U. S. researchers said on Tuesday that genetic variations affect the way children respond to treatment for the most common type of childhood cancer. This finding could help in better treatments for treatment of acute lymphoblastic leukemia or ALL, which is a cancer of the blood and bone marrow.

Although 80 % of the children suffering from this type of cancer get cured, some do not respond to treatment. Researchers at St. Jude Children's Research Hospital in Tennessee and colleagues said that while most studies examine genetic mutations acquired by leukemia cells they in this study looked for inherited genetic variations that affect all cells in the body.

"For the first time, we used a genome-wide strategy to interrogate over 500,000 variations in inherited DNA to find common gene variations called SNPs, or single nucleotide polymorphisms, that predicted response to chemotherapy," said lead researcher Mary V. Relling, who chairs the pharmaceutical department at St. Jude Children's Research Hospital in Memphis, Tenn.

The researchers looked at 476,796 inherited variations called single-nucleotide polymorphisms, or SNPs. These influence the number of cancer cells left over after the first course of chemotherapy, a marker known as minimal residual disease. The researchers attempt was to find evidence of disease that persisted after treatment.

They collected samples from two independent groups of 487 children with newly diagnosed ALL and the researchers found 102 inherited genetic variations that appeared to be involved in response to leukemia treatment. "We took those 102 and we tested whether they were involved in other related characteristics," said Relling.

The researchers found that 21 of these were associated with relapse while another 21 were linked to strong, early response to treatment. . "A high proportion of the gene variations were related to levels of the chemotherapy in blood and in leukemia cells; some were related to leukemia cell biology," Relling said.

Overall the researchers found that 61.7 % of the SNPs were linked to early response, relapse risk or the performance of antileukemic drugs. They also found a cluster of variations around a gene called IL15, which makes a protein called interleukin 15 that causes leukemia cells to multiply. Previous studies have suggested that IL15 protects tumors from chemotherapy drugs.

Relling said, "Our findings imply that the DNA patients inherit from their parents also explains why some patients respond to chemotherapy better than others. We also found some interesting genes that were previously under-appreciated and may provide new targets for new drug development."

The researchers feel that it is important to know the genetics of patients as well as know the genetics of their tumors in order to design effective treatments. "When modern genomics is used to try to personalize medication regimens for cancer, we will need to consider the genetic variation that each patient has inherited, in addition to the genetic variation that is unique to the tumor cells," Relling said. "It will be necessary to continue to do genomic research in as many patients with cancer as possible in order to be able to apply these results in the future."

Dr. Barton Kamen, chief medical officer of the Leukemia & Lymphoma Society said, "The problem is that the high cure rate of lymphoblastic leukemia still has a price. But knowing the genetic makeup of people and their disease, he said, might make it possible to make treatment less toxic by using lower doses for a shorter time.

Jun Yang of St. Jude said, "Such information might help clinicians use drugs more effectively to overcome the patient's own genetic variation and reduce the chance of treatment failure."

The study appears in the Journal of the American Medical Association. (Additional reporting by Harkiran)