Cancer
Cancer is a class of diseases characterized by
uncontrolled cell division and the ability of
these cells to invade other tissues, either by
direct growth into adjacent tissue (invasion)
or by migration of cells to distant sites
(metastasis).
This unregulated growth is caused by damage to
DNA, resulting in mutations to vital genes that
control cell division, among other functions.
One or more of these mutations, which can be
inherited or acquired, can lead to uncontrolled
cell division and tumor formation.
Tumor
("swelling" in Latin) refers to any abnormal
mass of tissue, but may be either malignant
(cancerous) or benign (non cancerous). Only
malignant tumors are capable of invading other
tissues or metastasizing.
Cancer can cause many different symptoms,
depending on the site and character of the
malignancy and whether there is metastasis. A
definitive diagnosis usually requires the
microscopic examination of tissue obtained by
biopsy. Once diagnosed, cancer is usually
treated with surgery, chemotherapy and/or
radiation.
If untreated, most cancers eventually cause
death; cancer is one of the leading causes of
death in developed countries. Most cancers can
be treated and many cured, especially if
treatment begins early. Many forms of cancer are
associated with environmental factors, which may
be avoidable. Smoking tobacco leads to more
cancers than any other environmental factor.
Diagnosing cancer
Most cancers are initially recognized either
because signs or symptoms appear or through
screening. Neither of these lead to a definitive
diagnosis, which usually requires a biopsy. Some
cancers are discovered accidentally during
medical evaluation of an unrelated problem.
Signs and symptoms
Roughly, cancer symptoms can be divided into
three groups:
-Local
symptoms:
unusual lumps or swelling (tumor),
hemorrhage (bleeding), pain and/or ulceration.
Compression of surrounding tissues may cause
symptoms such as jaundice.
-Symptoms of
metastasis spreading:
enlarged lymph
nodes, cough and hemoptysis, hepatomegaly
(enlarged liver), bone pain, fracture of
affected bones and neurological symptoms.
Although advanced cancer may cause pain, it is
usually not the first symptom.
-Systemic symptoms:
weight loss, poor appetite and cachexia
(wasting), excessive sweating (night sweats),
anemia and specific paraneoplastic phenomena,
i.e. specific conditions that are due to an
active cancer, such as thrombosis or hormonal
changes.
Every single item in the above list can be
caused by a variety of conditions (a list of
which is referred to as the differential
diagnosis). Cancer may be a common or uncommon
cause of each item.
Biopsy
A cancer may be suspected for a variety of
reasons, but the definitive diagnosis of most
malignancies must be confirmed by microscopic
examination of the cancerous cells by a
pathologist. The procedure of obtaining cells
and/or pieces of tissue, and their examination,
is referred to as a biopsy. The tissue diagnosis
indicates the type of cell that is
proliferating, its severity (degree of
dysplasia), and its extent and size. Cytogenetic
and immunohistochemistry tests may provide
information about future behavior of the cancer
(prognosis) and best treatment.
All cancers can be cured if entirely removed,
and sometimes this can be accomplished by the
biopsy procedure. When the whole mass of
abnormal tissue (the "lesion") is removed, the
borders of the sample are examined closely to
see if all malignant tissue has truly been
excised. If the cancer has spread to other sites
in the body (metastasis), complete surgical
excision is impossible.
The nature of the biopsy depends on the organ
that is sampled. Many biopsies (such as those of
the skin, breast or liver) can happen on an
outpatient basis. Biopsies of other organs are
performed under anesthesia and require surgery.
Screening
Cancer screening is a test to detect unsuspected
cancers in the population. Screening tests
suitable for large numbers of healthy people
must be relatively affordable, safe,
non-invasive procedures with acceptably low
rates of false positive results. If signs of
cancer are detected, more definitive and
invasive follow up tests are performed to
confirm the diagnosis.
Screening for cancer can lead to earlier
diagnosis. Early diagnosis may lead to extended
life. A number of different screening tests have
been developed. Breast cancer screening can be
done by breast self-examination. Screening by
regular mammograms detects tumors even earlier
than self-examination, and many countries use it
to systematically screen all middle-aged women.
