EMBARGOED FOR RELEASE
6:00 p.m. EDT
Thursday, June 22, 1995
Patricia Newman
NCI Press Office
(301) 496-6641
Questions and Answers: Ataxia Telangiectasia
- What is ataxia telangiectasia?
Ataxia telangiectasia (A-T) is a rare, recessive genetic disorder of
childhood that occurs in about 1/40,000 and 1/100,000 persons worldwide.
The ailment is progressive. By their teens, patients with A-T are
frequently wheelchair-bound.
The disease is characterized by neurologic problems, particularly
abnormalities of balance, recurrent serious sinus and respiratory
infections, and dilated blood vessels in the eyes and on the surface of
the skin. Patients usually have immune system abnormalities and are
very sensitive to the effects of radiation treatments.
In the United States, where recurrent infections typical of the disorder
are usually controlled by antibiotics, patients are at high risk of
developing and dying of cancer, particularly leukemias and lymphomas.
2. Is the disorder curable?
There is no cure for A-T at the present time. With the cloning and
eventual sequencing of the gene (named ATM), several avenues of research
to develop better treatment become possible, including: (1) gene
therapy; (2) rational drug design; and (3) direct replacement of the
functional protein.
3. What does it mean that the disorder is recessive?
A disease is recessive when a person inherits the predisposing gene from
both parents, each of whom transmits one copy of the abnormal gene to
their child.
4. What is a carrier?
A carrier is a person with one normal and one altered copy of a gene
that is linked to a particular disease. These individuals usually do
not realize they are carriers, because the disease is not present, or
its signs and symptoms are very mild.
5. How many A-T carriers are there in the United States?
An estimated one percent, or 2 1/2 million, of the U.S. population may
be carriers for A-T.
6. How do I know if I am a carrier?
In the past, carriers have been identified chiefly because they are
parents of a child with A-T. In a small number of cases, carriers have
been identified through extensive laboratory and clinical studies of
families where A-T has occurred. With the cloning of the ATM gene,
however, scientists will be able to devise a test to detect A-T carri-
ers. To do this, they take advantage of what they know about alter-
ations to the gene in a particular family. Because different carriers
will have different mutations in the gene, devising a diagnostic gene
test may be difficult.
7. What cancers are increased in A-T patients?
At least 10 percent of A-T patients develop cancer. Most of these are
cancers of the lymphoid tissues (leukemias and lymphomas), but one-fifth
of the cancers occur in the stomach, brain, ovary, skin, liver, larynx,
parotid gland, and breast.
8. What cancers are increased in A-T carriers?
Definitive information does not yet exist to answer this question, and
must await the development of a test to identify ATM gene carriers.
Some studies of the families of A-T patients have reported a 3-4 fold
increased risk of cancer, including breast cancer; this finding is
controversial. Current estimates of risk are based on studies of
selected families of A-T patients. The cloning of the ATM gene now
allows scientists worldwide to evaluate suggestions of increased risk
for cancer, and NCI is
collaborating on several studies that combine epidemiology with molecu-
lar analysis to address this question.
9. Are A-T patients sensitive to radiation?
A-T patients have an increased sensitivity to ionizing radiation, the
type found in
X-rays. When cultured in the laboratory, the blood and skin cells of
these patients have markedly reduced ability to replicate and form cell
colonies after X-ray
exposure. Scientists believe that the ATM gene is one of at least three
genes,
(ATM, p53 and GADD45) involved in this cell cycle arrest.
10. Are ATM gene carriers also sensitive to the effects of radiation?
This is a question needing further study, and the cloning of the ATM
gene will make new studies of carriers possible. When cultured in the
laboratory, the blood and skin cells of known ATM gene carriers are
intermediate in their sensitivity to X-rays, compared to A-T patients
and the general public.
11. Does their increased sensitivity to radiation, compared to the general
public, make it dangerous for carriers to have diagnostic X-rays?
There is no evidence to support this. At the dosages of radiation
delivered by today's technology, diagnostic tests are not considered
harmful to carriers.
12. Are X-rays harmful to A-T patients?
A-T patients are sensitive to the effects of radiation and should be
monitored for adverse effects. However, they do receive diagnostic X-
rays when necessary.
The information about radiation sensitivity in A-T comes largely from
observations of A-T patients who undergo radiation treatments, especial-
ly for cancer, and also from laboratory studies on skin and blood cells.
Physicians who treat A-T patients limit
X-ray exposures by using the most modern equipment and techniques
available, but they do recommend these diagnostic tests when they are
needed.
Now that the ATM gene has been isolated, scientists will be able to
study the nature of the radiation sensitivity observed in cells from A-T
patients, as well as any
intermediate level of radiation sensitivity observed in cells from known
carriers.
13. Suppose I learn I am an A-T carrier. Will mammography increase my
chances of getting breast cancer?
There is no definitive evidence that A-T carriers of any age have
increased sensitivity to X-rays from mammograms or other diagnostic
tests. For women 50 and older, th benefits of mammography have been
demonstrated clearly.
For younger women, those 40-49, NCI continues to recommend discussing
individual risk issues with your physician. The influence, if any, of
X-rays on the breast cells of premenopausal women is theoretical and
will be studied further, now that the ATM gene is cloned.
14. Are there any alternatives to mammography on the horizon?
Recent technological modifications to mammography result in delivery of
lower radiation doses than 20 years ago. In addition, NCI is sponsoring
the development and clinical testing of non-ionizing breast imaging
technologies, such as magnetic resonance imaging, ultrasound and PET.
15. What about environmental sources of radiation, such as cellular phones.
Should A-T carriers avoid these exposures?
To date, there have been no definitive studies linking non-ionizing
radiation, such as that from cellular phones, to cancer. NCI currently
is evaluating non-ionizing radiation from a variety of sources to assess
thoroughly any potential cancer risks.
16. What studies does NCI have under way or planned to answer these questions
more definitively?
NCI is sponsoring a wide variety of research on DNA repair, radiation
sensitivity and resistance, and A-T. Clinical scientists at the NCI
have over 30 years of experience with A-T, and are continuing research
to develop better diagnostic tests, immune dysfunction analyses, and
treatments.
In addition, NCI epidemiologists are collaborating in several studies of
A-T, including population-based studies of the risk of cancer in A-T
patients and their relatives in Denmark that are being expanded to other
Scandinavian countries; a study of
early-onset breast cancer among X-ray technologists, whose blood samples
are being examined for mutations in the BRCA1 and ATM genes; and ongoing
studies for over 20 years of radiation-induced breast cancer. These
latter studies include analysis of scoliosis patients who as young girls
received intense spinal X-rays to monitor the growth spurt; women with
tuberculosis who received hundreds of chest fluoroscopic X-rays to
monitor lung collapse; survivors of the atomic bombings in Hiroshima and
Nagasaki; women with breast cancer who developed secondary breast cancer
in the contralateral breast; women with Hodgkin's disease treated with
radiotherapy, and others. In a number of these studies, blood and tumor
samples are being evaluated for the influence of genes such as p53 and
BRCA1 on radiation-induced breast cancer risk, and ATM gene studies will
be possible in the near future.
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