Environmental Factors and Breast Cancer Risk by NIHhealth


									Environmental Factors and Breast Cancer Risk
For millions of women whose lives
have been affected by breast cancer,
the 1994 discovery of the first breast
cancer gene by researchers from the
National Institute of Environmental
Health Sciences (NIEHS) was a
welcome sign of progress in the
fight against this dreaded disease.
While this discovery and others
like it are certainly encouraging,
statistics tell us that breast cancer
is still a major health concern for
women everywhere. According to
the American Cancer Society, more        woman’s chances of developing          interplay between genetics and the
women in the United States are           breast cancer, they do not yet know    environment in the development
living with breast cancer than           how these risk factors work together   of this disease. The Sister Study
with any other non-skin cancer.          to cause normal cells to become        is enrolling 50,000 healthy sisters
Breast cancer is the leading cause       cancerous. Most experts agree          of women diagnosed with breast
of cancer death for U.S. women           that breast cancer is caused by a      cancer from across the country.
between the ages of 20 and 59,           combination of genetic, hormonal       Women of all backgrounds and
and the leading cause of cancer          and environmental factors.             ethnic groups who are between
death for women worldwide.                                                      35 and 74 years of age are
                                                                                encouraged to participate.
Gene-Environment Interactions
                                                                                Sisters of breast cancer patients
For years, NIEHS has played a                                                   share many of the same genes,
leadership role in funding and
conducting studies on the ways                                                  are more likely to develop the
in which environmental exposures                                                disease themselves, and are likely
increase breast cancer risk. These                                              to have been exposed to the same
studies have included the use of                                                environmental risk factors during
animal models to understand the
role of environmental agents in the
                                                                                early childhood.
initiation and progression of cancer,                                           The researchers will compare the
as well as research on chemical risk     The Sister Study                       genetic profiles and environmental
factors and genetic susceptibility       As new research continues to           exposures of sisters who don’t
in human populations.                    unravel the mysteries surrounding      develop breast cancer with those
                                         the causes of breast cancer, NIEHS     who do become cancer patients
Although scientists have identified
                                         scientists are laying the groundwork   in order to uncover clues that
many risk factors that increase a
                                         for a landmark study of the possible   may ultimately eliminate this
                                                                                dreaded disease.

PO BOX 12233
Research Triangle Park, NC 27709
Phone: 919. 541.1919
                                                                                                            January 2007
Study volunteers provide                defective, can predispose a woman
researchers with samples of their       to hereditary breast and ovarian
blood, urine, toenail clippings and     cancer.1 Diagnostic tests can
household dust, each of which will      now identify women who have
be analyzed for pesticides, heavy       inherited defective copies of the
metals and other environmental          gene and are more likely to
chemicals that may be linked to         develop breast cancer.
breast cancer development. The
                                        Although genetics is an important
researchers will also look for
                                        contributor to breast cancer
specific gene variations that may
                                        development, twin studies
predispose a woman to the effects
                                        conducted by scientists in
of cancer-causing agents. Women
                                        Scandinavia showed that inherited
enrolled in the study also fill out
                                        factors accounted for only 27
detailed questionnaires about their
                                        percent of breast cancer risk.2
health history, past environmental
                                        Another study shows that the
exposures, and lifestyle. The
                                        breast cancer rates of descendants
participants will be given yearly
                                        of Japanese women who migrate
follow-up questionnaires to account
                                        to the United States become
for changes in their health status or
                                        similar to the higher breast cancer
environmental exposures.
                                        rates of Western women within            solvents and flame retardants, and
                                        one or two generations.3 These           a variety of chemicals used in the
                                        findings point to the significant        manufacturing of dyes, rubber,
                                        role played by environmental             vinyl, and polyurethane foams.
                                        factors in determining breast
                                        cancer susceptibility.
                                                                                 Breast Cancer and Environment
                                                                                 Research Centers
                                        Cancer-Causing Chemicals
                                                                                 Recent studies suggest that
                                        Scientists are particularly interested   exposures to cancer-causing
                                        in whether exposure to naturally         chemicals during development
                                        occurring and synthetic chemicals        may affect breast cancer risk later
                                        may influence breast cancer              in life. During early childhood
                                        risk. This includes exposure to          and adolescence, the developing
Discovery of the BRCA1 Gene             chemicals in the air we breathe,         breast tissue is composed of
                                        the food and beverages we                rapidly dividing cells. These
The impact of family history on         consume, and the chemicals that          immature breast cells are much
breast cancer risk suggests that        come in contact with our skin.           more susceptible to the damaging
genetic factors play an important       The National Toxicology Program,         effects of environmental chemicals.
