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CANSER, in medicine, common
term for neoplasms, or tumors, that are
malignant. Like benign tumors, malignant tumors do
not respond to body mechanisms that limit
cell growth. Unlike benign tumors, malignant
tumors consist of undifferentiated, or
unspecialized, cells that show an atypical cell structure
and do not function like the normal cells
from the organ from which they derive.
Cancer cells, unlike normal cells, lack
contact inhibition; cancer cells growing
in laboratory tissue culture do not stop
growing when they touch each other on
a glass or other solid surface but grow
in masses several layers deep.
Loss of contact inhibition accounts for
two other characteristics of cancer cells:
invasiveness of surrounding tissues, and
metastasis, or spreading via the lymph
system or blood to other tissues and organs.
Whereas normal cells have a limited lifespan
controlled by the telomere gene, which
signals the end of the cell line, cancer
cells contain telomerase, an enzyme that
alters the telomere gene and allows the
cell to continue to divide. Cancer tissue,
growing without limits, competes with normal
tissue for nutrients, eventually killing
normal cells by nutritional deprivation.
Cancerous tissue can also cause secondary
effects, in which the expanding malignant
growth puts pressure on surrounding tissue
or organs or the cancer cells metastasize
and invade other organs.
Virtually all organs and tissues are susceptible
to cancer. Cancers are usually named for
their site of origin. Cancer cells that
spread to other organs are similar to those
of the original tumor, therefore these
secondary (metastatic) cancers are still
named for their primary site even though
they may have invaded a different organ.
For example, lung cancer that has spread
to the brain is called metastatic lung
cancer, rather than brain cancer. Carcinoma
in situ refers to a cancer that has not
spread. (See neoplasm for more on cancer
nomenclature.)
Cancer is the second leading cause of
death in the United States. Lung cancer
is the leading cause of cancer death in
adults; leukemia is the most common cancer
in children. Other common types of cancer
include breast cancer (in women), prostate
cancer (in men), and colon cancer (see
also Hodgkin's disease). The incidence
of particular cancers varies around the
world and sometimes according to ethnic
group. For instance, African Americans
have comparatively higher cancer rates
and cancer mortality rates. It is unclear
whether this is due to differences in exposure
or to biological susceptibility. The number
of diagnosed cases of cancer rose steadily
in the United States for decades, but in
1998 it was announced that the number of
new cases had begun to decline.
Causes of Cancer
Cancer results from mutations of certain
genes that allow the cells to begin their
uncontrolled growth. These mutations are
either inherited or acquired. Acquired
mutations are caused by repeated insults
from triggers (e.g., cigarette smoke or
ultraviolet rays) referred to as carcinogens.
There is usually a latency period of years
or decades between exposure to a carcinogen
and the appearance of cancer. This, combined
with the individual nature of susceptibility
to cancer, makes it very difficult to establish
a cause for many cancers.
The most significant avoidable carcinogens
are the chemical components of tobacco
smoke (see smoking). Dietary components,
like excessive consumption of alcohol or
of foods high in fat and low in fiber rather
than fruits and vegetables that contain
antioxidants and necessary micronutrients,
have also been linked with various cancers.
Some cancers may be triggered by hormone
imbalances. For example, some daughters
of mothers who had been given DES (diethylstilbestrol)
during pregnancy to prevent miscarriage
developed vaginal adenocarcinomas as young
women. Aflatoxins are natural mold byproducts
that can cause cancer of the liver.
Certain carcinogens present occupational
hazards. For example, in the asbestos industry,
workers have a high probability of developing
lung and colon cancer or a particularly
virulent cancer of the mesothelium (the
lining of the chest and abdomen). Benzene
and vinyl chloride are other known industrial
carcinogens.
X rays and radioactive elements are also
carcinogenic; the high incidence of leukemia
and other cancers in Japanese survivors
of the atomic bombing of Hiroshima and
Nagasaki and the increased incidence of
thyroid cancer after the Chernobyl nuclear
disaster give evidence of this. Exposure
to the ultraviolet radiation of sunlight
is the leading cause of skin cancer.
Many other substances have been identified
as carcinogenic to a greater or lesser
extent, including chemicals in pesticides
that leave residues on foods. The Delaney
clause, an amendment (1958) to the U.S.
Food, Drug, and Cosmetic Act that prohibits
even minuscule amounts of carcinogens in
the food supply, has provided the impetus
for the investigation of many such chemicals
but has also been a source of controversy
between industry and environmentalists.
