Breast Cancer and the Environment on Long Island
 |
Marilie D. Gammon, Ph.D., principal
investigator
Universtiy of North Carolina at Chapel Hill
Chapel Hill, N.C. |
The cornerstone of the LIBCSP is the Breast Cancer and the Environment
on Long Island Study, which was undertaken to determine whether certain
environmental contaminants increase risk of breast cancer among women
on Long Island. This investigation has been led by Dr. Marilie Gammon,
of the University of North Carolina (UNC) at Chapel Hill, and has been
a collaborative effort of New York City and Long Island researchers.
The primary aims were to determine if organochlorine pesticides, including
DDT, polychlorinated biphenyls (PCBs), dieldrin, and chlordane, and polycyclic
aromatic hydrocarbons (PAH), a ubiquitous pollutant caused by incomplete
combustion of various chemicals including diesel fuel and cigarette smoke,
are associated with risk for breast cancer among women on Long Island.
Dr. Gammon and colleagues reported the major findings from the study
in August 2002. They found that organochlorine compounds are not associated
with the elevated rates of breast cancer on Long Island. However, the
researchers said that it is possible that breast cancer risk in some individuals
may be associated with organochlorine exposures because of individual
differences in metabolism and ability to repair DNA damage, and they are
continuing to investigate these possibilities. The researchers also found
that exposure to PAHs was associated with a modest increased risk for
breast cancer.
Following is the UNC press release:
 |
August 6, 2002 |
Long Island Breast Cancer Study Project uncovers
small risk from hydrocarbons, not organochlorines
CHAPEL HILL -- Exposure to air-polluting polycyclic
aromatic hydrocarbons (PAHs) in the environment appears to elevate
women's risk of breast cancer by a modest 50 percent in Suffolk
and Nassau counties, N.Y., a new much-anticipated study indicates.
The Long Island Breast Cancer Study Project, one
of the largest and most comprehensive environmental epidemiologic
studies ever done on that cancer, uncovered no increased rate of
the illness among area women who might have been exposed to organochlorine
compounds.
"Starting with more than 3,000 women in this
federally mandated research, we looked at blood samples taken from
hundreds of new breast cancer patients and comparable women without
breast cancer who served as controls," said principal investigator
Dr. Marilie D. Gammon.
Gammon is associate professor of epidemiology at
the University of North Carolina at Chapel Hill School of Public
Health.
In their work on polycyclic aromatic hydrocarbons,
which are known to cause mammary tumors in laboratory rats, researchers
focused on PAH-DNA "adducts" - chemicals attached to the
genetic material known as DNA, she said. PAHs are inhaled through
air pollution, including automobile and airplane exhausts and cigarette
smoke, and are ingested by eating selected foods, including grilled
and smoked foods. PAH-DNA adducts are evidence of exposure and suspected
evidence of tissue damage in humans.
Except for the possible 50 percent increase in
the risk of breast cancer associated with the highest levels of
hydrocarbon adducts, "there was no increasing elevation in
the risk of breast cancer with increasing adduct levels, nor was
there a positive association between adduct levels and two of the
main sources of PAHs," she said.
"Those are active or passive cigarette smoking
and consumption of grilled and smoked foods. Our data indicate that
PAH-DNA adduct formation may influence breast cancer development,
although the association does not appear to be dose dependent and
may have a threshold effect.
"These ambiguous findings shed some doubt
on a clear cause-and-effect association," Gammon said. "The
study team is continuing to investigate this issue on Long Island
through additional research focused on the possibility of individual
responses to environmental exposures."
In their research on organochlorines, including
the pesticide DDT, its metabolite DDE and industrial compounds known
as PCBs, the scientists found no evidence supporting an association
between those environmental toxins and heightened risk of breast
cancer, she said. Analyzing blood samples from 646 patients and
429 control subjects, they showed such factors as breastfeeding,
weight, menopausal status, length of residence on Long Island and
form of breast cancer made no difference. Nor was there any increase
in breast cancer associated with individual PCB variations, known
as congeners. Not excluded was the possibility that such chemicals
played an earlier, more subtle role in tumors.
