Leading leukemia researcher probes cluster cases: Preliminary results show
genetic,
metabolic similarities in Fallon cluster children
Story in Lahontan Valley News,RE: Fallon Nevada Cluster, Parent Info

JOSH JOHNSON
JOSH JOHNSON, jjohnson@...

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@...