Slide 1:

Long Island Breast Cancer Study
Deborah M. Winn, Ph.D.
National Cancer Institute
February 2003

Slide 2:

Outline

• Long Island Breast Cancer Case Control Study (Marilie Gammon, PI)
• Broader picture of understanding the effects of environmental factors on breast cancer risk

Slide 3:

This slide shows a color-coded map of New York State showing variations in breast cancer incidence by zip code for 1993-1997. The map is by the New York State Department of Health.

Slide 4:

Public Law 103-43, June 10, 1993

• The Director of the National Cancer Institute in collaboration with the Director of the National Institute of Environmental Health Sciences, shall conduct a case-control study to assess biological markers of environmental and other potential risk factors contributing to the incidence of breast cancer in:
  • the Counties of Nassau and Suffolk, in the State of New York, and
  • 2 other counties with high rates (one in NY and one Connecticut)

Slide 5:

Public Law 103-43, GIS Requirement

• Certain elements of the study … shall include the use of a geographic system to evaluate the current and past exposure of individuals, including direct monitoring and cumulative estimates of exposure, to:
  1. contaminated drinking water
  2. sources of indoor and ambient air pollution, including emissions from aircraft
  3. electromagnetic fields
  4. pesticides, and other toxic chemicals
  5. hazardous and municipal waste
  6. other factors as appropriate.

Slide 6:

Principal Investigator and Team Members

• Marilie Gammon
  University of North Carolina
• Regina Santella
  Columbia University, New York, NY
• Mary Wolff
  Mount Sinai School of Medicine, New York, NY
• And many, many other collaborators and team members

Slide 7:

Study Population

• 1508 women newly diagnosed with breast cancer from New York cancer registry
• 1556 "population-based" control women without breast cancer from Random-Digit-Dialing and Medicare rosters

Slide 8:

Data Collection Protocol

• Women interviewed in homes about socio-demographics, reproductive history, diet, use of pesticides, medical history, use of hormones, family history of cancer, body size changes over lifetime, physical activity
• Women provided blood and urine samples
• Dust, tap water, and soil sampling

Slide 9:

Community Participation in the LI Study

• Town meetings held with community
• Served as Advisors on the case-control study and the Project as a whole
• Cancer Information Service outreach office on LI
• Advocates participated in peer-review of grants
• Continued participation of PI and NCI in LI network

Slide 10:

Findings: Most Established Risk Factors Confirmed (Magnitude of Increased Risk)

• Excess risk associated with
  • Increasing age
  • Family history of breast cancer
  • First birth at late age (>28 years)
  • Never having given birth
  • Higher income
• No excess risk for
  • Early age at menarche
  • Higher education attainment

Slide 11:

Hypotheses: To Determine If . . .

• Organochlorines and polycyclic aromatic hydrocarbons are associated with an increased risk of breast cancer among women in Long Island

Slide 12:

Organochlorines

• Included pesticides - DDT, DDE (a metabolite of DDT), chlordane, dieldrin and
• Polychlorinated biphenyls: chemicals found in coolants and lubricants in transformers, capacitors and other electrical equipment

Slide 13:

Polycylic Aromatic Hydrocarbons (PAHs)

• Caused by incomplete combustion of chemicals including:
  • Diesel fuel
  • Cigarette smoke
  • Vehicle exhaust
  • Smoked/grilled foods

Slide 14:

Why Study These Chemicals?

• Still ubiquitous in environment even though many of these compounds are no longer used
  • Measurable levels in biological fluids in many Americans
  • Persist in body for long time periods Previous Link to Cancer
  • DDT and related metabolites cause liver cancer in rats

Slide 15:

• DDT and PCBs have estrogenic activity in human tissues
• Estrogen is thought to be one of most important determinants of breast cancer
• PAHs cause breast cancer in rodents

Slide 16:

• Organochlorines
  • Were measured in blood
  • Blood levels correspond well to levels in tissues where organochlorines are stored (fat tissues)
  • Current levels now reflect cumulative levels throughout life

Slide 17:

A table shows the Odds Ratios for Breast Cancer according to blood levels of DDE (DDT metabolite). (Controlled for age, race, history of infertility problems, history of benign disease.) Data are shown comparing risk according to quartile of DDE among study participants. The odds ratios are:

• For women in the lowest quartile, 1.0
• For women in the second to lowest quartile, 0.88
• For women in the middle quartile, 0.94
• For women in the fourth quartile, 0.92
• For women in the highest quartile, 1.2

Slide 18:

More Findings

• No dose response relationship
• No increased risk associated with organochlorines among women who
  • Had not breastfed
  • Were overweight
  • Were post-menopausal
  • Long term residents of LI
  • Had invasive vs. in situ cancers
  • Had estrogen-receptor positive vs. negative tumor

Slide 19:

Bottom Line

• Findings do not support the hypothesis that organochlorines increase breast cancer risk among Long Island women

Slide 20:

Polycylic Aromatic Hydrocarbons

• PAH DNA-adducts measured in blood
• PAH adducts are metabolites of PAH that have bound to DNA
• Considered to reflect combination of exposure and capacity to repair DNA
• PAH adducts now reflect exposures perhaps within the past 3 year, but not entirely known

Slide 21:

This table shows the Odds Ratios for Breast Cancer for PAH-DNA adduct levels. (Controlled for age, race, history of infertility problems, season of blood donation, religion, parity, total number of months of lactation, body mass, first-degree family history of breast cancer, and age at first birth.). Data are shown comparing risk according to quartile of PAH-DNA adduct levels among study participants. The odds ratios are:

• For women in the lowest quartile, 1.0
• For women in the second to lowest quartile, 1.45
• For women in the third quartile, 1.48
• For women in the fourth quartile, 1.01
• For women in the highest quartile, 1.49

Slide 22:

Conclusions About PAHs

• No dose-response relationship
• No consistent association with two main sources of PAH: active or passive cigarette smoking or eating grilled and smoked foods
• These findings need to be replicated in other studies

Slide 23:

50% increased risk considered modest

• Smoking increases risk of lung cancer by 900-1000%
• A family history of breast cancer increases risk by 100-200%

Slide 24:

Case-Control Study Next Steps

• Do organochlorine compounds and lifestyle factors influence breast cancer survival?
• Are some common variations in certain genes associated with risk of breast cancer?
• Interaction of variants in genes and environmental contaminants and risk of breast cancer
• Electromagnetic fields and breast cancer

Slide 25:

Genes involved in

• Responses to oxidative stress
• Folate metabolism
• Estrogen biosynthesis and metabolism
  

Slide 26:

Relatively few well-established environmental causes of cancer in the general population

• Arsenic
• Radiation
• Environmental tobacco smoke

Slide 27:

Cancer case more likely to represent a cancer cluster if it involves

• One type of cancer (e.g., site, histology)
• A rare type of cancer
• A type of cancer in a group not usually affected by the cancer

Slide 28:

Long Island Geographic Information System

• Will provide researchers a new tool to investigate relationships between breast cancer and the environment in Suffolk and Nassau counties and to estimate exposures to environmental contaminants

Slide 29:

Long Island Geographic Information System

• Public will be able to use the website to examine patterns of environmental exposures and breast cancer

Slide 30:

LI GIS-H integrates

• Environmental and breast cancer databases
• Mapping capability
• Statistical tools

Slide 31:

This graphic illustrates how layers of data specific to a geographic area can be layered in a geographic information system. First layer shows an area with trees, a river, and buildings. Several horizontal layers are positioned above it to represent some of the different kinds of data that might be layered on top, for example, environmental, land use, engineering, and health data.

Slide 32:

Databases in Long Island GIS

• Breast cancer incidence (available from NY state registry)
• Breast cancer mortality
• Demographic
• Medical Facility
• Behavioral Surveys
• Air Quality
• Water Quality and Water Use
• Industrial Sites and Hazardous Materials
• Radioactive Sites or Materials

Slide 33:

Long Island GIS

• Available now to researchers with approved projects
• Public mapping features available soon

Slide 34:

Marin County, near San Francisco

• High breast cancer rates
• High level of community concern
• California county and state health departments, CA universities, NCI, NIEHS working to address these issues
• Major geographic information system under development (Peggy Reynolds, PI, California state health department)

Slide 35:

Some NCI methodological studies

• Statistical studies on cluster analysis
• Modeling of U.S. county breast cancer rates - efforts to determine how much of cancer incidence can be attributed to known risk factors that are available at the level of a county or other small geographic unit

Slide 36:

Interagency Task Force on Breast Cancer and the Environment

• NCI, NIEHS, CDC, and EPA partnership
• To develop guiding principles for responding to reports of high cancer incidences
• To develop approaches to assess the contribution of environmental exposures to breast cancer risks

Slide 37:

NIEHS/NCI RFA on Breast Cancer and the Environment

• Basic biological research - changes that occur in normal mammary gland throughout lifespan vs. exposure-induced changes
• Epidemiologic cohort studies to identify determinants of puberty in girls
• Community participation