"Recent research by other investigators suggests
that organochlroine compounds may be related to the type of breast
cancer that has clinical characteristics that are associated with
worse survival. This is an important issue that we are continuing
to investigate among the women in our study," Gammon said.
A report on the results appears in the August issue
of Cancer Epidemiology, Biomarkers & Prevention. Besides
Gammon, scientists involved include Drs. Regina M. Santella and
Alfred I. Neugut of the Mailman School of Public Health at Columbia
University, Mary S. Wolff of Mount Sinai School of Medicine and
24 other scientists from such institutions as Columbia, the State
University of New York at Stony Brook, Cornell Medical Center and
Long Island hospitals.
"The goal of this population-based, case-control
study was to determine whether breast cancer incidence in women
in these two counties was associated with exposures to environmental
contaminants," said Gammon, deputy director of UNC's Environmental
Health and Susceptibility Center and a UNC Lineberger Comprehensive
Cancer Center member. "What we observed did not support that
possibility strongly."
Because of circumstantial evidence, many experts
believe certain pollutants increase women's exposure to the hormone
estrogen, which boosts cell turnover so that it's harder for the
body to repair damage before cells replicate and pass the damage
to new cells, she said. Breast cancer victims are known to have
more estrogen in their blood on average than other women.
"We know too, for example, that if a woman's
ovaries, which produce estrogen, are removed before she is 35, her
risk of breast cancer drops by half," Gammon said. "Men,
who have little estrogen, rarely get breast cancer." The increase
in breast cancer risk associated with PAH was restricted to women
with breast tumors that were either estrogen receptor and progesterone
receptor positive or who were negative for both, she said. This
means the link was stronger for women with cancers that are considered
hormone sensitive. Why is unclear.
"Our findings with polycyclic aromatic hydrocarbons
suggest that women's individual responses to similar PAH exposures
might be more relevant to breast cancer development than the absolute
amount of PAH exposure," Gammon said. "A lot more work
needs to be done to sort out exactly what and how environmental
exposures may promote breast cancer."
The National Cancer Institute and the National
Institute of Environmental Health Sciences paid for the research,
which Congress mandated in 1993. The study came in response to concerns
by Long Island cancer activists that Nassau and Suffolk counties
showed disproportionately high breast cancer levels compared with
other parts of New York state.
|
In a third paper also published in August 2002, Dr. Gammon and colleagues
describe the full study population and research methods, and the established
risk factors for breast cancer found in the group. Many of the well-known
breast cancer risk factors were confirmed in the study. These risk factors
included increasing age, having a family history of breast cancer, having
a first child at a later age (age 28 or older in this study), never having
given birth to a child, and having higher income.
Background
For the population-based study, all women in Nassau and Suffolk counties
who were newly diagnosed with breast cancer during a one-year period beginning
August 1996 (cases) were invited to participate. A comparison group (controls)
of women who did not have breast cancer were randomly selected from the
two counties. Altogether about 1,500 cases and 1,500 controls participated.
Altogether, 1,508 women who were newly diagnosed with in situ or invasive
breast cancer, and a similar number of women who did not have cancer participated
in the study. (In situ breast cancer is early cancer that has not spread
to neighboring tissue.)
The study participants were asked to answer two questionnaires and to
donate blood and urine specimens. The main
questionnaire asked the women about their pregnancy and occupational
histories, residential history in Nassau and Suffolk counties, use of
pesticides in and around the home or farm, use of electrical appliances,
lifetime history of eating smoked or grilled foods, active and passive
cigarette smoking history, alcohol consumption, medical history, menstrual
history, use of hormones, family history of cancer, body size changes
by decade of life, lifetime participation in recreational physical activities,
and demographic characteristics, such as race/ethnicity. Women were also
asked to complete a food questionnaire.