role in breast cancer susceptibility.   an interagency testing program           Results from animal studies have
Researchers are just beginning          headquartered at the NIEHS, has          shown that early exposures to some
to understand how changes in            listed more than 40 chemicals in         chemicals may keep the mammary
certain genes can impair the gene’s     its Report on Carcinogens because        gland in an immature state for
ability to control cell growth and      they were found to cause tumors in       longer periods, increasing its
division, causing normal breast         laboratory animals. These include        susceptibility to chemical insult.
cells to become cancerous. In 1994,     pharmaceutical products such
NIEHS scientists collaborated with      as diethylstilbestrol, a synthetic       In an effort to uncover the links
researchers from the University of      form of estrogen that was used           between early environmental
Utah Medical Center to identify         to prevent miscarriages, chemical        exposures and cancer risk, NIEHS
a gene called BRCA1 that, when                                                   is partnering with the National
Cancer Institute to fund four Breast     and concerns of the breast cancer       Researchers at Fox Chase Cancer
Cancer and the Environment               advocacy community are heard            Center are exposing rats to the
Research Centers (see text box on last   and that the research findings are      plasticizers bisphenol A and butyl
page). The purpose of the centers        disseminated to the public.             benzyl phthalate at different
is to investigate the impact of                                                  times during mammary gland
                                         Scientists at the University of
prenatal and childhood exposures                                                 development. The investigators
                                         California, San Francisco have
on mammary gland development,                                                    are finding that these endocrine
                                         found that GATA-3, a gene that
and the potential of these exposures                                             disrupting compounds activate
                                         guides the development of stem
to alter the risk of breast cancer                                               different genes depending on the
                                         cells into mature mammary cells, is
in later adulthood. The research                                                 time of the exposure and the age
                                         also required for mammary
findings will be developed into                                                  at which the rats are examined.
                                         cells to remain in the mature state
public health messages designed
                                         during adulthood. Experiments in        Experiments conducted by
to educate young women who are
                                         mice reveal that without the critical   scientists at Michigan State
at risk for breast cancer about the
                                         gene, mature mammary cells revert       University are focusing on the role
roles of environmental agents in
                                         to a less specialized state that        of progesterone, a hormone
breast cancer development, and
                                         is characteristic of                                     secreted in the
the importance of reducing their
                                         aggressive breast                                        second half of
exposures to these agents.
                                         cancer.4 The results                                     the menstrual cycle,
Initiated in 2003, the centers have      suggest that a                                           in breast cancer
worked in close collaboration on         defective GATA-3                                         development.
two different approaches to the          gene may play a                                          The researchers
early exposure hypothesis. One           significant role in                                      are using animal
approach will use basic science          the development                                          models to study
techniques in laboratory animals         of certain kinds                                         the influence of
and cell cultures, while the other       of breast cancer.                                        progesterone on
will use epidemiologic studies                                                                    mammary gland
                                         At the University
in human populations. Each                                                                        cell growth and
                                         of Cincinnati Center,
center has a community outreach                                                                   maturation. The
                                         investigators are
component to ensure that the views                                                                responses they
                                         studying the effect
                                                                                 get from the animal data may
                                         of childhood diet and obesity on
                                                                                 shed new light on the role
                                         the maturation of the developing
                                                                                 of this female hormone in
                                         mammary gland and subsequent
                                                                                 human breast development.
                                         risk of cancer later in life. Their
                                         preliminary work with animals
                                                                                 Chemical Exposures
                                         shows that treatment with soy           in Human Populations
                                         and other estrogen-like plant
                                         compounds may influence                 In some regions of the country,
                                         not only the rate of mammary            where there is an unusually
                                         gland maturation, but also the          high incidence of breast cancer,
                                         susceptibility of the gland to          environmental factors have been
                                         chemical carcinogens. They are          targeted as a possible cause for
                                         also testing the hypothesis that        this increase. During the 1990’s,
                                         pre-pubertal obesity in young           the NIEHS and the National
                                         girls may lead to earlier first         Cancer Institute co-funded the
                                         menstruation and increased              Long Island Breast Cancer Study
                                         susceptibility of the mammary           Project, one of the largest and
                                         gland to carcinogenic insults.          most comprehensive studies ever
                                                                                 conducted on the environmental
                                                              Northeast Mid-Atlantic Breast                                by suppressing the levels of a key
                                                              Cancer Program, included data                                hormone called melatonin. The
                                                              from five separate studies – two                             study also showed that extended
                                                              conducted in New York, one in                                periods of darkness greatly slowed
                                                              Connecticut, another in Maryland,                            the growth of these tumors.(8)
                                                              and the Nurses’ Health Study,                                The results provide a possible
                                                              a nationwide investigation into                              explanation for the higher rate
                                                              the risk factors for major chronic                           of breast cancer in female night
causes of breast cancer, to                                   diseases in women. In each of the                            shift workers and the epidemic
investigate the high rate of breast                           studies, blood was drawn from                                rise in breast cancer incidence in
cancer on Long Island in New York.                            both breast cancer patients and                              industrialized countries like the
                                                              healthy controls, and tested for                             United States.