Colorectal cancer can be detected through fecal
occult blood testing and colonoscopy, which
reduces both colon cancer incidence and
mortality, presumably through the detection and
removal of premalignant polyps. Similarly,
cervical cytology testing (using the Pap smear)
leads to the identification and excision of
precancerous lesions. Over time, such testing
has been followed by a dramatic reduction of
cervical cancer incidence and mortality.
Testicular self-examination is recommended for
men beginning at the age of 15 years to detect
testicular cancer. Prostate cancer can be
screened for by a digital rectal exam along with
prostate specific antigen (PSA) blood testing.
Screening for cancer is controversial in cases
when it is not yet known if the test actually
saves lives. The controversy arises when it is
not clear if the benefits of screening outweigh
the risks of follow-up diagnostic tests and
cancer treatments. For example: when screening
for prostate cancer, the PSA test may detect
small cancers that would never become life
threatening, but once detected will lead to
treatment. This situation, called over
diagnosis, puts men at risk for complications
from unnecessary treatment such as surgery or
radiation. Follow-up procedures used to diagnose
prostate cancer (prostate biopsy) may cause side
effects, including bleeding and infection.
Prostate cancer treatment may cause incontinence
(inability to control urine flow) and erectile
dysfunction (erections inadequate for
intercourse). Similarly, for breast cancer,
there have recently been criticisms that breast
screening programs in some countries cause more
problems than they solve. This is because
screening of women in the general population
will result in a large number of women with
false positive results which require extensive
follow-up investigations to exclude cancer,
leading to having a high number-to-treat (or
number-to-screen) to prevent or catch a single
case of breast cancer early.
Cervical cancer screening via the Pap smear has
the best cost-benefit profile of all the forms
of cancer screening from a public health
perspective as, as a cancer, it has clear risk
factors (sexual contact), the natural
progression of cervical cancer is that it
normally spreads slowly over a number of years
therefore giving more time for the screening
program to catch it early and the test itself is
easy to perform and relatively cheap.
For these reasons, it is important that the
benefits and risks of diagnostic procedures and
treatment be taken into account when considering
whether to undertake cancer screening.
Use of medical imaging to search for cancer in
people without clear symptoms is similarly
marred with problems. There is a significant
risk of detection of what has been recently
called an (incidentaloma)
- a benign lesion that may be interpreted as a
malignancy and be subjected to potentially
dangerous investigations.
Types of cancer
Cancer cells within a tumor are the descendants
of a single cell, even after it has
metastasized. Hence, a cancer can be classified
by the type of cell in which it originates and
by the location of the cell.
Carcinomas originate in epithelial cells (e.g.
the digestive tract or glands). Hematological
malignancies, such as leukaemia and lymphoma,
arise from blood and bone marrow. Sarcoma arises
from connective tissue, bone or muscle. Melanoma
arises in melanocytes. Teratoma begins within
germ cells.
Adult
cancers
In the USA and other developed countries, cancer
is presently responsible for about 25% of all
deaths. On a yearly basis, 0.5% of the
population is diagnosed with cancer.
For adult males in
the United States, the most common cancers are
prostate cancer (33% of all cancer cases), lung
cancer (13%), colorectal cancer (10%), bladder
cancer (7%) and cutaneous melanoma (5%). As a
cause of death lung cancer is the most common
(31%) cause, followed by prostate cancer (10%),
colorectal cancer (10%), pancreatic cancer (5%)
and leukaemia (4%).
For adult females in the United States, breast
cancer is the most common cancer (32% of all
cancer cases) followed by lung cancer (12%),
colorectal cancer (11%), endometrial cancer (6%,
uterus) and non-Hodgkin's lymphoma (4%). By
cause of death, lung cancer is again the most
common (27% of all cancer deaths), followed by
breast cancer (15%), colorectal cancer (10%),
ovarian cancer (6%) and pancreatic cancer (6%).
These statistics vary substantially in other
countries.
