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April 7, 1994
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The Northeast/Mid-Atlantic Study:
Environmental Factors and Breast Cancer in High-Risk Areas

The National Cancer Institute (NCI), in collaboration with the National Institute of Environmental Health Sciences (NIEHS), is currently funding six studies involving environmental exposures and breast cancer risk in the Northeast and mid-Atlantic regions of the United States. Collectively these six studies are known as the Northeast/Mid-Atlantic Study (NE/MA).

The NE/MA was initially mandated by Congress in the Cancer Registries Act in 1992. Language in the appropriation for fiscal year 1994 gave NCI the discretion to proceed or not to proceed with the study, based on its scientific merit. In September 1993, NCI awarded six grants for the 4-year study, which is budgeted at $6 million.

Geographic variation in age-adjusted breast cancer incidence and mortality rates has been well documented. Higher rates of breast cancer have been described for much of the Northeast, many mid-Atlantic states, and some Midwestern states. Nine states-Connecticut, Delaware, Maryland, Massachusetts, New Hampshire, New Jersey, New York, Rhode Island, and Vermont-and the District of Columbia are included in NE/MA. All have breast cancer mortality rates above the national average. Eight states are ranked in the top 10 with respect to breast cancer mortality rates for the years 1986 through 1990.

To some extent, variation in breast cancer incidence and mortality rates may be due to differences in population distribution; there may be more women with more risk factors in areas with higher rates. Commonly cited risk factors are a family history of breast cancer, early menses, late menopause, late age at first childbirth or no children, and some dietary and lifestyle factors.

Because only about 30 percent of breast cancer cases can be attributed to known risk factors, other factors, such as environmental exposures, also may contribute to these geographic variations. Possible factors include pesticides, automobile exhaust, landfills, water contaminants, electromagnetic fields, and heterocyclic amines (found in cooked meats).

Current biologic data relating environmental pollutant exposures to breast cancer risk are sparse. A few studies have found an association between increased levels of DDE in breast tissue and increased breast cancer risk; research also has indicated a risk associated with exposure to polychlorinated biphenyls (PCBs). However, other results have not shown associations between these chemicals and breast cancer.

The NE/MA's purpose is to examine the roles of various environmental exposures along with other possible risk factors to better understand the causes of breast cancer in areas of high incidence and mortality.

The studies that make up NE/MA are not the same studies that will comprise the Long Island Breast Cancer Study Project (LIBCSP). The LIBCSP is under way to examine environmental exposures and other potential risk factors contributing to the high breast cancer incidence rates in four U.S. counties, two of which are Nassau and Suffolk counties on Long Island. (The other two are Tolland County, Connecticut, and Schoharie County, New York.)

While both NE/MA and LIBCSP are funded by NCI, the projects are funded separately. NE/MA-funded investigators may apply for supplemental funding to participate in LIBCSP and bring their expertise to both projects.

Kathy J. Helzlsouer, M.D., Johns Hopkins School of Hygiene and Public Health
Environmental Factors and Breast Cancer Risk in Maryland

Using serum previously collected from Maryland residents, Helzlsouer and colleagues will determine organochlorine concentrations in 341 women who have developed breast cancer and compare the results with 341 controls. They also will analyze the serum for antioxidant nutrients (antioxidants are thought to be protective against cancer) and examine relationships among the nutrients, organochlorines, and risk of breast cancer.

The researchers also will characterize a specific gene that may be associated with susceptibility to carcinogens. They will determine whether this gene may influence serum organochlorine levels.

Tongzhang Zheng, M.D., Sc.D., Yale University School of Medicine
Organochlorine Compounds and Risk of Breast Cancer

Zheng and colleagues will conduct a case-control study to evaluate the relationship between organochlorine compound exposures and the risk of breast cancer in Connecticut.

A case-control study compares one group with a disease or condition (in this instance, breast cancer) with one or more groups that lack the disease or condition. Cases and controls are "matched" as closely as possible for factors (such as age, race, and sex) so that the factor to be studied is all that distinguishes the groups from one another.

Zheng's study will involve women 50- 79 – 200 with breast cancer (cases) and 200 with benign breast disease other than atypical hyperplasia (controls). Study participants will be recruited from patients diagnosed over a 3.25-year period at Yale-New Haven Hospital.

Researchers will examine the breast tissue of all the women for evidence and concentration of PCBs, DDT, DDE, and benzene hexachloride. They hypothesize that exposure to these OCPs increases a woman's risk of breast cancer.

Mary S. Wolff, Ph.D., Mount Sinai School of Medicine
Environmental and Genetic Determinants of Breast Cancer

In NE/MA, Wolff's group will conduct a case-control study involving women in the New York metropolitan area (New York City, Long Island, and New Jersey). This study will involve 210 women with breast cancer; 140 will be African American or Hispanic. Blood levels of DDE and PCBs in these women will be compared with levels in two control groups: 210 women who have had biopsies for benign breast disease other than atypical hyperplasia, and 210 women who were hospitalized for noncancer abdominal surgery. Organochlorine levels in fat also will be examined.

Wolff and colleagues also will characterize several carcinogen-metabolizing enzymes and genetic mutations that may be associated with effects of environmental exposures.

David Hunter, M.D., Sc.D., Brigham and Women's Hospital
Environmental Risk Factors and Breast Cancer in the Nurses' Health Study

These researchers have stored blood samples from 33,000 of the women in the Nurses' Health Study (NHS). From this group, they plan to identify 430 women who subsequently developed breast cancer (cases) and match them with 430 women who did not (controls). In all 860 samples, they will determine serum levels of vitamin D, PCBs, and DDE. They hypothesize that DDE and PCB levels will be higher and vitamin D levels lower in the women who developed breast cancer, compared with women who did not develop the disease.

In 1992, the researchers asked NHS participants about electric blanket use; they plan to analyze this type of exposure over the next 4 years. They also will examine regional variations in incidence and mortality among these women since 1976 and will assess the extent to which known risk factors explain these variations.

Jo L. Freudenheim, Ph.D., State University of New York at Buffalo
Environmental and Genetic Determinants of Breast Cancer

This study will examine the relationship of PCB and DDT levels to the risk of postmenopausal breast cancer. Using blood specimens collected as part of a previous study on breast cancer, levels of these compounds will be measured in 150 women with breast cancer and an equal number of women without the disease. Because there are a variety of PCBs with different biological effects, individual PCB compounds will be examined for their relationships to risk.

The interaction of PCB and DDT exposures with other risk factors, such as diet, medical and reproductive histories, and family history of cancer, also will be analyzed.

In addition, Freudenheim and colleagues will study the variability of genes that encode enzymes involved in the metabolism of carcinogens and other compounds. Different, naturally occurring forms of these genes may affect the rate of metabolism and detoxification in cells, potentially affecting cancer risk. Researchers will study associations among these genes, exposures to environmental contaminants, and other breast cancer risk factors.

Cristina M. Leske, M.D., Ph.D., State University of New York at Stony Brook
EMFs, OCPs, and Breast Cancer on Long Island, New York

Animal studies have raised the possibility that exposure to electromagnetic fields (EMF) of about 60 Hz might be associated with breast cancer by inhibiting secretion of the hormone melatonin from the pituitary gland. Reducing melatonin secretion may increase the ovarian secretion of estrogen, a well-established risk factor for breast cancer.

This case-control study, limited to women living on Long Island in the same residence for at least 15 years, will examine the possible roles of EMFs and other exposures in breast cancer development. EMF measurements will be made in and outside the houses of participants. Researchers will collect information also on other environmental exposures and known breast cancer risk factors.