BREAST CANCER

NIEHS scientists co-discovered the first breast cancer gene, BRCA1, and played a role in the multi-national discovery of BRCA2. Together, these genes may account for much familial breast cancer, the kind that clusters in some families. The genes may be involved in 5 to 10 percent of all breast cancer - and a higher percentage of early breast cancers (affecting women under 45). A test has been devised to identify women carrying the defective BRCA1 gene.

In another attack on this multi-faceted disease, NIEHS is studying a growth factor called transforming growth factor alpha that responds to the female hormone estrogen and may play a role in normal breast development - and could lead to new ways to detect breast cancer.

Grantees are studying the possible role of pesticides that may mimic some of the activity of estrogen. Institute scientists also collaborated on a study that showed that late first pregnancy and late menopause were associated with a higher risk of breast cancer, while women with four or more pregnancies had a significantly lower risk.

Environmental estrogens are a variety of synthetic chemicals and natural plant compounds that are thought to mimic the female hormone estrogen. They may act like estrogens or may block the natural hormone.

The body's estrogen controls the growth of cells by attaching to proteins called estrogen receptors throughout the body. Many environmental estrogens can attach to these same proteins, fooling the body or tissues by giving them an inappropriate "estrogen" signal. These compounds are found all around us. We eat them, drink them, breathe them and use them at work, at home and in the garden. They include pesticides such as the now-banned DDT; kepone, polychlorinated biphenyls (PCBs), natural plant products in our diet, and the drug DES, which was widely used for more than 20 years beginning in the 1940s to prevent spontaneous abortions in women. In 1971, researchers showed that daughters of women who took DES had a high rate of a rare form of cervicovaginal cancer. DES' common use as a growth promoter in cattle also was banned by the Food and Drug Administration in the 1970s.

NIEHS is supporting and conducting studies of environmental estrogen exposures, including a testing of the blood and urine of a representative group of Americans to determine how much of these chemicals are accumulating in the body . There is a possibility they might play a role in diseases such as cancers of the breast, uterus and ovaries; endometriosis and uterine fibroids. There is also a possibility that some of these estrogen-like substances, such as the ones occurring naturally in vegetables, may be beneficial.

ENDOMETRIOSIS

is a condition which occurs when endometrial tissue, the tissue that lines the uterus and is shed during menstruation, grows outside the uterus. When this abnormal growth occurs, painful implants can develop, most commonly on the ovaries, the fallopian tubes and the ligaments that support the uterus. Other possible sites for endometrial growths are the bladder, bowel and reproductive organs. Endometriosis affects an estimated 10% - 15% of premenopausal women. The cause of it is unknown. Many of the risk factors for this disease are related to estrogen exposure. Thus, environmental estrogens may contribute to the development of endometriosis in susceptible individuals.

UTERINE FIBROIDS

The most common tumors in women are benign (non-malignant) uterine fibroids, or leiomyomas. These tumors are present in 20% - 30% of women over age 30; uterine fibroids are more common in African-American women.

Fibroids can cause significant pain and discomfort and are associated with reproductive problems. They are the leading reason for hysterectomies - major operations in which the uterus is surgically removed, either through the abdominal wall or the reproductive organs.

NIEHS epidemiologists are conducting a study of uterine fibroids in black and white women in their late-reproductive years who are members of the George Washington University Health Plan in Washington, D.C.

OSTEOPOROSIS

is a debilitating condition characterized by fragility of the bone. It sometimes occurs in men but is generally found in postmenopausal women. Cadmium, lead and possibly other heavy metals found in the environment may be significant factors in developing this disease. NIEHS-supported research has shown that cadmium exposure results in increased loss of bone mineral in mice whose ovaries have been removed. The bone loss appears to occur from a direct action of cadmium on bone, not through an indirect effect on kidney reabsorption of calcium. Thus, cadmium exposure may be a significant factor contributing to osteoporosis in older women. Continued efforts to study the basic physiology of bone metabolism as well as the mechanisms of heavy metal toxicity in bone tissue should provide insight into the disease mechanisms of osteoporosis.

Other NIEHS-supported studies are investigating the health consequences of lead released into the blood stream and soft tissue due to osteoporosis. One health effect that has been identified is an increased risk for hypertension. Some of these studies are using lead as a marker to develop hormonal therapies to prevent bone reabsorption

The body produces antibodies that fight foreign proteins known as antigens. In lupus, the antibodies mistake the body's own cells as foreign and attack them. The disease may range from mild to severe and is characterized by periods of flareups and remissions. Lupus may cause weight loss, fever, fatigue, aching, and weakness and may involve different organ systems such as the central nervous system, the heart, lungs, kidneys, muscles, and joints. A gene on chromosome 1 has been linked with susceptibility to lupus in Caucasians, Asians, and African Americans.

Exposures to various chemicals such as pharmaceuticals and solvents have been linked to autoimmune diseases. For example, exposure to hydrazine, an industrial chemical, or tartrazine, a food additive, is associated with lupus. And scleroderma has been associated with workplace exposure to vinyl chloride and silica dust.

Women have particular environmental diseases related to their gender, as well as sharing other environment-related diseases with men and children.

While some environmental estrogens may cause harm, there is a possibility some may reduce risks . . .

Fibroids, the leading reason for hysterectomies, are being studied in black and white women in a Washington health plan . . .

• Pregnancy related health and environmental Exposure Issues