The study scientists focused their                            DDT, DDE, and polychlorinated
investigation on three widespread                                                                                          While these findings are
                                                              biphenyls. A combined analysis
pollutants to which many of                                                                                                encouraging, more research
                                                              of the data from the five studies
the Long Island residents had                                                                                              is needed to pinpoint the
                                                              revealed no significant association
been exposed – organochlorine                                                                                              environmental and genetic factors
                                                              between the subjects’ serum
pesticides, including DDT and its                                                                                          that determine breast cancer
                                                              concentrations of these compounds
metabolite DDE, polychlorinated                                                                                            susceptibility. Once scientists
                                                              and an increased risk of breast
biphenyls, toxic compounds used                                                                                            can identify the elements that
in electrical transformers, and                                                                                            are associated with cancer risk,
polycyclic aromatic hydrocarbons                                                                                           appropriate interventions and
(PAHs), a primary component of                                                                                             precautions can be designed
urban air pollution. Although there                                                                                        for those who are most likely
was some evidence of a modest                                                                                              to develop the disease.
increase in the risk of breast cancer
from PAH exposure, the researchers
did not identify any environmental                                                                                            NIEHS Breast Cancer and the
factors that could be responsible                                                                                             Environment Research Centers
for the high incidence of breast
cancer in the Long Island area.5                              Pursuing New Leads:                                             •	Fox	Chase	Cancer	Center,		
                                                              Artificial Light
In a separate study conducted on                                                                                              	 Philadelphia
Long Island women, researchers                                Results from a study conducted                                  •	University	of	California,		
at Stony Brook University found                               by NIEHS-funded researchers in                                  	 San	Francisco
no association between exposure                               New York are the first experimental
to electromagnetic fields from                                evidence that artificial light may                              •	Michigan	State	University,		
residential power use and breast                              play an important role in breast                                	 East	Lansing
cancer risk.6                                                 cancer development. The results                                 •	University	of	Cincinnati,		
                                                              show that nighttime exposure
A similar NIEHS-NCI funded                                                                                                    	 Cincinnati,	Ohio
                                                              to artificial light stimulated the
study of environmental exposures
                                                              growth of human breast tumors
and breast cancer incidence, the

1. Miki et al. (1994) A Strong Candidate for the Breast and Ovarian Cancer Susceptibility Gene BRCA1. Science 266(5182):66-71.
2. Lichtenstein et al. (2000) Environmental and Heritable Factors in the Causation of Cancer: Analyses of Cohorts of Twins From Sweden, Denmark and Finland.
   New England Journal Medicine 343(2):78-85.
3. Shimizu et al. (1991) Cancers of the Prostate and Breast Among Japanese and White Immigrants to Los Angeles County. British Journal Cancer 63:963-966.
4. Kouros-Mehr et al. (2006) GATA-3 Maintains the Differentiation of the Luminal Cell Fate in the Mammary Gland. Cell 127:1041-1055.
5. Gammon et al. (2002) Environmental Toxins and Breast Cancer on Long Island I: Polycyclic Aromatic Hydrocarbon DNA Adducts.
   Cancer Epidemiology Biomarkers Prev. 11:677-685.
6. Schoenfeld et. al. (2003) Electromagnetic Fields and Breast Cancer on Long Island: A Case-Control Study. American Journal Epidemiology 158(1):47-58.
7. Laden et al. (2001) 1,1-Dichloro-2,2-bis(p-chlorophenyl)ethylene and Polychlorinated Biphenyls and Breast Cancer: Combined Analysis of Five U.S. Studies.
   Journal National Cancer Institute 93(10):768-775.
8. Blask et al. (2005) Melatonin-Depleted Blood from Premenopausal Women Exposed to Light at Night Stimulates Growth of Human Breast Cancer Xenografts in Nude Rats.
   Cancer Research 65:11174-11184.

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