Cancer (medical term:
malignant neoplasm) is a
class of
diseases in which a group of
cells display
uncontrolled
growth (
division beyond the
normal limits),
invasion (intrusion on and destruction of
adjacent tissues), and sometimes
metastasis (spread to other locations in the
body via lymph or blood). These three malignant properties of
cancers differentiate them from
benign
tumors, which are self-limited, and do not invade or
metastasize. Most cancers form a
tumor but
some, like
leukemia, do not. The branch of
medicine concerned with the study, diagnosis, treatment, and
prevention of cancer is
oncology.
Cancer may affect people at all ages, even
fetuses, but the risk for most varieties increases
with age. Cancer causes about 13% of
all
human deaths. According to the
American Cancer Society,
7.6 million people died from cancer in the world during 2007.
Cancers can affect all animals.
Nearly all cancers are caused by abnormalities in the
genetic material of the
transformed cells. These
abnormalities may be due to the effects of
carcinogens, such as
tobacco smoke,
radiation,
chemicals, or
infectious
agents. Other cancer-promoting genetic abnormalities may be
randomly acquired through errors in
DNA
replication, or are
inherited,
and thus present in all cells from birth. The
heritability of cancers is usually affected by
complex interactions between carcinogens and the host's
genome. New aspects of the genetics of cancer
pathogenesis, such as
DNA
methylation, and
microRNAs are
increasingly recognized as important.
Genetic abnormalities found in cancer typically affect two general
classes of genes. Cancer-promoting
oncogenes are typically activated in cancer
cells, giving those cells new properties, such as hyperactive
growth and division, protection against
programmed cell death, loss of respect
for normal tissue boundaries, and the ability to become established
in diverse tissue environments.
Tumor suppressor genes are then
inactivated in cancer cells, resulting in the loss of normal
functions in those cells, such as accurate DNA replication, control
over the
cell cycle, orientation and
adhesion within tissues, and interaction with protective cells of
the
immune system.
Diagnosis usually requires the
histologic
examination of a tissue
biopsy specimen by a
pathologist, although the
initial indication of malignancy can be symptoms or
radiographic imaging abnormalities. Most
cancers can be treated and some cured, depending on the specific
type, location, and
stage. Once
diagnosed, cancer is usually treated with a combination of
surgery,
chemotherapy
and
radiotherapy. As research
develops, treatments are becoming more specific for different
varieties of cancer. There has been significant progress in the
development of
targeted therapy
drugs that act specifically on detectable molecular abnormalities
in certain tumors, and which minimize damage to normal cells. The
prognosis of cancer patients is most influenced by the type of
cancer, as well as the
stage, or
extent of the disease. In addition,
histologic grading
and the presence of specific molecular markers can also be useful
in establishing prognosis, as well as in determining individual
treatments.
Glossary
The following closely related terms may be used to designate
abnormal growths:
- Tumor or tumour:
originally, it meant any abnormal swelling, lump or mass. In
current English, however, the word tumor has become synonymous with
neoplasm, specifically solid neoplasm. Note that some neoplasms,
such as leukemia, do not form tumors.
- Neoplasm: the
scientific term to describe an abnormal proliferation of
genetically altered cells. Neoplasms can be benign or malignant:
- Malignant neoplasm or malignant
tumor: synonymous with cancer.
- Benign neoplasm or benign tumor: a tumor (solid neoplasm)
that stops growing by itself, does not invade other tissues and
does not form metastases.
- Invasive tumor is another synonym of
cancer. The name refers to invasion of surrounding
tissues.
- Pre-malignancy, pre-cancer or
non-invasive tumor: A neoplasm that is not
invasive but has the potential to progress to cancer (become
invasive) if left untreated. These lesions are, in order of
increasing potential for cancer, atypia,
dysplasia and carcinoma in situ.
The following terms can be used to describe a cancer:
- Screening: a test done on healthy people to
detect tumors before they become apparent. A mammogram is a screening test.
- Diagnosis: the confirmation of the cancerous
nature of a lump. This usually requires a biopsy or removal of the tumor by surgery, followed by examination by a pathologist.
- Surgical excision: the removal of a tumor by a
surgeon.
- Surgical margins: the evaluation by a pathologist of the edges of the tissue
removed by the surgeon to determine if the tumor was removed
completely ("negative margins") or if tumor was left behind
("positive margins").
- Grade: a number (usually on a scale of 3)
established by a pathologist to
describe the degree of resemblance of the tumor to the surrounding
benign tissue.
- Stage: a number (usually on a scale of 4)
established by the oncologist to describe
the degree of invasion of the body by the tumor.
- Recurrence: new tumors that appear at the site
of the original tumor after surgery.
- Metastasis: new tumors that appear far from
the original tumor.
- Median survival time: a period of time, often
measured in months or years, over which 50% of the cancer patients
are expected to be alive.
