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Gene Variation Linked to Neuroblastoma, a Childhood Cancer

The variant is common in the aggressive form of the disease, researchers report

WEDNESDAY, May 7 (HealthDay News) -- For the first time, a gene linked to the often fatal childhood cancer neuroblastoma has been identified, researchers report.

"This is the first paper that helps us understand what causes this childhood cancer," said lead researcher Dr. John M. Maris, director of the Center for Childhood Cancer Research at The Children's Hospital of Philadelphia. "We expected for decades that this cancer was a genetic disease, but we have had a hard time understanding what abnormalities in our genetic makeup lead to this cancer."

Neuroblastoma, a cancer of the peripheral nervous system that usually appears as a solid tumor in the chest or abdomen, is the most common solid tumor malignancy seen in early childhood. Among infants, it can disappear with minimal treatment, but in older children, it can be an aggressive cancer spreading throughout the body. Neuroblastoma accounts for 7 percent of all childhood cancers but causes 15 percent of all childhood cancer deaths. There are about 700 new cases diagnosed each year in the United States, the researchers said.

Maris' team found a common genetic variation of the gene 6p22 on chromosome 6, which doubles the risk of getting this disease. "This finding supports our assumption that there are a number of minor variations that work together -- in sort of a perfect storm -- to give a child this disease," he said. "This finding is the discovery of the first of these genetic variants."

Maris noted that this is the first time a childhood cancer has been found to be influenced by rather common genetic changes "that can be in you or me or anyone."

In addition, Maris said that having this particular genetic variation not only increases the risk of developing neuroblastoma, but also increases the risk of developing the more aggressive form of the disease. "This leads us to believe that the disease we call high-risk or low-risk neuroblastoma are really different diseases," he said.

The findings were published in the May 7 online edition of the New England Journal of Medicine.

For the study, Maris' team analyzed blood samples from 1,032 children with neuroblastoma and 2,043 children without the disease. The researchers honed in on three single nucleotide polymorphisms (SNPs) -- which are variations in DNA -- that were more common in patients with neuroblastoma than in patients without the disease. The three SNPs were clustered in the 6p22 region of chromosome 6. There are two genes in this region, but exactly what they do is unknown, the researchers said.

To confirm their findings, Maris' group analyzed blood samples from additional neuroblastoma patients and children without the disease. Among these additional patients, the researchers also found that variants in the 6p22 region were associated with increased risk for neuroblastoma.

"This finding gives us the motivation to continue this line of research to discover all of the different genetic variations that work together," Maris said. "We have already discovered additional variations."

Knowing the complete genetic influences on neuroblastoma may eventually lead to new treatments, he said.

Dr. Len Lichtenfeld, deputy chief medical officer of the American Cancer Society, said that the new findings could one day lead to better diagnosis and treatment of the malignancy. "We still need to understand what these genes do, because little is known about these genes," he said.

Lichtenfeld added that, while the new research is important, it's still very preliminary. "Ultimately, what you want to do is to analyze the cancer and gain clues as to what the prognosis may be and what the appropriate treatment may be," he said. "This does not get us there, but it is one step along that pathway."

More information

For more on neuroblastoma, visit the American Cancer Society.

SOURCES: John M. Maris, M.D., director of the Center for Childhood Cancer Research, The Children's Hospital of Philadelphia; Len Lichtenfeld, M.D., deputy chief medical officer, American Cancer Society, Atlanta; May 7, 2008, New England Journal of Medicine, online

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