Scientists report in Nature Genetics (Oct. 1, 1995) that they have found
a specific alteration of the BRCA1 gene in approximately 1 percent of a group of Ashkenazi
Jews. Additional research will be needed to see if this alteration increases breast cancer
risk in those who have it.
1. What is breast cancer?
Breast cancer is a group of related diseases in which cells within the breast become
abnormal and divide without control or order, invading and damaging nearby tissues and
organs. When cancer cells break away from the original tumor and enter the bloodstream or
lymphatic system, breast cancer may spread and form secondary tumors (metastases) in other
parts of the body. The most common types of breast cancer arise in the lining of the ducts
or in the lobules of the breast.
2. What is the risk of developing breast cancer?
In the United States, a woman's lifetime risk of developing breast cancer is about 12
percent. An average woman's chances of getting breast cancer is about one in 200 by age
40, one in 50 by age 50, and one in 25 by age 60. In some families, where breast cancer
occurs in an inherited pattern, the risk is higher. About 5 to 10 percent of women with
breast cancer have a hereditary form of the disease. These women usually have a higher
risk of developing breast cancer at a younger age (before menopause), and they often have
multiple family members with the disease.
3. What are the risk factors for breast cancer?
By studying large numbers of women all over the world, researchers have found certain
risk factors that increase a woman's chance of developing breast cancer. Many women who
get breast cancer have none of the known risk factors, other than the risk that comes with
growing older. And, studies show that most women with known risk factors do not get breast
cancer. Some of the known risk factors are:
- Age. The risk of breast cancer increases as a woman gets older. Most breast
cancers occur in women over the age of 50; the risk is especially high for women over 60.
This disease is uncommon in women under the age of 35, except in some families with the
hereditary form of the disease.
- Family history. The risk of getting breast cancer increases for a woman whose
mother, sister, or daughter has had the disease. A woman's risk increases more if her
relative's breast cancer developed before menopause or if it affected both breasts.
- Personal history. The risk of breast cancer is greater than average in women who
have had a previous breast cancer; carcinoma in situ, an abnormality of breast
cells that is not considered cancer but has the potential to become an invasive cancer; or
atypical hyperplasia, a noncancerous condition in which breast tissue has certain
abnormal features.
Other risk factors for breast cancer include starting to menstruate at an early age
(before 12) or having a late menopause (after 55). The risk is also greater for women who
had their first child after the age of 30 and for those who never had children. Tall women
have a slightly higher risk for premenopausal breast cancer, and obese women have a higher
risk for breast cancer over age 50. These factors may all be related to a woman's natural
hormones.
Alcohol consumption and use of hormonal medications have been associated with increased
risk. Scientists are also studying whether diet, exercise, pesticides, electromagnetic
fields, engine exhausts, contaminants in food and water, and abortion and miscarriage may
be related to breast cancer risk. Some studies suggest that eating plenty of vegetables,
fruits, and whole grains or other lifestyle modifications may reduce risk.
4. What is BRCA1?
BRCA1 is the name of a gene located on chromosome 17 that is altered in certain
families with an inherited susceptibility to breast cancer. In these
families, women who inherit the altered gene have up to a 90 percent lifetime risk of
developing breast cancer. Researchers estimate that more than half of these women will be
diagnosed with breast cancer by age 50, and more than 85 percent will have a diagnosis of
breast cancer by age 70. Cancer risk may depend in part on the specific type and location
of the alteration within the gene.
Some families with BRCA1 alterations have a tendency to develop both breast and ovarian
cancers.
Women who inherit BRCA1 alterations tend to develop breast cancer at younger ages than
women in the general population. However, the disease may also occur at older ages in
women with BRCA1 alterations, and some may never get the disease. Men who inherit the
altered gene do not appear to have an increased risk of breast cancer, but can pass the
altered gene to their children. There is also some evidence for a slight increase in risk
of prostate cancer among carriers of a BRCA1 alteration.