Other cancers not mentioned:
*
Epithelial
tumors:
skin cancer (this is in fact the most common
cancer but often not classified as such in
health statistics), cervical cancer, anal
carcinoma, esophageal cancer, hepatocellular
carcinoma (in the liver), laryngeal cancer,
renal cell carcinoma (in the kidneys), stomach
cancer, many testicular cancers, and thyroid
cancer.
*
Hematological
malignancies (blood and bone marrow):
leukaemia,
lymphoma, multiple myeloma.
*
Sarcomas:
osteosarcoma (in bone), chondrosarcoma (arising
from cartilage), rhabdomyosarcoma (in muscle).
*Miscellaneous
origin:
brain tumors, gastrointestinal stromal tumors
(GIST), mesothelioma (in the pleura or
pericardium), thymoma and teratomas, melanoma
Childhood
cancers
Cancer can also occur in young children and
adolescents. Here, the aberrant genetic
processes that fail to safeguard against the
clonal proliferation of cells with unregulated
growth potential occur early in life and can
progress quickly.
The age of peak incidence of cancer in children
occurs during the first year of life. Leukaemia
(usually ALL) is the most common infant
malignancy (30%), followed by the central
nervous system cancers and neuroblastoma. The
remainder consists of Wilms' tumor, lymphomas,
rhabdomyosarcoma (arising from muscle),
retinoblastoma, osteosarcoma and Ewing's
sarcoma.
Female infants and male infants have essentially
the same overall cancer incidence rates, but
white infants have substantially higher cancer
rates than black infants for most cancer types.
Relative survival for infants is very good for
neuroblastoma, Wilms' tumor and retinoblastoma,
and fairly good (80%) for leukemia, but not for
most other types of cancer
Causes
and pathophysiology:
Origins
of cancer:
Cell division (proliferation) is a physiological
process that occurs in almost all tissues and
under many circumstances. Normally the balance
between proliferation and cell death is tightly
regulated to ensure the integrity of organs and
tissues. Mutations in DNA that lead to cancer
disrupt these orderly processes.
The uncontrolled and often rapid proliferation
of cells can lead to either a benign tumor or a
malignant tumor (cancer). Benign tumors do not
spread to other parts of the body or invade
other tissues, and they are rarely a threat to
life unless they extrinsically compress vital
structures. Malignant tumors can invade other
organs, spread to distant locations
(metastasize) and become life-threatening.
Molecular
biology:
Cancers are caused by a series of mutations.
Each mutation alters the behavior of the cell
somewhat.
Carcinogenesis (meaning literally, the creation
of cancer) is the process of derangement of the
rate of cell division due to damage to DNA.
Cancer is, ultimately, a disease of genes.
Typically, a series of several mutations is
required before a normal cell transforms into a
cancer cell. The process involves both
proto-oncogenes and tumor suppressor genes.
Proto-oncogenes are involved in signal
transduction by coding for a chemical
"messenger", produced when a cell undergoes
protein synthesis. These messengers, send
signals based on the amount of them present to
the cell or other cells, telling them to undergo
mitosis, in order divide and reproduce. When
mutated, they become oncogenes and over express
the signals to divide, and thus cells have a
higher chance to divide excessively.
Frustratingly, the chance of cancer cannot be
reduced by removing proto-oncogenes from the
human genome as they are critical for growth,
repair and homeostasis of the body. It is only
when they become mutated, that the signals for
growth become excessive.
Tumor suppressor genes code for chemical
messengers that command cells to slow or stop
mitosis in order to allow DNA repair. This is
done by special enzymes which detect any
mutation or damage to DNA, such that the mistake
is not carried on to the next generation. Tumor
suppressor genes are usually triggered by
signals that DNA damage has occurred. In
addition to inhibiting mitosis, they can code
for such enzymes themselves, or sending signals
to activate such enzymes. However, a mutation
can damage the tumor suppressor gene itself, or
the signal pathway which activates it,
"switching it off". The invariable consequence
of this is that DNA repair is hindered or
inhibited: DNA damage accumulates without
repair, inevitably leading to cancer.
