 |
Studies Linking PCBs,
Dioxin and Brain Cancer
The following brain cancer research was collected from the TOXNET
database of the National Library of Medicine. This may not be a complete
list of brain cancer studies involving PCBs, and these studies are not
all equal in size or quality. Some were published in peer-reviewed
journals, while others were presented at conferences. A few
are duplicates by the same author (one conference-based, another published)
but we presented both because the descriptions were slightly different.
Study #1
-
mortality from brain cancer was modestly increased among men with up to
10,000 hours PCB exposure
-
no deaths from brain cancer occurred among the most highly PCB exposed
men
-
a five-year lag time increased the brain cancer rate
OBJECTIVES: To assess whether excess mortality from cancer, malignant melanoma
of the skin, and cancers of the brain and liver in particular, is
associated with long term occupational exposure to polychlorinated biphenyls
(PCBs). METHODS: An epidemiological study of mortality was conducted
among 138,905 men employed for at least six months between 1950 and 1986
at five electrical power companies in the United States. Exposures were
assessed by panels composed of workers, hygienists, and managers at each
company, who considered tasks performed by workers in 28 job categories
and estimated weekly exposures in hours for each job. Poisson regression
was used to examine mortality in relation to exposure to electrical insulating
fluids containing PCBs, controlling for demographic and occupational factors.
RESULTS: Neither all cause nor total cancer mortality was related to cumulative
exposure to PCB insulating fluids. Mortality from malignant melanoma increased
with exposure; rate ratios (RRs) relative to unexposed men for melanoma
were 1.23 (95% confidence interval (95% CI) 0.56 to 2.52), 1.71 (0.68 to
4.28) and 1.93 (0.52 to 7.14) for men with < 2000, > 2000-10,000, and
> 10,000 hours of cumulative exposure to PCB insulating fluids, respectively,
without consideration of latency. Lagging exposure by 20 years yielded
RRs of 1.29 (0.76 to 2.18), 2.56 (1.09 to 5.97), and 4.81 (1.49 to 15.50)
for the same exposure levels. Mortality from brain cancer was modestly
increased among men with < 2000 hours (RR 1.61, 95% CI 0.86 to 3.01)
and > 2000-10,000 hours exposure (RR 1.79, 95% CI 0.81 to 3.95), but there
were no deaths from brain cancer among the most highly exposed men. A lag
of five years yielded slightly increased RRs. Mortality from liver
cancer was not associated with exposure to PCB insulating fluids. CONCLUSIONS:
This study was larger and provided more detailed information on exposure
than past investigations of workers exposed to PCBs. The results suggest
that PCBs cause cancer, with malignant melanoma being of particular
concern in this industry. (Loomis et al, 1997)
Study #2
-
More deaths were observed than expected for cancer of the brain and nervous
system
-
The average estimated cumulative dose for the cases of brain cancer was
greater than for other workers
On the basis of evidence from animal studies, polychlorinated biphenyls
(PCBs) are considered potentially carcinogenic to humans. However, the
results of studies in human populations exposed to PCBs have been inconsistent.
The authors conducted a retrospective cohort analysis (1957-1986) comparing
the mortality of 3,588 electrical capacitor manufacturing workers with
known exposure to PCBs with age-, sex-, and calendar time-specific
mortality rates for all whites in the United States. Proportional hazards
modeling was also performed to examine the association between cumulative
PCB exposure and site-specific cancer mortality. All-cause mortality (192
deaths observed, 283.3 expected) and total cancer mortality (54 deaths
observed, 63.7 expected) were lower than expected. More deaths were
observed than expected for malignant melanoma (8 observed, less than
2.0 expected) and cancer of the brain and nervous system (5 observed,
2.8 expected). The average estimated cumulative dose for the cases of brain
cancer (22.9 units) was greater than for other workers (12.9 units), but
the 95% confidence intervals around this difference were broad. The
risk of malignant melanoma was not related to cumulative PCB exposure.
These results provide some evidence of an association between employment
at this plant and malignant melanoma and cancer of the brain. The possibility
that the results are due to chance, bias, or confounding cannot be excluded.
(Sinks et al, 1992)
Study #3
-
PCBs are known to deposit preferentially in nervous tissue
-
Study examined two PCB-exposed workers with brain cancer
-
Researchers urge more studies of link between PCBs and brain cancer
Polychlorinated biphenyls have been shown to be carcinogens in animal studies.
