# Presentation: 340040

## Long Island Breast Cancer Study

**Deborah M. Winn, Ph.D.**
**National Cancer Institute**

## 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

## 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)**

## 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:**
**contaminated drinking water **
**sources of indoor and ambient air pollution, including emissions from aircraft **
**electromagnetic fields **
**pesticides, and other toxic chemicals **
**hazardous and municipal waste**
**other factors as appropriate.**

## 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**

## 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**

## 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**

## 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**

## 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**

## Hypotheses:  To Determine If . . .

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

## 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**

## Polycylic Aromatic Hydrocarbons (PAHs)	

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

## 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**
**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**

## 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**

## Odds Ratio for Breast Cancer	

**Controlled for age, race, history of infertility problems, history of benign breast disease**

**Odds Ratio for Breast Cancer****	**

## 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**

## Bottom Line

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

## 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**

## Odds Ratios for Breast Cancer

- Controlled for age, race, history of infertility problems, season of blood donation, religion, parity, total # months of lactation, body mass, 1st degree family history of breast cancer, and age at first birth

**Odds Ratios for Breast Cancer**

## 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**

## 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%**

## 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**

## Genes involved in 

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

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

**Arsenic**
**Radiation**
**Environmental tobacco smoke**

## 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**

- CDC Center for Environmental Health Sciences

## 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**

## Long Island Geographic     Information System

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

## LI GIS-H integrates

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

## Long Island

**Long Island**
**Geographic**
**Information System**

**Notes:**
To understand the reasons behind these high breast cancer rates, the Long Island Breast Cancer Study Project was initiated.  It consists of more than 10 studies of breast cancer including human population (epidemiologic) studies, the establishment of a family breast and ovarian cancer registry, and laboratory research.  Earlier, you heard Dr. Ruby Senie talk about the cancer registry and Dr. Marilie Gammon describe a centerpiece of the project, a case control study she is leading to identify environmental factors that may be associated with breast cancer.  
The Project also includes the Long Island Geographic Information System.  Geographic information systems are powerful computer systems for mapping and analyzing the relationships over time and space between multiple layers of data.  The LI GIS will include more than 80 datasets containing information on a wide range of environmental and health data for Suffolk and Nassau county integrated into a single system.  It will also  have a researchers’ toolbox with the software and statistical tools needed to analyze data
The website, including public mapping facility, available early in 2002 

## 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**
**     **

## Long Island GIS

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

## 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)**

## 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**

## 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**

## 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**