In the early 20th cent., the American
virologist Peyton Rous showed that certain
sarcomas affecting fowl could be transmitted
by injection of an agent invisible under
the microscope and later indentified as
an RNA-containing virus. Other research
uncovered oncogenic, or tumor-causing,
viruses, first in experimental animals
and then in humans. The Epstein-Barr virus,
a member of the herpesvirus group, has
been linked with a number of human cancers,
including the lymphomas that often occur
in immunosuppressed people, such as people
with AIDS. Several human papillomaviruses
(HPV) have also been shown to initiate
cancers. For example, some types of HPV
cause genital warts known as condylomata
acuminata, which can lead to invasive cancer
of the cervix, vulva, vagina, or penis,
and another human papillomavirus has been
associated with some forms of Kaposi's
sarcoma. In addition, hepatitis B has been
shown to increase the risk of liver cancer.
Bacteria have also been associated with
cancer. For example, the Helicobacter pylori
bacterium that causes many ulcers is also
associated with an increased risk of stomach
cancer.
Cancer Susceptibility
Risk to humans from carcinogens depends
upon the dose and a person's biologic susceptibility.
Factors influencing a person's biological
susceptibility to cancer include age, sex,
immune status, nutritional status, genetics,
and ethnicity. Only 5% of all cancers in
the United States are thought to be explained
by inherited genetic mutations. Known genes
associated with hereditary cancer include
the aberrant BRCA1 and BRCA2 genes that
increase breast cancer risk and the HNPCC
gene that is linked with colon cancer.
In hereditary forms, it is often the normal
gene of the allele that is injured or destroyed,
leaving the abnormal inherited gene in
control. Nonhereditary cancers sometimes
involve the same gene mutations that hereditary
forms have.
Tumor Development
Most bodily insults by carcinogens come
to nothing because DNA has built-in repair
mechanisms, but repeated insults can eventually
result in mutations or altered gene expression
in key genes called oncogenes and tumor-suppressor
genes. Oncogenes produce growth factors,
substances that signal a cell to grow and
divide into daughter cells; tumor-suppressor
genes (such as the p16, p53, and BRCA1
genes) normally produce a negative growth
factor that tells a cell when to stop dividing.
The abnormally inactivated tumor-suppressor
gene or the abnormally activated oncogene
is inherited by each of the cell's daughter
cells, and a tumor develops. In many cases
tumors remain small and in one place (in
situ) for years, but some develop their
own blood vessels (a process known as angiogenesis)
and begin to grow and spread.
Symptoms
The classic symptoms of cancer are rapid
weight loss; a change in a wart or mole;
a sore that does not heal; difficulty swallowing;
chronic hoarseness, blood in phlegm, urine,
or stool (a consequence of angiogenesis);
chronic abdominal pain; a change in size
or shape of the testes; a change in bowel
habits; a lump in the breast; and unusual
vaginal bleeding. Many of these and other
symptoms are often nonspecific, e.g., weakness,
loss of appetite, and weight loss, and
thus are not obvious in the early stages.
Sometimes the side effects of tumor growth
are more severe than the actual effects
of the malignancy; for example, some tumors
secrete materials such as serotonin and
histamine that can cause drastic vascular
changes. Conversely, cancers that destroy
tissue may also have serious effects, e.g.,
malignant destruction of bone tissue may
raise the blood level of calcium.
Prevention and Detection
As more has been learned about cancer,
emphasis on prevention and early detection
has increased. Cessation of smoking and
other tobacco use is the most important
controllable means of prevention; smoking
causes about 30% of the cancer deaths in
the United States. A diet low in fat and
high in fiber, including a variety of fruits
and vegetables (especially those high in
antioxidants), is also recommended. Effective
protection against the rays of the sun
is recommended to avoid skin cancer. Another
preventive approach is vaccination against
cancer-causing viruses, such as the hepatitis
B virus.
Cancers caught early, before metastasis,
have the best cure rates. A number of screening
tools are now available to allow early
detection and treatment. Among these are
monthly breast self-examinations and regular
mammography and Pap tests for women, regular
self-examination of the testes for young
men, and, for older men, regular examination
of the prostate gland with blood tests
for prostate-specific antigen (PSA) tumor
marker (a substance in the body that heralds
an increased cancer risk). Sigmoidoscopy
plus physical examination and laboratory
tests for carcinoembryonic antigen (CEA)
are recommended for detection of colon
cancer. Self-examination of the skin is
important for the early detection of skin
cancers. Suspicion of a tumor may be confirmed
by X-ray study, endoscopy (see endoscope),
blood tests for various tumor markers,
and biopsy from which the cells are examined
by a pathologist for malignancy.