Because of lipid solubility and lack of biodegradation, they are known
to deposit preferentially in fat and nervous tissue. In this
report, we describe a 31-year-old male with prolonged polychlorinated
biphenyls exposure who developed glioblastoma multiforme [brain cancer].
Fat biopsy documented the presence of markedly elevated PCB levels.
A co-worker also developed a malignant astrocytoma [brain cancer].
The nature of PCBs and their role in human carcinogenesis are discussed.
The
possibility of an etiologic link between PCBs and brain tumors should be
further investigated. (Petruska et al, 1991)
Study #4
-
increased incidence of brain cancer among workers who had more than twice
the estimated cumulative PCB dose than the comparison group
NIOSH conducted a retrospective cohort study of workers manufacturing electrical
capacitors with known exposure to polychlorinated biphenyls (1336363) (PCBs)
in an effort to further evaluate the carcinogenicity of PCBs. The study
cohort manufactured electric capacitors in the midwest United States beginning
in 1957. PCBs were used as a dielectric fluid until late in 1977 when they
were replaced with isopropyl-biphenyl (25640782). Aroclor-1242 (53469219)
was used through 1970 and Aroclor-1016 (12674112) was used afterwards.
Included in the analysis were 3588 men and women employed for at least
one day between January 1, 1957 and March 31, 1977. The results provided
some evidence for an association between PCB exposure in an occupational
environment and mortality from malignant melanoma. There was an increased
incidence of brain cancer among workers who had more than twice the estimated
cumulative PCB dose than the comparison group. The authors conclude
that this brain cancer observation suggests that this outcome be carefully
observed in further followup of this cohort. (Sinks et al, 1991)
Study #5
-
PCB-exposed workers experienced excess in the number of deaths resulting
from brain cancer
A study was undertaken of the mortality experience of 3588 male and female
workers at the Westinghouse Electric Corporation located in Bloomington,
Indiana from 1957 to 1977. There was possible exposure to polychlorinated
biphenyls (PCBs). The mortality was less than had been expected; however,
there was an excess in the number of deaths resulting from brain cancer
and
from malignant melanomas. Investigators were not able to demonstrate statistically
significant relations between excess mortality and PCB exposure. A notification
letter was mailed to 3189 individuals. Anecdotal information provided by
some cohort members indicated that the potential for both dermal and
airborne PCB exposure during capacitor manufacture was great. The authors
conclude that the decision to communicate risk information to members of
a cohort should be handled separately from, and after completion of review
of the scientific merits of the study. The vital status of the cohort should
be updated as close to the notification date as possible. (Mazzuckelli
et al, 1993)
Study #6
-
elevated risks of brain cancer have been noted in electrical workers, who
tend to be exposed to PCBs
A summary was provided of past research into residential and occupational
exposures to electromagnetic fields and the possible relationship between
exposure and the incidence of cancer. Information was presented concerning
exposure assessment, potential cofounders, and biological mechanisms. Sources
of electric and magnetic fields included household appliances, electric
power lines, electric blankets, and various types of office equipment.
One of the major criticisms of previous investigations on the incidence
of cancer in electrical workers had been that they were based on job titles
and did not therefore assessed individual exposures to electromagnetic
fields. However, elevated risks of leukemia and brain cancer
have been noted in electrical workers. The use of personal dosimetry
data will make the case more convincing. Potential cofounders which were
significant in occupational exposure investigations included life style
factors such as smoking, diet, social class and others not attributed to
a specific job. Other cofactors included exposures on the job to solvents,
polychlorinated
biphenyls, ionizing radiation and welding fumes, some of which may
be very closely correlated with exposure to electromagnetic fields in a
particular industry. Future investigations of cancer among electrical workers
should attempt to examine all possible work related causes of leukemia
and brain cancer to narrow the list of candidates. Possible mechanisms
of action and the time span between exposure and diagnosis of disease were
reviewed. (Savitz et al, 1989)
Study #7
-
Brain cancer was significantly increased in females exposed to dioxin
A study of mortality was conducted in persons involved in the Seveso accident
in which an accidental explosion at a Hoffmana Roche chemical factory at
Meda, Italy in 1976 contaminated a wide area with 2,3,7,8-tetrachlorodibenzo-p-dioxin
(1746016) (TCDD). The cohort consisted of 556 persons who lived in an area
with average soil TCDD concentrations of 15.5 to 580.4 micrograms per square
meter (microg/m2) (zone-A), 3920 persons living in an area having average
soil TCDD concentrations below 50 microg/m2 (zone-B), and 26,227 persons
who lived in an area having soil TCDD concentrations generally below 5microg/m2
(zone-R). The comparisons consisted of 167,391 persons living in surrounding
areas who did not experience any TCDD fallout from the explosion. All subjects
were 20 to 74 years old. Vital status of the cohort as of December 31,
1986 was determined. Death certificates of all decedents were examined.