In general, mutations in both types of genes are
required for cancer to occur. For example, a
mutation limited to one oncogene would be
suppressed by normal mitosis control (the
Knudson or 1-2-hit hypothesis) and tumor
suppressor genes. A mutation to only one tumor
suppressor gene would not cause cancer either,
due to the presence of many "backup" genes that
duplicate its functions. It is only when enough
proto-oncogenes have mutated into oncogenes, and
enough tumor suppressor genes deactivated or
damaged, that the signals for cell growth
overwhelm the signals to regulate it, that cell
growth quickly spirals out of control.
Mutations can have various causes. Particular
causes have been linked to specific types of
cancer. Tobacco smoking is associated with lung
cancer. Prolonged exposure to radiation,
particularly ultraviolet radiation from the sun,
leads to melanoma and other skin malignancies.
Breathing asbestos fibers is associated with
mesothelioma. In more general terms, chemicals
called mutagens and free radicals are known to
cause mutations. Other types of mutations can be
caused by chronic inflammation, as neutrophil
granulocytes secrete free radicals that damage
DNA. Chromosomal translocations, such as the
Philadelphia chromosome, are a special type of
mutation that involve exchanges between
different chromosomes.
Many mutagens are also carcinogens, but some
carcinogens are not mutagens. Examples of
carcinogens that are not mutagens include
alcohol and oestrogen. These are thought to
promote cancers through their stimulating effect
on the rate of cell mitosis. Faster rates of
mitosis increasingly leave less window space for
repair enzymes to repair damaged DNA during DNA
replication, increasingly the likelihood of a
genetic mistake. A mistake made during mitosis
can lead to the daughter cells receiving the
wrong number of chromosomes, which leads to
aneuploidy and may lead to cancer.
Mutations can also be inherited. Inheriting
certain mutations in the BRCA1 gene, a tumor
suppressor gene, renders a woman much more
likely to develop breast cancer and ovarian
cancer. Mutations in the Rb1 gene predispose to
retinoblastoma, and those in the APC gene lead
to colon cancer.
Some types of viruses can cause mutations. They
play a role in about 15% of all cancers. Tumor
viruses, such as some retroviruses,
herpesviruses and papillomaviruses, usually
carry an oncogene or a gene inhibits normal
tumor suppression in their genome.
It is impossible to tell the initial cause for
any specific cancer. However, with the help of
molecular biological techniques, it is possible
to characterize the mutations or chromosomal
aberrations within a tumor, and rapid progress
is being made in the field of predicting
prognosis based on the spectrum of mutations in
some cases. For example, up to half of all
tumors have a defective p53 gene, a tumor
suppressor gene also known as "the guardian of
the genome". This mutation is associated with
poor prognosis, since those tumor cells are less
likely to go into apoptosis (programmed cell
death) when damaged by therapy. Telomerase
mutations remove additional barriers, extending
the number of times a cell can divide. Other
mutations enable the tumor to grow new blood
vessels to provide more nutrients, or to
metastasize, spreading to other parts of the
body.
Malignant tumors cells have distinct properties:
-
Evading apoptosis
-
Unlimited growth potential (immortalitization)
-
Self-sufficiency of growth factors
-
Insensitivity to anti-growth factors
-
Increased cell division rate
-
Altered ability to differentiate
-
No ability for contact inhibition
-
Ability to invade neighbouring tissues
-
Ability to build metastases at distant sites
-
Ability to promote blood vessel growth
(angiogenesis)
A cell that degenerates into a tumor cell does
not usually acquire all these properties at
once, but its descendant cells are selected to
build them. This process is called clonal
evolution. A first step in the development of a
tumor cell is usually a small change in the DNA,
often a point mutation, which leads to a genetic
instability of the cell. The instability can
increase to a point where the cell loses whole
chromosomes, or has multiple copies of several.
Also, the DNA methylation pattern of the cell
changes, activating and deactivating genes
without the usual control. Cells that divide at
a high rate, such as epithelial, show a higher
risk of becoming tumor cells than those which
divide less, for example neurons.
Morphology
Tissue can be organized in a continuous spectrum
from normal to cancer.
