinant of myeloma prognosis,” said Elad Ziv, MD, of the University of California, San Francisco.
“If we understand what about this gene is causing poor prognosis, that may lead to a better fundamental grasp of the pathways that are important in multiple myeloma progression. Such knowledge could ultimately lead to better therapies.”