Mortality from cardiovascular diseases was significantly elevated in subjects
living in zone-A. In zone-B residents, significant excess mortality from
total cancer, Hodgkin's disease, melanoma, and leukemia occurred among
males although the number of cases was small. Single deaths occurred among
females from gall bladder and biliary tract cancer, soft tumor sarcomas,
and thyroid cancer. In zone-R, slight deficits in mortality from total
cancer in both males and females and lung cancer in males and significant
decreases in breast cancer in females occurred. Mortality from soft tissue
sarcoma was significantly increased in males. Mortality from uterine and
brain
cancer was significantly increased in females. Mortality from cardiovascular
disease was increased. The authors conclude that the mortality pattern
of individuals exposed to TCDD differs from that of the population in the
surrounding territory. While no definite conclusions can be drawn, the
data suggest that TCDD can cause delayed health effects. (Bertazzi
et al, 1989
Study #8
-
A statistically significant higher concentration of PCB was found in extracted
lipids of adipose tissue samples from terminal brain cancer patients
A statistically significant correlation was demonstrated between the content
of PCB and DDE in lipids extracted from subcutaneous abdominal tissue of
terminal patients and their age. A higher concentration of PCB and
DDE was found in extracted lipids of adipose tissue samples from terminal
cancer patients (malignant lymphoma, retroperitoneal carcinoma, glioblastoma,
adenocarcinoma, cancer of the breast, mesothelioma, carcinoma of the cervix,
pulmonary carcinoma, cancer of the rectum, cancer of the colon, lymphosarcoma,
etc.) than in the adipose tissue of patients who died of other diseases.
This
difference was statistically significant. The results are discussed
and the need for further investigations of a possible cause-effect relationship
between exposure to organochlorine compounds and neoplasias is stressed.
(Unger et al, 1980)
Study #9
-
Nerve Growth Factor (NGF) was more potent in the presence of PCBs
-
PCBs have the potential to influence the NGF neurotrophic system
The effects of Aroclor 1254, a mixture of polychlorinated biphenyls (PCBs),
on nerve growth factor (NGF) receptors and neurite outgrowth in
PC12 cells were examined. Aroclor 1254 enhanced the NGF-stimulated neurite
elongation and decreased the Kd value for binding of 125I-labeled NGF
to the high-affinity NGF receptors. The NGF dose-response curve for neurite
outgrowth was also shifted to the left in cells pretreated with Aroclor
1254, suggesting that NGF was more potent in the presence of PCBs.
Thus, one mechanism by which PCBs may enhance NGF-stimulated neurotrophic
effects is in increasing the affinity of binding of NGF to the high-affinity
NGF receptors, which are believed to mediate the neurotrophic effects of
NGF. The data suggest that PCBs have the potential to influence the
NGF neurotrophic system. (Angus et al, 1995)
Study #10
-
children of fathers exposed to dioxin experienced increased rates of brain
cancer
BACKGROUND: A case-control study was conducted with 183 histologically
confirmed neuroblastoma cases aged
0-14 years diagnosed among residents of New York State, excluding New
York City, between 1976 and 1987. Three hundred seventy-two controls were
selected from the New York State live birth certificate registry and were
matched to cases on year of birth. METHODS: Parental occupational
exposures at the time of each child's birth were obtained from maternal
telephone interviews, successfully completed for 85% of cases and 87% of
controls. RESULTS: Odds ratios were significantly elevated for maternal
occupation in the service (OR = 2.0, 95% CI = 1.0 4.1) and retail (OR =
2.0, 95% CI = 1.1-3.7) industries and paternal occupation in materials
handling (OR = 3.8, 95% CI = 1.1-14.6). Odds ratios were also significantly
elevated for maternal report of occupational exposure to acetone (OR =
3.1, 95% CI = 1.7-5.6), insecticides (OR = 2.3, 95% CI = 1.4-3.7), lead
(OR = 4.7, 95% CI = 1.3-18.2) and petroleum (OR = 3.0, 95% CI = 1.5-6.1)
and paternal exposure to creosote (OR = 2.1, 95% CI = 1.1-4.3),
dioxin
(OR = 6.9, 95% CI = 1.3-68.4), lead (OR = 2.4, 95% CI = 1.2-4.8), and
petroleum (OR = 1.8, 95% CI = 1.1-2.8). CONCLUSIONS: Due to the uncertainty
of the biologic plausibility of these associations and the possibility
of alternative explanations, these results should be interpreted cautiously.
