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EDRI Federal Project Inventory:
62951-03 Environmental and Genetic Determinants of Breast Cancer
- Sponsor Organization: NIH/NCI
- Project Title: 62951-03 ENVIRONMENTAL AND GENETIC DETERMINANTS OF BREAST CANCER
- Project Focus: HUMAN HEALTH EFFECTS
- Description: Preliminary research conducted by our group has found a powerful
association between female breast cancer andbody burden of DDE, the
principal metabolite of DDT. This association is stronger (RR equals
approximately 4) thanthat between breast cancer and obesity (RR less
than 1.5) or delayed child-bearing (RR less than 2). Lower,
butelevated, risks were found with PCBs. These exposures are
preventable. We will investigate breast cancer risk amongwomen in the
New York metropolitan area, including minorities, with respect to
environmental factors, carcinogenmetabolizing enzymes, and oncogenes.
Levels of organochlorines (DDE and PCB) in blood serum will be
comparedbetween breast cancer cases and two control groups. The
relationship of breast cancer to genetic polymorphisms incarcinogen
metabolizing genes (CYP1A1, CYP1A2, CYP2E1, GST) will be determined.
Interactions of genotype withenvironmental exposures and carcinogen
metabolizing genes will be investigated with respect to risk of breast
cancer. Expression of p53, c-myc and erbB-2 in relation to
organochlorine exposure and carcinogen-metabolizing genotype willbe
assessed. Estrogen receptor and epidermal growth factor receptor
levels will be determined in an effort to determinerelationships
between breast cancer risk and environmental exposures, cytochrome
P450 metabolism and oncogeneexpression. In order to verify the
validity of blood serum levels as an indicator of body burden,
organochlorine levels inmammary or upper abdominal adipose will be
compared with levels in blood serum for a subset of each case and
controlgroup. A case-control study has been designed to compare 210
patient cases of invasive cancer, including 140 (66)minority women,
with 2 control groups. The control groups comprise 210 patients that
required biopsy for non-hyperplastic benign breast disease and 210
women hospitalized for elective abdominal surgery (noncancer). Cases
andcontrols will be frequency-matched on age and race. Residence
status in New York City, Long Island, and New Jerseywill be a variable
in the analysis. Patients will be drawn from over 1000 breast
biopsies seen annually in the MountSinai Breast Service. In addition
to the effect variables needed to assess the hypotheses, data will
include potentialconfounders for both breast cancer and organochlorine
environmental exposures. Statistical analyses will be designed tomodel
cancer risk associated with environmental exposures and their
interactions with genetic and biologic markers.
- References:
- Category: MEASUREMENTS
- Subcategory: EXPOSURE AND RISK MODELS
- Keywords for Experimental System/Species: HUMAN, FIELD STUDY
- Keywords for Experimental Endpoints: CARCINOGENESIS, FEMALE, EXPOSURE MONITORING, CYTOCHROME P450
- Chemical Agents: PCBs, DDT
- Performing Institution: MOUNT SINAI SCHOOL OF MEDICINE
- Contact: CONTACT PERSON: ELAINE C. LEE; BUILDING 31; 11A21, NATIONAL CANCER
INSTITUTE, NIH,BETHESDA, MD 20892-2590; 301- 496-5515;
LEEE@OD.NCI.NIH.GOV
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