5. How many women have an altered BRCA1 gene?
It is estimated that from one in 300, to one in 800, women in the United States have an
alteration in BRCA1.
6. Is there a pattern of inheritance for specific alterations in the BRCA1 gene?
A large number of different alterations has been identified in the BRCA1 gene. For the
most part, each BRCA1 family carries a particular, characteristic alteration.
Recently, Canadian and U.S. scientists identified one particular alteration in several
families with multiple cases of breast, or breast and ovarian cancers. These high-risk
families were all from an Ashkenazi Jewish background, with roots in Eastern Europe. So
far, information from 10 such families is published in the scientific literature.
This particular alteration is named 185delAG. Two adjacent pairs of DNA subunits
(nucleotides) are missing in the altered gene. This alteration, which is like taking two
letters out of one word in a long book chapter, causes the cell to shorten its translation
of the gene's usual instructions for making a protein. At the present time, scientists do
not know the function of the protein encoded by the normal gene.
7. What is the finding of the National Institutes of Health study which appears in
the Oct. 1, 1995 Nature Genetics?
NIH scientists found the 185delAG alteration in blood samples from 1 percent (8 of 858)
Ashkenazi Jews whose family or personal cancer histories are not known. This rate of
alteration in the BRCA1 gene is at least three times higher than all BRCA1 alterations
combined in the general population. They did not find the alteration in 815 other blood
samples from individuals not selected for ethnic origin.
8. What are the implications of the study?
The findings suggest that the 185delAG alteration in BRCA1 may be more common in the
Ashkenazi Jewish population than in other groups. However, from these results, scientists
still do not know whether, and to what degree, having the altered gene increases a woman's
risk of developing breast or ovarian cancers. To answer that question, they must study in
detail the family history of cancer in Jewish women who carry the 185delAG alteration.
NIH scientists are working closely with Jewish community leaders to conduct a follow-up
study of a sample of 3,000 to 5,000 people from the Ashkenazi Jewish population in the
Washington, D.C. area. Jewish community leaders have offered to help develop educational
materials, contact members of the Jewish community, field the study, and inform
participants and the Jewish community about the findings. Individual results will not be
revealed to participants in this phase of the study, but genetic testing and counseling
may be available once more is known about the effects of this particular alteration in the
BRCA1 gene.
The National Cancer Institute (NCI) also is planning a study on Long Island, New York,
where there is a sizeable Ashkenazi population, and other scientists in the United States
have also expressed interest in conducting studies of the 185delAG alteration.
The results of these new surveys may have implications for physician monitoring of
certain women for breast cancer occurrence, as well as for other research on breast and
ovarian cancers.
9. Do Ashkenazi Jews have a higher incidence of breast cancer than the general
population?
At this time, scientists cannot answer this question definitively. More than 90 percent
of the estimated six million U.S. Jews are Ashkenazi, according to Jewish sources.
Although some epidemiologists have suggested that Jewish women in the United States have
higher breast cancer rates, most studies have not looked at how much of the breast cancer
risk can be explained by known risk factors, and most breast cancer studies have not
recorded the religion of participants. In addition, the U.S. Census Bureau does not record
the religious background of individuals in the U.S. population.
10. Is it possible to test a person's DNA for the alterations in the BRCA1 gene
associated with breast cancer susceptibility?
Checking for possible alterations requires a thorough and complex examination of the
entire gene. Experts on BRCA1 examine blood samples from patients and family members. Such
tests at present should be done only in research laboratories because the tests are
labor-intensive and expensive. Interpretation of the results is technically difficult,
resulting in an unknown rate of false-negative findings (that is, the test does not show
an alteration, when one may be present).
Only a relatively few laboratories are able to perform the test reliably, and resources
for such testing are extremely limited. Because of the uncertainties surrounding
interpretation of the test results, a woman should accept testing only in a research
setting.