(Kerr et al, 2000)
Study #11
-
there is suggestive evidence that brain tumors are associated with parental
exposures to chemicals.
-
causes of endocrine-related cancers or susceptibility to cancer may be
a result of developmental exposures rather than exposures existing at or
near the time of tumor detection
Developing organisms have increased susceptibility to cancer if they are
exposed to environmental toxicants during rapid growth and differentiation.
Human studies have demonstrated clear increases in cancer after prenatal
exposure to ionizing radiation, and there is suggestive evidence that
brain tumors and leukemia are associated with parental exposures
to chemicals. Animal experiments have demonstrated increased tumor
formation induced by prenatal or neonatal exposure to a variety of chemicals,
including direct-acting carcinogens and drugs. Recently, natural estrogens
have been classified as known human carcinogens. Prenatal exposure to natural
and synthetic estrogens is associated with increases in breast and vaginal
tumors in humans as well as uterine tumors in animals. Synthetic halogenated
chemicals increase liver tumors after early life-stage exposure. Recently,
a prototypical endocrine-disrupting compound, 2,3,7,8-tetrachlorodibenzo-p-dioxin,
has been shown to be a developmental toxicant of the mammary gland in rodents.
Dioxin alters multiple endocrine systems, and its effects on the developing
breast involve delayed proliferation and differentiation of the mammary
gland, as well as an elongation of the window of sensitivity to potential
carcinogens. Implications of these new findings suggest that causes
of endocrine-related cancers or susceptibility to cancer may be a result
of developmental exposures rather than exposures existing at or near the
time of tumor detection. (Birnbaum et al, 2003)
Study #12
-
A glioma case [brain cancer] was associated with dioxin exposure
The vital status of 61 employees of a chemical company who were exposed
to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (1746016) was reviewed.
Job classifications were categorized into high and low potential exposure
to facilitate epidemiologic research. Production employees working in the
area of highest TCDD contamination and those engaged in sampling operations
as well as maintenance personnel assigned to production equipment were
categorized as high potential. Production personnel working away from areas
of highest contamination and those maintenance employees not directly involved
with production equipment were considered low exposure. Sixty one employees,
age ranging from 20 to 64 years were chosen and vital statistics for all
were determined through December 31, 1978. Expected numbers of deaths were
calculated from cause specific/age specific mortality rates for the U.S.
white male population. Severity of acne like lesions observed among 49
of the 61 patients ranged from questionable to severe. Acnegenic responses
were observed in 30 of 34 persons in the high exposure group and 14 of
16 in the low exposure group. Four deaths, one due to cardiovascular disease
and three due to malignant neoplasms, were observed compared to the 7.8
expected. The neoplasms included an adenocarcinoma, a fibrosarcoma, and
a glioma [brain cancer]. The authors conclude that although TCDD
exposure may be sufficient to produce chloracne it does not increase overall
mortality or cardiovascular death. Because no single type of tumor was
predominant, dioxin cannot be considered a potent human carcinogen with
organ or tissue specificity. [Note: this is a very small sample size.]
(Cook et al, 1980)
Study #13
-
alteration of cellular redox balance may mediate the TCDD-induced inhibition
of proliferation in human neuronal cells.
Oxidative stress has been known to be involved in the mechanism of toxic
effects of various agents on many cellular systems. In this study we investigated
the role of reactive oxygen species (ROS) in 2,3,7,8-tetrachlorodibenzo-p-dioxin
(TCDD)-induced neuronal cell toxicity using SK-N-SH human neuroblastoma
cells. TCDD inhibited proliferation of the cells in a dose-dependent manner,
which was revealed by MTT staining, counting of cells stained with trypan
blue and [3H]thymidine uptake assay. TCDD also suppressed the basal generation
of ROS in a time- and concentration-dependent manner assessed by 2',7'-dichlorofluorescein
fluorescence. In addition, TCDD induced a dose-dependent inhibition of
lipid peroxidation, a biomarker of oxidative stress, whereas it significantly
increased the level of glutathione (GSH), an intracellular free radical
scavenger in the cells. Moreover, TCDD altered the activities of major
antioxidant enzymes; increase in superoxide dismutase (SOD) and catalase,
but decrease in glutathione peroxidase (GSH-Px) and glutathione reductase
(GSH-Red). Pretreatment with L-buthionine-S,R-sulfoximine (BSO, 50 microM),
an inhibitor of GSH synthesis, significantly prevented the TCDD-induced
reduction in lipid peroxidation and cell proliferation. Interestingly,
exogenous application of an oxidant, H2O2 (50 microM) markedly restored
the inhibited cell proliferation induced by TCDD. Taken together, these
results suggest that alteration of cellular redox balance may mediate
the TCDD-induced inhibition of proliferation in human neuronal cells.
