Researchers from St. Jude Children’s Research Hospital in Memphis, Tenn. report that inherited genetic differences may help determine how well children with a specific type of blood cancer will respond to treatment. A study in the January 28th issue of the Journal of the American Medical Association links differences in more than 100 genetic markers with the response to chemotherapy treatment in children with acute lymphoblastic leukemia (ALL), the most common type of childhood cancer.

Understanding inherited genetic differences in the response to cancer can help doctors understand why treatments fail on some patients and lead to better treatment strategies, such as determining at the outset which patients may require more aggressive treatment. It may also help researchers develop new ways of treating patients such as drugs that mimic the genetic variations associated with better treatment responses.
 
While the survival rate for ALL has climbed from less than 10 percent in the 1960s to over 80 percent today, there is still considerable variation in how individual patients respond to treatment for the disease. To find out why, researches examined variations in the inherited genetic make-up of children undergoing treatment for ALL and compared these to the number of cancer cells left over after the first course of chemotherapy (known as the minimal residual disease). More than 100 variations called single nucleotide polymorphisms (SNPs) were found to be associated with differences in treatment outcome.

About 20 percent of the markers were related to a tendency for relapse, and a similar number of markers were associated with a very strong, early response to treatment. In addition, 20 percent of the markers were associated with how the body responds to chemotherapy drugs used to treat leukemia. Gene variations associated with faster elimination of the drugs from the body were associated with worse treatment outcomes, suggesting that patients with these variations may only need a higher dose of chemotherapy to achieve the same result as other patients.

The researchers also found that variations associated with the gene for a molecule called interleukin 15 (IL15) already known to protect certain tumors from chemotherapy drugs was associated with higher levels of this of this molecule in leukemia cells, and a poorer outcome after therapy.

The study is unique in that most research into the genetics of cancer treatment focus on acquired variations in cancer cells that occur only after birth and affect only the cancer cells themselves. The present study looked instead at variations in the inherited genetic profile that are present from before birth and found in every cell of the body.
 
While the results of the study are encouraging, it may be a while before genetic testing of cancer patients to determine treatment strategies becomes common. Researchers need to verify that the genetic differences really do equate to differences in long-term survival, but if so, expect to see other researchers using similar methods to study the association between genetic variations and treatment response in other cancers.

For more information about ALL and cancers of children, join the Healia Health Community for Childhood Leukemia or the Healia Health Community for Childhood Cancer.

_{Photo: VashiDonsk, Wikimedia Commons, GNU Free Documentation License}