Snip judgment

Studies link SNPs to myeloma risk, therapy response

Lloyd Dunlap
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NORTH HOLLYWOOD, Calif.—Genetic variants that may influence myeloma risk and response have been identified in research sponsored by the International Myeloma Foundation (IMF).

Preliminary findings also indicate that significant differences exist among ethnic populations, with the higher incidence of the disease among African Americans due to SNPs that alter cell regulation. The findings may also explain associations that have been observed between environmental toxins such as dioxins and benzene and an increased risk for myeloma, particularly among high-exposure groups such as firefighters.

IMF's Bank On A Cure (BOAC) effort was launched by the organization as its "signature program," says Dr. Brian G.M. Durie, chairman of IMF, with the specific objective of studying SNPs. Under its auspices, DNA samples have been collected from myeloma patients and analyzed for genetic variations that may contribute to response to treatment, susceptibility to toxic side effects, and factors that may contribute to a predisposition to the disease. "We wanted to learn why certain people get myeloma, which is a very rare disease." Durie notes. "Why do some patients respond while others don't? Why do some suffer complications?"

IMF received grants from the Centers for Disease Control and NIH to launch BOAC in an effort to solve these riddles. Working closely with Affymetrix, researchers developed custom chips for Affymetrix's DNA analyzers. SNPs were selected that are known to influence specific effects. "This was not a genome-wide search," Durie says, "but a highly customized approach."

Because myeloma is very rare, an international team was put in place to conduct the broadest study possible. One Affymetrix system went to Dr. Brian Van Ness' lab at the University of Minnesota and the other to The Royal Marsden Hospital in London under the direction of Dr. Gareth Morgan. Dr. Dalsu Baris at the National Cancer Institute lead the epidemiology effort. Startup cost for the program was about $2 million.

The research also turned up some preliminary but intriguing findings that show one of the cell signaling pathways associated with myeloma is also the natural target of thalidomide, approved by the FDA as a first line treatment for myeloma. In a developing fetus, thalidomide acting on this target leads to deformed limbs, but in myeloma where the target is defective, the thalidomide appears to block the development of the cancer.  BOAC is now capable of further investigation of susceptibility factors, Dr. Durie observes.  


Lloyd Dunlap

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