Cancer tissue has a distinctive appearance under
the microscope. Among the distinguishing traits
are a large number of dividing cells, variation
in nuclear size and shape, variation in cell
size and shape, loss of specialized cell
features, loss of normal tissue organization,
and a poorly defined tumor boundary.
Immunohistochemistry and other molecular methods
may characterise specific markers on tumor
cells, which may aid in diagnosis and prognosis.
Biopsy and microscopical examination can also
distinguish between malignancy and hyperplasia,
which refers to tissue growth based on an
excessive rate of cell division, leading to a
larger than usual number of cells but with a
normal orderly arrangement of cells within the
tissue. This process is considered reversible.
Hyperplasia can be a normal tissue response to
an irritating stimulus, for example callus.
Dysplasia is an abnormal type of excessive cell
proliferation characterized by loss of normal
tissue arrangement and cell structure. Often
such cells revert back to normal behavior, but
occasionally, they gradually become malignant.
The most severe cases of dysplasia are referred
to as "carcinoma in situ." In Latin, the term
"in situ" means "in place", so carcinoma in situ
refers to an uncontrolled growth of cells that
remains in the original location and shows no
propensity to invade other tissues.
Nevertheless, carcinoma in situ may develop into
an invasive malignancy and is usually removed
surgically, if possible.
Heredity
Most forms of cancer are "sporadic", and have no
basis in heredity. There are, however, a number
of recognized syndromes of cancer with a
hereditary component. Examples are:
·
certain inherited mutations in the genes BRCA1
and BRCA2 are associated with an elevated risk
of breast cancer and ovarian cancer
·
tumors of various endocrine organs in multiple
endocrine neoplasia (MEN types 1, 2a, 2b)
·
Li-Fraumeni syndrome (various tumors such as
osteosarcoma, breast cancer, soft-tissue
sarcoma, brain tumors) due to mutations of p53
· Turcot
syndrome (brain tumors and colonic polyposis)
·
Familial adenomatous polyposis an inherited
mutation of the APC gene that leads to
early onset of colon carcinoma.
·
Retinoblastoma in young children is an inherited
cancer.
Treatment
of cancer
Cancer can be treated by surgery, chemotherapy,
radiation therapy, immunotherapy or other
methods. The choice of therapy depends upon the
location and grade of the tumor and the stage of
the disease, as well as the general state of the
patient (performance status). A number of
experimental cancer treatments are also under
development.
Complete removal of the cancer without damage to
the rest of the body is the goal of treatment.
Sometimes this can be accomplished by surgery,
but the propensity of cancers to invade adjacent
tissue or to spread to distant sites by
microscopic metastasis often limits its
effectiveness. The effectiveness of chemotherapy
is often limited by toxicity to other tissues in
the body. Radiation can also cause damage to
normal tissue.
Because "cancer" refers to a class of diseases,
it is unlikely that there will ever be a single
"cure for cancer" any more than there will be a
single treatment for all infectious diseases.
Surgery
If the tumor is localized, surgery is often the
preferred treatment. Example procedures include
mastectomy for breast cancer and prostatectomy
for prostate cancer. The goal of the surgery can
be either the removal of only the tumor, or the
entire organ. Since a single cancer cell can
grow into a sizable tumor, removing only the
tumor leads to a greater chance of recurrence. A
margin of healthy tissue is often resected to
make sure all cancerous tissue is removed.
In addition to removal of the primary tumor,
surgery is often necessary for staging, e.g.
determining the extent of the disease and
whether there has been metastasis to regional
lymph nodes. Staging determines the prognosis
and the need for adjuvant therapy.
Occasionally, surgery is necessary to control
symptoms, such as spinal cord compression or
bowel obstruction. This is referred to as
palliative treatment.
Chemotherapy
Chemotherapy is the treatment of cancer with
drugs ("anticancer drugs") that can destroy
cancer cells. It interferes with cell division
in various possible ways, e.g. with the
duplication of DNA or the separation of newly
formed chromosomes. Most forms of chemotherapy
target all rapidly dividing cells and are not
specific for cancer cells. Hence, chemotherapy
has the potential to harm healthy tissue,
especially those tissues that have a high
replacement rate (e.g. intestinal lining). These
cells usually repair themselves after
chemotherapy.
