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Studies Examine Whether Persistent Organic Agents
May Be Responsible for Rise in Lymphoma Rates
The incidence of non-Hodgkin
lymphoma (NHL), a cancer involving
white blood cells of the immune
system, has steadily risen, nearly
doubling over the past 30 years. Some
of the change is related to AIDS, which
substantially increases the risk of NHL,
and some may have resulted from
better diagnosis, but the reasons for the
long-term rise are largely unknown.
Some researchers speculate that the
increase is due in part to exposure to
environmental agents.
Epidemiologic evidence points to
one possible culprit—a class of chemicals called organochlorines, which include certain pesticides, polychlorinated
biphenols (PCBs), and dioxins. Many
have been manufactured in large scale
since the 1930s, and their chemical
properties make them resistant to
degradation by water, sun, and microorganisms. So, even though most were
banned or their use restricted in the
l970s and l980s in developed countries,
they are persistent pollutants in the air,
water, and soil, and they accumulate in
the fatty tissue of animals and humans.
The most widespread organochlorines
in the environment and human tissues
are PCBs, DDT, and DDE, a breakdown
product of DDT.
According to the Agency for Toxic
Substances and Disease Registry, “most
of the human studies involving PCBs
have many shortcomings, which make it
difficult for scientists to establish a clear
association between PCB exposure levels and health effects.” However, from
the evidence of liver cancer in animals,
the National Toxicology Program’s
Report on Carcinogens lists PCBs as
“reasonably anticipated to be a human
carcinogen.” The Environmental Protection Agency has set standards for PCBs
in drinking water, and the U.S. Food
and Drug Administration has set limits
for PCBs in various foods. Besides
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cancer, human studies have found
associations between PCB exposure
and adverse developmental and reproductive effects as well as nervous
system damage.
PCBs were produced in the United
States from 1929 until 1977. Initially,
PCBs were used as coolants and lubricants in electrical equipment, such as
transformers and capacitors, but after
1957 they were used primarily in hydraulic fluids, flame retardants, paints,
plasticizers, pesticides, and wood
preservatives. Production stopped because of accumulating evidence that
exposure to PCBs is associated with
adverse health effects, including cancer.
Today, PCBs can still be released into
the environment from poorly maintained
hazardous waste sites, dumping of
wastes (e.g., old transformer fluid,
fluorescent lighting fixtures, appliances,
or televisions), or burning of waste in
municipal and industrial incinerators.
“Although PCBs and DDT were
banned in the United States in the 1970s,
exposure to these compounds was once
widespread, and they continue to be
ubiquitous environmental pollutants,”
said Joanne Colt, of the Division of Cancer Epidemiology and Genetics at the
National Cancer Institute.
Pesticide
exposure and
non-Hodgkin
lymphoma risk is
perhaps the most
well-studied association of the
organochlorines.
Organochlorine
pesticides—DDT,
chlordane, aldrin,
dieldrin, endrin,
dacthal, heptachlor, lindane,
methoxychlor,
Photo by Ken Hammond
and pentachlorphenol—were introduced to the United States
in the 1940s. EPA banned or restricted the use
of many of them during the 1970s and 1980s.
Colt led a study, published in the July
issue of Epidemiology, in which she and
her colleagues measured residential exposure to organochlorines by sampling
carpet dust from homes in Detroit, Iowa,
Los Angeles, and Seattle. Carpets and
underlying foam pads act as repositories
for these chemicals, which can enter the
home from indoor use, or by foot or air
from outdoors. Once in the carpet, they
may linger there for months or years,
resistant to degradation by sun, moisture, and microorganisms.
The researchers compared the agents
found in the carpet dust in the homes of
603 patients with NHL to those found in
the carpets of 443 control subjects. A
50% increased risk of NHL was associated with exposure to any of five types
of PCBs commonly found in environmental samples—PCB 105, 138, 153,
170, or 180. However, a statistically
significant dose response was seen only
at increasing levels of PCB 180, with a
70% increased risk of NHL at the highest exposure levels. A dose response
was also seen with DDE, with a 60%
elevation in risk at the highest levels.
“If the association observed in our
study is real, these compounds could
have contributed to the risk of NHL observed over the past several decades,”
Colt said. “Although contaminated carpet dust is not a major route of exposure
to these compounds for adults, their presence in carpet dust today could be
indicative of exposures that occurred
many years ago.”
A dozen or so previous studies of
NHL and specific organochlorine exposure in the general population have had
similar results. Colt’s study was the first
to look at NHL risk and organochlorine
levels in carpet dust. She and her colleagues expect to publish data on levels
of organochlorines in blood samples
from the same case patients and control
subjects later this year.