Treatment
Developments in the treatment of cancer
have led to greatly improved survival and
quality of life for cancer patients in
the past three decades. Traditionally,
cancer has been treated by surgery, chemotherapy,
and radiation therapy. In recent years
immunotherapy has been added to that list.
New drugs and techniques are constantly
being researched and developed, such as
antiangiogenic agents (e.g., angiostatin
and endostatin), genetically engineered
monoclonal antibodies, retinoid agents,
and vaccine agents (stimulating the immune
system).
For most kinds of cancer, surgery remains
the primary treatment. It is most effective
if the cancer is caught while still localized.
Some cancers that spread to the lymph system
are sometimes treated by extensive surgical
removal of tissue, but the trend is toward
more conservative procedures (see mastectomy).
Cryosurgery, the use of extreme cold, and
electrodessication, the use of extreme
heat, are also being used to kill cancerous
tissue and the surrounding blood supply.
If the cancer has metastasized, surgery
is often replaced by or followed by radiation
therapy (which is a localized therapy)
and chemotherapy (which is a system-wide
therapy).
For some cancers, radiation therapy—either
from an external beam or from implanted
radioactive pellets—is the primary
treatment. The usual forms are X rays and
gamma rays. Use of radioactive elements
specific for particular target organs,
such as radioactive iodine specific for
the thyroid gland, is effective in treating
malignancies of those organs.
Cytotoxic chemotherapy is used as a primary
treatment for some cancers, such as lymphomas
and leukemias or as an addition to surgery
or radiation therapy. Cytotoxic drugs (drugs
that are toxic to cells) are aimed at rapidly
proliferating cells and interfere with
nucleic acid and protein synthesis in the
cancer cell, but they are often toxic to
normal rapidly proliferating cells, such
as bone marrow and hair cells. Often a
combination of cytotoxic drugs is used.
Drugs that reduce side effects may be added
to the treatment, such as antinausea agents.
Hormonal chemotherapy is based upon the
fact that the growth of some malignant
tumors (specifically those of the reproductive
organs) is influenced by reproductive hormones.
Tamoxifen is a naturally occurring estrogen
inhibitor used to prevent breast cancer
recurrences. Flutamide is sometimes used
in prostate cancer to inhibit androgen
uptake. Sex-hormone related drugs such
as DES and tamoxifen, which may be carcinogenic
under some conditions, have proven to be
protective under others.
More specifically targeted drug therapies
have begun to be explored as a better understanding
of the molecular biology of individual
cancers has been developed. Such drugs
are designed to kill only cancer cells
while having fewer side effects. Gleevec
(STI-571), which is used to treat chronic
myelogenous leukemia and some other cancers,
inhibits certain kinase receptors that
become hyperactive in cancer cells, resulting
in the cells' rapid reproduction.
Immunotherapy (sometimes called biological
therapy) uses substances that help the
body mobilize its immune defenses. Some
attack the tumor itself, while others bolster
the body's ability to withstand conventional
chemotherapy treatment. Other new or experimental
therapies include drugs that inhibit angiogenesis
and photodynamic therapy, in which a patient
is given a drug to make the tumor light-sensitive,
after which the tumor is exposed to bright
laser light. The best choice of treatment
will increasingly be influenced by the
growing field of molecular pathology, in
which characteristics of individual cancers
(e.g., virulence or resistance to a particular
treatment) can be revealed by analysis
of their genetic characteristics rather
than by the microscope.
Besides treatment of the cancer itself,
progress has been made in the management
of the chronic pain that often accompanies
cancer and in the education of patients
and physicians in such techniques as biofeedback,
acupuncture, and meditation and the appropriate
use of narcotics and other medications.
Because of improvements in early detection
and treatment, many more people are now
living with cancer. Over half of all people
with cancer now survive for five or more
years.
Bibliography
See S. S. Lang and R. B. Patt, You Don't
Have to Suffer (1994); P. Greenwald et
al., Cancer Prevention and Control (1995);
M. Dollinger et al., Everyone's Guide to
Cancer Therapy (3d ed. 1997); C. N. Coleman,
Understanding Cancer (1998). See also publications
of the National Cancer Institute and the
American Cancer Society. |