Because some drugs work better together than
alone, two or more drugs are often given at the
same time. This is called "combination
chemotherapy"; most chemotherapy regimens are
given in a combination.
A novel technique involves taking samples of the
patient's tissue before chemotherapy. These
tissues samples are screened to ensure they do
not contain cancerous cells. The samples are
expanded using tissue engineering techniques,
and are then re-implanted following high dose
chemotherapy in order to recolonise the damaged
and somewhat destroyed tissue. A variation upon
this method uses allogenic samples (samples
donated by a different donor) instead of the
patient's own tissue.
Immunotherapy
Immunotherapy is the use of immune mechanisms
against tumors. These are used in various forms
of cancer, such as breast cancer
(trastuzumab/Herceptin®) but also in leukemia (gemtuzumab
ozogamicin/Mylotarg®). The agents are
monoclonal antibodies directed against proteins
that are characteristic to the cells of the
cancer in question, or cytokines that modulate
the immune system's response.
Radiation
therapy
Radiation therapy (also called radiotherapy,
X-ray therapy, or irradiation) is the use of a
certain type of energy (called ionizing
radiation) to kill cancer cells and shrink
tumors. Radiation therapy injures or destroys
cells in the area being treated (the "target
tissue") by damaging their genetic material,
making it impossible for these cells to continue
to grow and divide. Although radiation damages
both cancer cells and normal cells, most normal
cells can recover from the effects of radiation
and function properly. The goal of radiation
therapy is to damage as many cancer cells as
possible, while limiting harm to nearby healthy
tissue.
Radiation therapy may be used to treat almost
every type of solid tumor, including cancers of
the brain, breast, cervix, larynx, lung,
pancreas, prostate, skin, spine, stomach,
uterus, or soft tissue sarcomas. Radiation can
also be used to treat leukemia and lymphoma
(cancers of the blood-forming cells and
lymphatic system, respectively). Radiation dose
to each site depends on a number of factors,
including the type of cancer and whether there
are tissues and organs nearby that may be
damaged by radiation.
Hormonal
suppression
The growth of nearly all tissues, including
cancers, can be accelerated or inhibited by
providing or blocking certain hormones. This
allows an additional method of treatment for
many cancers. Common examples of
hormone-sensitive tumors include certain types
of breast, prostate, and thyroid cancers.
Removing or blocking estrogen, testosterone, or
TSH, respectively, is often an important
additional treatment.
Treatment
trials
Clinical trials, also called research studies,
test new treatments in people with cancer. The
goal of this research is to find better ways to
treat cancer and help cancer patients. Clinical
trials test many types of treatment such as new
drugs, new approaches to surgery or radiation
therapy, new combinations of treatments, or new
methods such as gene therapy.
A clinical trial is one of the final stages of a
long and careful cancer research process. The
search for new treatments begins in the
laboratory, where scientists first develop and
test new ideas. If an approach seems promising,
the next step may be testing a treatment in
animals to see how it affects cancer in a living
being and whether it has harmful effects. Of
course, treatments that work well in the lab or
in animals do not always work well in people.
Studies are done with cancer patients to find
out whether promising treatments are safe and
effective.
Patients who take part may be helped personally
by the treatment(s) they receive. They get
up-to-date care from cancer experts, and they
receive either a new treatment being tested or
the best available standard treatment for their
cancer. Of course, there is no guarantee that a
new treatment being tested or a standard
treatment will produce good results. New
treatments also may have unknown risks, but if a
new treatment proves effective or more effective
than standard treatment, study patients who
receive it may be among the first to benefit.
Complementary
and alternative medicine
Complementary and alternative medicine (CAM)
treatments are the diverse group of medical and
health care systems, practices, and products
that are not presently considered to be
effective by the standards of conventional
medicine. Some non-conventional treatment
methods are used to "complement" conventional
treatment, to provide comfort or lift the
spirits of the patient, while others are offered
as alternatives to be used instead of
conventional treatments in hope of curing the
cancer.