Journal of the National Cancer Institute, Vol. 97, No. 20, October 19, 2005
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“Although diet is assumed to be a
major contributor to organochlorine
exposures, this finding indicates that
nondietary exposures could be
important—a very interesting finding,
if true,” said Penelope J.E. Quintana,
Ph.D., of the Graduate School of Public
Health at San Diego State University
in San Diego.
Pesticides
Pesticide exposure and NHL risk
is perhaps the most well-studied
association of the organochlorines.
Organochlorine pesticides—DDT, chlordane, aldrin, dieldrin, endrin, dacthal,
heptachlor, lindane, methoxychlor,
and pentachlorphenol—were introduced
to the United States in the 1940s and,
like PCBs, persist in the environment
long after they are applied. The EPA
banned or restricted the use of many of
them during the 1970s and 1980s—
DDT was banned in 1972, endrin in
1986, dieldrin and aldrin in 1987, and
chlordane in 1988. People can be exposed to organochlorine pesticides by
eating fatty foods, such as milk, dairy
products, or fish that are contaminated
with these pesticides; by eating food
imported from countries that still allow
the use of persistent pesticides; or by
absorbing these pesticides through
the skin.
In studies in farmers, NHL has
been associated with three different
chemical classes of pesticides, including
organochlorine pesticides. However,
it is not clear which particular pesticide
may be responsible for the elevated risk
or whether other farm exposures such
as dust, solvents, fuels, animal viruses,
and fertilizers may play a role. The
organochlorine pesticides chlordane,
dieldrin, and lindane have been
associated with NHL in past studies,
but not consistently.
Despite this uncertainty, many
pesticides—including organochlorines—
are classified as possible or probable
carcinogens because of evidence in
animal studies. But many countries in
Asia, Africa, and South and Central
America continue to use organochlorine
pesticides for crops and malaria control.
In Mexico, where DDT is still used, high
concentrations of DDT in human breast
milk have been reported.
PBDE
Not all persistent chemicals
are regulated by governments. A
synthetic flame retardant, polybrominated diphenyl
ether (PBDE)
has come into
common use
in the United
States during
the last three
decades and is
accumulating
in human
blood, milk,
Arnold Schecter
and food.
PBDEs are
currently widely used in consumer
products, such as plastic foam,
computers, televisions, fabrics, and
carpet linings.
“U.S. human tissue levels of PBDEs
have increased markedly during the past
several decades, which reflects the increased use of PBDEs beginning in the
1970s,” said Arnold Schecter, M.D.,
from the University of Texas School of
Public Health in Dallas.
Unlike other persistent chemicals,
the routes of PBDE exposure are not
well studied, although food is thought
to be the major one. Animal models
confirmed that PBDE’s toxicology
profiles are similar to those of PCBs,
but there have been no human toxicity
or epidemiological studies to see
whether the increased levels of PBDEs
in humans are associated with cancer or
any disease.
The Larger Picture
Looking at the larger picture, there
is good news on two fronts. The incidence of NHL in several countries has
been leveling off. Data from the
Surveillance, Epidemiology, and
End Results (SEER) program at NCI
show that during 1975–1990, the
annual percent change in NHL was
+3.6% compared with +1.6% during
1990–1995 and –0.9% during 1995–
2000. Similar trends in NHL rates
are seen in Sweden, Denmark, and
Journal of the National Cancer Institute, Vol. 97, No. 20, October 19, 2005
Finland, where many organochlorines
are also banned.
Also, studies from Sweden, Germany,
the Netherlands, Japan, Canada, and the
United States have reported decreasing
levels of some organochlorines in
human tissue and the environment. A
survey of worldwide trends in DDT
levels in human breast milk from several
continents over five decades showed that
these concentrations have declined in
most areas of the world, consistent with
restrictions on its use. In the United
States, the Agency for Toxic Substances
and Disease Registry reported that
between 1978 and 1991, the estimated
daily intake of PCBs in adults from
dietary sources declined from about
1.9 ng to less than 0.9 ng.
Along the same lines, Schecter and
his colleagues reported in the March
issue of the Journal of Occupational
and Environmental Medicine that
the serum levels in 2003 of certain
organochlorines—PCBs, dioxins, and
dibenzofurans—were substantially
lower than samples from 1973.
Whether there is a relationship
between the changing NHL rates and the
levels of chemicals is not
certain, but
the hypothesis
seems reasonable to many
scientists.
One of those
is Lennart
Hardell, M.D.,
Ph.D., from
Lennart Hardell
the Department
of Oncology
at University Hospital in Orebro,
Sweden, who wrote a recent article in
Environmental Health Perspectives on
the declining rates of NHL. He said
that the leveling off of the incidence
curve of NHL could be explained by
the decreasing exposure to one or
several environmental agents, and may
be a “good example of how prohibition
and limitation of exposure may be
reflected in cancer statistics some
years later.”
—Nancy J. Nelson
© Oxford University Press 2005. DOI: 10.1093/jnci/dji364
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