(Lee et al, 2002)
Upcoming Studies
CANTOR K. Cancer Risk and Exposures to Drinking Water Contaminants
and Other Environmental. Crisp Data Base National Institutes of Health.
Author Address: DCE, NIH
-
Study will examine links between brain cancer and chlorinated hydrocarbons
[such as PCBs and dioxins]
Risk factors for cancer from the ambient environment are studied to identify
specific chemicals and classes of contaminants, to investigate mechanisms
of action , and to estimate the contribution of environmental factors to
cancer in the general population. Case-control studies are conducted on
non-Hodgkin's lymphoma and cancers of the lung, bladder, colon,
rectum, stomach, esophagus, brain, pancreas, and kidney. Exposures
include drinking water contaminants, especially disinfection byproducts
and arsenic; airborne radon in homes; and body burdens of chlorinated
hydrocarbons from past environmental or dietary exposures. Related
case-control studies in Iowa showed excess risks for rectal cancer in both
sexes and bladder and brain cancers among men after long-term consumption
of disinfection byproducts in drinking water. The risk of brain cancer
after such exposures is being further investigated in the upper midwest.
We earlier found an association between PCBs in stored serum and subsequent
risk of non-Hodgkin's lymphoma. However, further analyses show no association
with several other organochlorines. Studies in Taiwan and elsewhere have
described a high risk for bladder and other cancers after exposure to arsenic
in drinking water supplies at levels several times the maximum contaminant
limit. A case-control study in Utah is evaluating bladder risk at lower
levels of arsenic that are more common in the U.S. A case-control study
of lung cancer and residential radon among Missouri women is unique because
it used a novel radon detector which integrates residential radon exposure
over the past 30 years (CR-39 detector). A significant excess lung cancer
risk was observed with increasing radon concentrations when measure by
the CR-39 detector but not when measured by standard radon dosimetry. We
have now completed the field phase of a study to evaluate the CR-39 detector
in Minnesota and Helsinki, Finland, laboratory analysis of the detectors
are planned for the next several months, with statistical analysis of the
data following. A retrospective cohort study of licensed radio amateurs,
including an occupational component, is evaluating patterns of mortality
that may be related to hobby or workplace exposures. Several activities
are developing new approaches, and improving existing methods, of exposure
assessment in studies of general environmental exposures. These are required
to better estimate risk and to detect the relatively small increases in
risk often encountered in such studies. Databases of water contaminants,
gathered for routine monitoring purposes, are being used to estimate past
exposures to subjects in case-control studies.extramural collaborators:
M. Bates, Ph.D., Communicable Disease Centre, Proirua, New Zealand J. Brock,
Ph.D., M. Lynberg, Ph.D., and L. Needham. Ph.D., CDC, Atlanta, GAJ. Cerhan,
Ph.D., May o Clinic, Rochester, MNM. Karagas, Ph.D., Univ. New Hampshire
C. Lynch, M.D., Uni v. of Iowa, Iowa City, IAJ. Nuckols, Ph.D. and J. Reif,
Ph.D., Colorado State Un iv., Ft. Collins, COA. Smith, M.D., UC Berkeley,
CAC. Wesseling, M.D. and P. Monge, M.D., National Univ., Heredia, Costa
Rica
Studies Without Abstracts
SAMUELS SW. THE MANAGEMENT OF POPULATIONS AT HIGH RISK IN THE
CHEMICAL INDUSTRY. Source: SELIKOFF, I. J. AND E. C. HAMMOND (ED.).
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, VOL. 381. BRAIN TUMORS IN THE
CHEMICAL INDUSTRY; WORKSHOP, NEW YORK, N.Y., USA, OCT. 27-28, 1980. XI+364P.
NEW YORK ACADEMY OF SCIENCES: NEW YORK, N.Y., USA. ILLUS. PAPER. ISBN 0-89766-152-4(PAPER);
ISBN 0-89766-151-6(CLOTH).; 0 (0). 1982. P328-343. Keywords include:
DIOXIN,
CARCINOGEN, BRAIN TUMOR, GENETIC FACTOR
Go to:
|