Common
complementary
measures
include prayer or psychological approaches such
as "imaging." Many people feel these approaches
benefit them, but most have not been
scientifically proven and therefore face
scepticism. Other complementary approaches
include traditional medicine like Traditional
Chinese Medicine.
A wide range of alternative treatments have been
offered for cancer over the last century. The
appeal of alternative cures arises from the
daunting risks, costs, or potential side effects
of many conventional treatments, or in the
limited prospect for cure. Proponents of these
therapies are unable or unwilling to demonstrate
effectiveness by conventional criteria.
Alternative treatments have included special
diets or dietary supplements (e.g., the "grape
diet" or megavitamin therapy), electrical
devices (e.g., "zappers"), specially formulated
compounds (e.g., laetrile), unconventional use
of conventional drugs (e.g., insulin), purges or
enemas, or physical manipulations of the body.
Some of these treatments meet all the criteria
for fraud or magic. Collectively they are
referred to by skeptics as
cancer quackery. An extensive,
explanatory catalog of these treatments is
available at Quack watch [1]. Almost all
physicians recommend against using these
modalities as sole treatment for potentially
fatal conditions such as cancer.
Epidemiology
In some Western countries, such as the USA1
and the UK2, cancer is overtaking
cardiovascular disease as the leading cause of
death. In many Third World countries cancer
incidence (insofar as this can be measured)
appears much lower, most likely because of the
higher death rates due to infectious disease or
injury. With the increased control over malaria
and tuberculosis in some Third World countries,
incidence of cancer is expected to rise; this is
termed the iceberg phenomenon in epidemiological
terminology.
Cancer epidemiology closely mirrors risk factor
spread in various countries. Hepatocellular
carcinoma (liver cancer) is rare in the West but
is the main cancer in
China and neighbouring countries,
most likely due to the endemic presence of
hepatitis B and aflatoxin in that population.
Similarly, with tobacco smoking becoming more
common in various Third World countries, lung
cancer incidence has increased in a parallel
fashion.
Prevention
Cancer prevention is defined as active measures
to decrease the incidence of cancer. This can be
accomplished by avoiding carcinogens or altering
their metabolism, pursuing a lifestyle or diet
that modifies cancer-causing factors and/or
medical intervention (chemoprevention, treatment
of premalignant lesions).
Much of the promise for cancer prevention comes
from observational epidemiologic studies that
show associations between modifiable life style
factors or environmental exposures and specific
cancers. Evidence is now emerging from
randomized controlled trials designed to test
whether interventions suggested by the
epidemiologic studies, as well as leads based on
laboratory research, actually result in reduced
cancer incidence and mortality.
Examples of modifiable cancer risk include
alcohol consumption (associated with increased
risk of oral, esophageal, breast, and other
cancers), physical inactivity (associated with
increased risk of colon, breast, and possibly
other cancers), and being overweight (associated
with colon, breast, endometrial, and possibly
other cancers). Based on epidemiologic evidence,
it is now thought that avoiding excessive
alcohol consumption, being physically active,
and maintaining recommended body weight may all
contribute to reductions in risk of certain
cancers; however, compared with tobacco
exposure, the magnitude of effect is modest or
small and the strength of evidence is often
weaker. Other lifestyle and environmental
factors known to affect cancer risk (either
beneficially or detrimentally) include certain
sexual and reproductive practices, the use of
exogenous hormones, exposure to ionizing
radiation and ultraviolet radiation, certain
occupational and chemical exposures, and
infectious agents.
Diet and cancer
The consensus on diet and cancer is that obesity
increases the risk of developing cancer.
Particular dietary practices often explain
differences in cancer incidence in different
countries (e.g. gastric cancer is more common in
Japan, while colon cancer is more common in the
United States). Studies have shown that
immigrants develop the risk of their new
country, suggesting a link between diet and
cancer rather than a genetic basis.
Despite frequent reports of particular
substances (including foods) having a beneficial
or detrimental effect on cancer risk, few of
these have an established link to cancer. These
reports are often based on studies in cultured
cell media or animals. Public health
recommendations cannot be made on the basis of
these studies until they have been validated in
an observational (or occasionally a prospective
interventional) trial in humans.