- Transformation: the concept that a low-grade
tumor transforms to a high-grade tumor over time. Example: Richter's transformation.
- Chemotherapy: treatment with drugs.
- Radiation therapy: treatment with
radiations.
- Adjuvant therapy: treatment, either
chemotherapy or radiation therapy, given after surgery to kill the
remaining cancer cells.
- Prognosis: the probability of cure after the
therapy. It is usually expressed as a probability of survival five years after diagnosis.
Alternatively, it can be expressed as the number of years when 50%
of the patients are still alive. Both numbers are derived from
statistics accumulated with hundreds of similar patients to give a
Kaplan-Meier curve.
- Cure: A cancer patient is "cured" if 95% of
treated patients live a certain period of time after the date of
their diagnosis of cancer. For example in the case of Hodgkin's
disease this period of time is 10 years, whereas for Burkitt's
lymphoma this period would be 1 year. The phrase "cure" used in
oncology is based upon the statistical concept of a median survival
time and disease-free median survival time.
Classification
Cancers are classified by the
type of
cell that resembles the tumor and, therefore, the tissue
presumed to be the origin of the tumor. These are the histology and
the location, respectively. Examples of general categories include:
- Carcinoma: Malignant
tumors derived from epithelial cells.
This group represents the most common cancers, including the common
forms of breast, prostate, lung
and colon cancer.
- Sarcoma: Malignant
tumors derived from connective
tissue, or mesenchymal cells.
- Lymphoma and
leukemia: Malignancies
derived from hematopoietic (blood-forming)
cells
- Germ cell
tumor: Tumors derived from totipotent cells. In adults most often found in
the testicle and ovary; in fetuses, babies, and young children most
often found on the body midline, particularly at the tip of the
tailbone; in horses most often found at the poll (base of the
skull).
- Blastic tumor or blastoma: A tumor (usually malignant)
which resembles an immature or embryonic tissue. Many of these
tumors are most common in children.
Malignant tumors (cancers) are usually named using
-carcinoma,
-sarcoma or
-blastoma as a suffix, with the Latin or Greek
word for the organ of origin as the root. For instance, a cancer of
the liver is called
hepatocarcinoma; a cancer of the fat
cells is called
liposarcoma. For common cancers, the
English organ name is used. For instance, the most common type of
breast cancer is called
ductal
carcinoma of the breast or
mammary ductal carcinoma.
Here, the adjective
ductal refers to the appearance of the
cancer under the microscope, resembling normal breast ducts.
Benign tumors (which are not cancers)
are named using
-oma as a suffix with the organ
name as the root. For instance, a benign tumor of the smooth muscle
of the uterus is called
leiomyoma (the common name of this
frequent tumor is
fibroid). Unfortunately, some cancers
also use the
-oma suffix, examples being
melanoma and
seminoma.
Signs and symptoms
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Symptoms of cancer metastasis depend
on the location of the tumor.
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 (yellowing the eyes and skin).
- 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
often not the first symptom.
- Systemic symptoms: weight
loss, poor appetite, fatigue 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 symptom 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.
Causes
Cancer is a diverse class of diseases which differ widely in their
causes and biology. Any organism, even
plants, can acquire cancer. Nearly all known cancers
arise gradually, as errors build up in the cancer cell and its
progeny (see
mechanisms section
for common types of errors).
Anything which replicates (our cells) will
probabilistically suffer from errors
(mutations). Unless
error
correction and prevention is properly carried out, the errors
will survive, and might be passed along to
daughter cells. Normally, the body safeguards
against cancer via numerous methods, such as:
apoptosis, helper molecules (some DNA
polymerases), possibly
senescence, etc.
However these error-correction methods often fail in small ways,
especially in environments that make errors more likely to arise
and propagate. For example, such environments can include the
presence of disruptive substances called
carcinogens, or periodic injury (physical, heat,
etc.), or environments that cells did not evolve to withstand, such
as
hypoxia (see subsections).
Cancer is thus a
progressive disease, and these
progressive errors slowly accumulate until a cell begins to act
contrary to its function in the animal.
The errors which cause cancer are often
self-amplifying,
eventually compounding at an exponential rate. For example:
- A mutation in the error-correcting machinery of a cell might
cause that cell and its children to accumulate errors more
rapidly
- A mutation in signaling (endocrine)
machinery of the cell can send error-causing signals to nearby
cells
- A mutation might cause cells to become neoplastic, causing them to migrate and disrupt
more healthy cells
- A mutation may cause the cell to become immortal (see telomeres), causing them to disrupt healthy cells
forever
Thus cancer often explodes in something akin to a
chain reaction caused by a few errors, which
compound into more severe errors. Errors which produce more errors
are effectively the root cause of cancer, and also the reason that
cancer is so hard to treat: even if there were 10,000,000,000
cancerous cells and one killed all but 10 of those cells, those
cells (and other error-prone precancerous cells) could still
self-replicate or send error-causing signals to other cells,
starting the process over again. This rebellion-like scenario is an
undesirable
survival of the
fittest, where the driving forces of
evolution itself work against the body's design
and enforcement of order. In fact, once cancer has begun to
develop, this same force continues to drive the progression of
cancer towards more invasive stages, and is called
clonal evolution.
