Leading leukemia researcher probes cluster cases: Preliminary results show genetic, metabolic similarities in Fallon cluster children

A leading Arkansas cancer researcher has uncovered preliminary data indicating children of Fallon's leukemia cluster may be genetically and metabolically predisposed to an increased risk of damage from environmental contaminants found in the area.

S. Jill James, a professor in the department of pediatrics at the Arkansas Children's Hospital Research Institute, was awarded $224,000 from the Environmental Protection Agency in 2004 to study genetic and metabolic factors that could increase the risk of leukemia among children of the Fallon cluster.

Her preliminary results were presented in a progress report to the EPA this summer.

Since 1997, 17 children in Churchill County have been diagnosed with acute lymphocytic leukemia and three have died. The latest case surfaced in December 2004 after more than two years without an addition to the cluster.

James and a medical team arrived in Fallon in October 2004 and visited the homes of six remaining cluster families to collect blood samples. Twenty samples were collected from six cluster children and their families. Families from Fallon were recruited for a total of 28 control samples.

DNA samples from 205 subjects in Arkansas were used as a population control.

An important result of the genetic analysis was that a well-established protective genetic factor was lacking in all of the case children tested, suggesting they may lack an important protective factor against the development of ALL, James said.

"Our hypothesis is that many of the environmental contaminants in Fallon interact to cause chronic oxidative stress in genetically susceptible children," James said.

Oxidative stress occurs when the body's antioxidant defense capacity is inadequate or depleted by environmental exposures. This imbalance can lead to oxidative DNA damage, a known risk factor for leukemia, she said.

James said the cluster children and families represent a very small test group, making it difficult to obtain conclusive answers. She's hoping to test additional case families, including those more recently diagnosed with ALL, and some leukemia cases that were not included in the cluster.

"We need to increase the sample size to get statistical significance with the genetic results," she said.

In addition to genetic analysis, James and her team evaluated how the metabolism of cluster children could be affected by chronic exposures to arsenic, tungsten/cobalt, uranium, mercury and JP-8 jet fuel. Each of the substances has been shown to deplete glutathione, the body's major antioxidant and detoxification mechanism which protects cells from oxidative DNA damage, James said.

Elevated levels of arsenic and tungsten were reported in biological samples taken from Fallon residents by the Centers for Disease Control in 2002. When the results were presented at a town hall meeting, CDC officials said little was known about the health effects from exposure to tungsten.

The metabolic results in James' research showed that cluster children had low levels of free glutathione and a highly significant increase in the oxidized, inactive form of the antioxidant.

This is a strong indication that case children are under chronic oxidative stress and would be less able to de-toxify the environmental contaminants in Fallon, she said.

The decrease in free glutathione and increase in oxidized glutathione among cluster children compared to age-matched control children was statistically significant in James' study.

She would also like to take a second blood sample this year and continue research to determine whether interaction between the multiple environmental contaminants in Fallon would increase oxidative stress and promote glutathione depletion in cells from case children compared to control children.

James says she far from uncovering the cause of the cluster, but her evidence suggests that cluster children may be uniquely more vulnerable to oxidative damage by the contaminants in Fallon.

"It's like any research," James said. "You present the results that you have, but it's really contingent upon repetition of other laboratories."

James and her team returned March 29-31, 2005 and presented findings to the parents of cluster children and invited guests.

"We were just welcomed into their homes," she said. "They had breakfast for us. They were just exceptionally nice and wonderful, wonderful people. It meant a lot to us to come to their homes and spend time with them to get their feedback. The families are extremely well informed and we learned from them."

Fallon resident Brenda Gross, whose son Dustin was diagnosed with leukemia at age 3 in 1999, said any research done on the cluster helps narrow down the causes and could lead to an explanation.

"What she showed me prior to doing the research was very exciting," Gross said. "It definitely is going to be beneficial."

Josh Johnson can be contacted at jjohnson@lahontanvalleynews.com