The case of beta-carotene provides an example of
the necessity of randomized clinical trials.
Epidemiologists studying both diet and serum
levels observed that high levels of
beta-carotene, a precursor to vitamin A, were
associated with a protective effect, reducing
the risk of cancer. This effect was particularly
strong in lung cancer. This hypothesis led to a
series of large randomized trials conducted in
both Finland and the United States (CARET study)
during the 1980s and 1990s. This study provided
about 80,000 smokers or former smokers with
daily supplements of beta-carotene or placebos.
Contrary to expectation, these tests found no
benefit of beta-carotene supplementation in
reducing lung cancer incidence and mortality. In
fact, the risk of lung cancer was slightly, but
significantly, increased in smokers, leading to
an early termination of the study.
Other chemoprevention agents
Daily use of tamoxifen, a selective estrogen
receptor modulator, for up to 5 years, has been
demonstrated to reduce the risk of developing
breast cancer in high-risk women by about 50%.
Cis-retinoic acid also has been shown to reduce
risk of second primary tumors among patients
with primary head and neck cancer. Finasteride,
a 5-alpha reductase inhibitor, has been shown to
lower the risk of prostate cancer. Other
examples of drugs that show promise for
chemoprevention include COX-2 inhibitors (which
inhibit a cyclooxygenase enzyme involved in the
synthesis of proinflammatory prostaglandins).
Cancer vaccines
Considerable research effort is now devoted to
the development of vaccines (to prevent
infection by oncogenic infectious agents, as
well as to mount an immune response against
cancer-specific epitopes) and to potential
venues for gene therapy for individuals with
genetic mutations or polymorphisms that put them
at high risk of cancer. No cancer vaccines are
presently in use, and most of the research is
still in its initial stages.
Genetic testing
Genetic testing for high-risk individuals, with
enhanced surveillance, chemoprevention, or
risk-reducing surgery for those who test
positive, is already available for certain
cancer-related genetic mutations.
Coping with cancer
Many local organizations offer a variety of
practical and support services to people with
cancer. Support can take the form of support
groups, counselling, advice, financial
assistance, transportation to and from
treatment, or information about cancer.
Neighbourhood organizations, local health care
providers, or area hospitals are a good place to
start looking.
While some people are reluctant to seek
counselling, studies show that having someone to
talk to reduces stress and helps people both
mentally and physically. Counselling can also
provide emotional support to cancer patients and
help them better understand their illness.
Different types of counselling include
individual, group, family, self-help (sometimes
called peer counselling), bereavement,
patient-to-patient, and sexuality.
Many governmental and charitable organizations
have been established to help patients cope with
cancer. These organizations often are involved
in cancer prevention, cancer treatment, and
cancer research. Examples include: American
Cancer Society, BC Cancer Agency, Macmillan
Cancer Relief UK, Cancer Research UK, Canadian
Cancer Society, International Agency for
Research on Cancer and the National Cancer
Institute (US).
Social impact
Cancer has a reputation for being a deadly
disease. While this certainly applies to certain
particular types, this is otherwise a
generalization. Some types of cancer have a
prognosis that is substantially better than
non-malignant diseases such as heart failure and
stroke.
Progressive and disseminated malignant disease
has a substantial impact on a cancer patient's
quality of life, and many cancer treatments
(such as chemotherapy) may have severe
side-effects. In the advanced stages of cancer,
many patients need extensive care, affecting
family members and friends. Palliative care
solutions may include permanent or "respite"
hospice nursing.
Cancer research
Cancer research is the intense scientific effort
to understand disease processes and discover
possible therapies. While understanding of
cancer has increased exponentially since the
last decades of the 20th century, radically new
therapies are only discovered and introduced
gradually.
Inhibitors of tyrosine kinases (imatinib and
gefitinib) in the late 1990s were considered a
major breakthrough; these interfere specifically
with tumor-specific proteins. Monoclonal
antibodies have proven to be another major step
in oncological treatment.
