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Researchers Identify Genetic Variations Associated With Predisposition to Myeloma and Response to Therapy

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The International Myeloma Foundation has 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 data were reported at the 47th Annual Meeting of the American Society of Hematology (ASH).

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."

"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."

"With a rare cancer such as myeloma it takes unprecedented collaboration on a global scale to collect the samples we need to develop robust data, and the Bank on a Cure has made that possible," said Brian G. M. Durie, M.D., chairman of the International Myeloma Foundation and co-director of Bank on a Cure.

"Our findings will help us understand the factors underlying the development of cancer and its treatment with implications that could take us beyond myeloma alone."