IMF DNA bank identifies genetic variations

The IMF today announced that researchers are reporting individual genetic differences that may be associated with risk factors for developing myeloma and with adverse reactions to therapies in patients who have myeloma. The findings were made with resources from Bank on a Cure®, the world's first repository of myeloma-patient DNA collected globally through large clinical trial groups, clinical centers, hospitals, and individual patients. The data were reported at the 47th Annual Meeting of the American Society of Hematology.

The findings presented at ASH demonstrate that differences in predisposition to myeloma and its treatments may be traced to single nucleotide polymorphisms or SNPs ("snips"), changes in a single letter in the DNA code of a gene. For example, the higher incidence of myeloma among African Americans may be related to SNPs that increase production of interleukin 6, or alter cell regulation. Some SNPs may also indicate the potential for neuropathy, nausea, bone pain and other toxic reactions to combination chemotherapy, while other SNPs indicate risk for blood clots associated with other therapies. In all, seven genetic variants that may influence myeloma risk and response were identified with significant differences seen among ethnic populations.

"We are expanding on these initial findings through the development of a custom panel of 3,500 SNPs that will enable simultaneous analysis of a larger number of factors than was possible until now, and we have begun testing this custom 'gene chip'," said Gareth Morgan, M.D., of the Royal Marsden Hospital in London, co-director of the Bank and co-author of Bank on a Cure presentations at ASH. "As we develop this custom SNP analysis, we will be able to move closer to the goal of personalized medicine, where finally we can better tailor treatments to individual patient needs."

The data from Bank on a Cure also showed unexpected findings. For example, although TNF-alpha, a protein associated with inflammation is elevated in myeloma patients, it may actually delay onset of the disease because of its role in other immunological processes.

"What this says to us is factors affecting myeloma are likely to be of the result of complex interactions of multiple genetic factors that are associated with risk and adverse response to treatments," said Brian Van Ness, Ph.D. of the University of Minnesota, co-director of the Bank and co-author of Bank on a Cure presentations at ASH. "Bank on a Cure has been invaluable in providing the large numbers of samples required for these studies, along with equipment and analytical tools, and the Bank's unique resources will be even more important as we use the new custom chip to look at larger numbers of genetic variations that are likely responsible for the development of myeloma and the outcome of treatment."

More than 3,000 DNA samples have been collected so far from myeloma patients in groups that have been treated with conventional medications, high dose therapies or with the novel medications. The samples along with the custom gene chip analyzers and other high tech equipment are housed at the University of Minnesota under the direction of Dr. Van Ness, and at the Institute of Cancer Research in London under the direction of Dr. Morgan. The International Myeloma Foundation expects the number of samples collected to double in the next two years.

DNA samples are stored anonymously and patient information is kept at a third, separate location to maintain confidentiality of the individuals who contribute samples to the Bank.