A subset of the study population who had lived in their current homes
for 15 years or more was invited to participate in environmental sampling
of house dust, tap water, and yard soil. A random sample of white women
who had met the residency requirement were invited to participate. All
study participants who identified themselves as African American or black
and who met the residency requirement were invited to participate. Of
the total study population, 383 cases and 429 controls participated in
the home study.
Analyses of data from the urine samples for estrogen metabolites, of
the questionnaire data, and from the home study are on-going and are expected
to be reported in the next few years. (Estrogen metabolites are of interest
because differences in the way women metabolize estrogen may be related
to risk for breast cancer.)
Also as part of the LIBCSP, Dr. Gammon and colleagues are continuing
to follow the women with breast cancer who participated in the study
to determine whether organochlorine compounds (including DDT/DDE, PCBs),
PAH, and lifestyle factors influence survival of Long Island women diagnosed
with the disease. Dr. Gammon received a 4-year grant for this research
from NCI in August 2001.
Spin-off Studies, Opportunities to Collaborate
Numerous spin-off studies are underway using the population, data, or
specimens from the Breast Cancer and the Environment on Long Island Study.
These studies are funded by various organizations and are independent
of the LIBCSP. Researchers who are interested in conducting research using
the data and/or specimens from the study may contact Dr.
Gammon.
Some of the spin-off studies underway include:
- Dr. Gammon is examining p53 protein in tumor tissue. P53 is a gene
which normally regulates the cell cycle and protects the cell from damage
to its genome. Mutations, or changes, in this gene cause cells to develop
cancerous abnormalities. This p53 study is funded by the U.S. Department
of Defense (DOD).
- Habibul Ahsan, M.D., of Columbia University, New York, and colleagues
are examining whether certain common variations in the sequence of DNA
involved in the biosynthesis and metabolism of estrogen and environmental
carcinogens are associated with risk for breast cancer. This study is
funded by DOD, NCI, and the Cancer Research Foundation of America
- Regina Santella, Ph.D., also of Columbia University, and colleagues
are re-analyzing the PAH-DNA adducts from the Breast Cancer and the
Environment on Long Island Study using a different assay, in order to
learn more about the etiology of breast cancer. An assay is a laboratory
test to find and measure the amount of a specific substance. This study
is funded by DOD and NCI.
- Dr. Gammon and Dr. Santella are examining the role of variants in
genes involved in oxidative stress related to environmental contaminants.
Oxidative stress is a term used to describe a type of damage to the
body due to products derived from the metabolism of oxygen. This research
is funded by NCI.
- Rebecca Cleveland, of the University of North Carolina at Chapel Hill,
and Dr. Gammon are examining variants of insulin-like growth factor
(IGF-1) in relation to risk for breast cancer. IGF-1 is known to cause
proliferation of human breast cancer cells, and also to prevent the
body's clearing of old and damaged cells. This may cause increased growth
of tumor cells, in addition to accumulation of breast cells that have
mutated to cancerous forms. The study is funded by DOD.
- Geoffrey Kabat, Ph.D., a New York epidemiologist, and colleagues are
expanding on research begun in the Breast Cancer and the Environment
on Long Island Study to further study estrogen metabolites in urine
as potential markers for breast cancer risk. The researchers are using
biospecimens from women who are participating in the Metropolitan New
York Registry for Breast Cancer. The study is funded by the registry.
- Jia Chen, Ph.D., of Mt. Sinai School of Medicine, New York, and colleagues
are studying whether variations in genes involved in the metabolism
of folate are related to risk for breast cancer. Folate deficiency may
be associated with increased risk for breast cancer. The study is funded
by DOD.
Newsletters:
Issue 1 (Spring 1996) PDF
FORMAT
Issue 2 (Fall-Winter 1996)
PDF FORMAT
Issue 3 (Fall 1997 - Winter
1998) PDF FORMAT
Issue 4 (Winter - Spring 1999)
PDF FORMAT
Published
Reports
Funding / Timeline
|