Before testing, participants in NIH-funded research studies receive counseling to help
them decide whether to go ahead with the process. Having the results before scientists
themselves fully understand the role of the gene in breast cancer development can have a
potentially adverse impact on individuals and their family members.
11. How will scientists test for the 185delAG alteration?
A blood test will tell scientists whether an individual's DNA has the 185delAG
alteration. At present, testing being done for research purposes offers individuals
education and counseling in addition to the blood test. Testing for this specific
alteration means that scientists will not have to sift through the entire gene for
alterations.
12. Why is counseling necessary?
Genetic testing for BRCA1 alterations is different from traditional medical tests.
Scientists may need blood samples from not just one, but several family members. Because
the issues surrounding gene testing for cancer predisposition are complex and
far-reaching, not just for the individual but for the entire family, participants who
would like to know their test results should consider discussing BRCA1 testing with a
genetics counselor and/or other health professional who is experienced in counseling on
genetics issues. One issue is genetic discrimination, an important consideration for
health and life insurance, employment, and child adoption. Another issue is personal well
being. While knowledge can be empowering, it also can be overwhelming and
anxiety-provoking.
Although research is underway to evaluate the possible social and psychological
implications of genetic testing, at the present time researchers do not know what
monitoring or medical followup to recommend to individuals who have an alteration in the
BRCA1 gene, and individuals are advised to seek help in understanding the personal and
social ramifications of BRCA1 testing. The NIH will be sponsoring studies to examine
various counseling and medical surveillance options for carriers of an altered BRCA1 gene.
13. Have other genes besides BRCA1 been implicated in breast cancer?
Yes, there are several, and diet and other environmental exposures also may be
important. About one-half of inherited breast cancers are associated with alterations in
the BRCA1 gene. Another gene, BRCA2, recently was mapped to chromosome 13, but has not yet
been isolated. An increased risk of breast cancer has also been observed in families with
other inherited diseases, such as ataxia telangiectasia; and the Li-Fraumeni syndrome,
characterized by multiple family members with soft tissue sarcoma, breast cancer, and
leukemia.
A number of other genes are associated with breast cancer. The changes in these genes
probably occurred during a person's lifetime, and are not inherited like the alterations
associated with hereditary breast cancer. Some of these genes have been implicated in
causing breast cancer, while others are believed to be involved in disease invasion and
metastasis. These include the genes named p53, AT, and a group known as GADD repair genes.
Others being studied include the RB suppressor gene, the HER-2/neu oncogene, and genes
that help regulate the cell cycle.
14. Are tests for alterations in these genes available to the public?
Generally, no. At the present time, several gene tests are being offered in research
studies as a way to help track patients' progress during cancer treatment. No gene tests
are currently available for determining risk of breast cancer in the general population.
15. What about other groups, such as African Americans, who also may have higher
breast cancer incidence at younger ages than other American women?
Both NCI and the National Human Genome Research Institute (NHGRI) are conducting
research to examine whether alterations in BRCA1 are associated with breast cancer risk in
African American families having multiple individuals with breast cancer.
16. Where can a woman go to be counseled and/or tested if she is concerned about a
possible inherited risk for breast cancer?
At the present time, only a limited number of centers are able to offer counseling and
testing. Most family physicians will not be able to offer testing at present. A
woman with a mother or sister with breast cancer who is interested in being tested will
need to ask her physician to contact a testing center for more information. Contact the
National Cancer Institute's Cancer Information Service at 1-800-4-CANCER for information
about breast cancer and for sources of information about counseling and testing options.
The Cancer Information Service (CIS), a program of the National Cancer Institute,
provides a nationwide telephone service for cancer patients and their families, the
public, and health care professionals. CIS information specialists have extensive training
in providing up-to-date and understandable information about cancer and cancer research.
They can answer questions in English and Spanish and can send free printed material. In
addition, CIS offices serve specific geographic areas and have information about
cancer-related services and resources in their region. The toll-free number of the CIS is
1-800-4-CANCER (1-800-422-6237).
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