Research about cancer causes often
falls into the following categories:
- Agents (e.g. viruses) and events (e.g. mutations) which cause
or facilitate genetic changes in cells destined to become
cancer.
- The precise nature of the genetic damage, and the genes which
are affected by it.
- The consequences of those genetic changes on the biology of the
cell, both in generating the defining properties of a cancer cell,
and in facilitating additional genetic events which lead to further
progression of the cancer.
Mutation: chemical carcinogens
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The incidence of lung cancer is highly
correlated with smoking.
Cancer pathogenesis is traceable back to
DNA mutations that impact cell growth and
metastasis. Substances that cause
DNA
mutations are known as mutagens, and mutagens that cause
cancers are known as carcinogens. Particular substances have been
linked to specific types of cancer.
Tobacco smoking is associated with many
forms of cancer, and causes 90% of
lung
cancer. Prolonged exposure to
asbestos
fibers is associated with
mesothelioma.
Many
mutagens are also
carcinogens, but some carcinogens are not
mutagens.
Alcohol is an example of a
chemical carcinogen that is not a mutagen. Such chemicals may
promote cancers through stimulating the rate of cell division.
Faster rates of replication leaves less time for repair enzymes to
repair damaged DNA during
DNA
replication, increasing the likelihood of a mutation.
Decades of research has demonstrated the link between
tobacco use and cancer in the lung, larynx, head,
neck, stomach, bladder, kidney, oesophagus and pancreas. Tobacco
smoke contains over fifty known carcinogens, including
nitrosamines and
polycyclic aromatic
hydrocarbons. Tobacco is responsible for about one in three of
all cancer deaths in the developed world, and about one in five
worldwide. Indeed,
lung cancer death
rates in the United States have mirrored
smoking patterns, with increases in smoking
followed by dramatic increases in lung cancer death rates and, more
recently, decreases in smoking followed by decreases in lung cancer
death rates in men. However, the numbers of smokers worldwide is
still rising, leading to what some organizations have described as
the
tobacco epidemic.
Mutation: ionizing radiation
Sources of
ionizing radiation,
such as
radon gas, can cause cancer. Prolonged
exposure to
ultraviolet
radiation from the
sun can lead to
melanoma and other skin malignancies.
Non-ionizing radio frequency radiation from
mobile phones and other similar
RF sources has also been proposed as a cause
of cancer, but there is currently little established evidence of
such a link.
Viral or bacterial infection
Some cancers can be caused by
infection
with
pathogens. Many cancers originate from
a
viral infection; this is especially true in
animals such as
birds, but also in
humans, as viruses are responsible for 15% of human
cancers worldwide. The main viruses associated with human cancers
are
human papillomavirus,
hepatitis B and
hepatitis C virus,
Epstein-Barr virus, and
human T-lymphotropic virus.
Experimental and epidemiological data imply a causative role for
viruses and they appear to be the second most important risk factor
for cancer development in humans, exceeded only by tobacco usage.
The mode of virally-induced tumors can be divided into two,
acutely-transforming or
slowly-transforming. In
acutely transforming viruses, the virus carries an overactive
oncogene called viral-oncogene (v-onc), and the infected cell is
transformed as soon as v-onc is expressed. In contrast, in
slowly-transforming viruses, the virus genome is inserts near a
proto-oncogene in the host genome. The viral
promoter or other transcription regulation elements
then cause overexpression of that proto-oncogene. This induces
uncontrolled cell division. Because the site of insertion is not
specific to proto-oncogenes and the chance of insertion near any
proto-oncogene is low, slowly-transforming viruses will cause
tumors much longer after infection than the acutely-transforming
viruses.
Hepatitis viruses, including
hepatitis B
and
hepatitis C, can induce a chronic
viral infection that leads to
liver cancer in 0.47% of
hepatitis B patients per year (especially in
Asia, less so in North America), and in 1.4% of
hepatitis C carriers per year. Liver cirrhosis,
whether from chronic viral hepatitis infection or alcoholism, is
associated with the development of
liver cancer, and the combination
of cirrhosis and viral hepatitis presents the highest risk of
liver cancer development.
Worldwide,
liver cancer is
one of the most common, and most deadly, cancers due to a huge
burden of
viral hepatitis
transmission and disease.
Advances in cancer research have made a vaccine designed to prevent
cancer available. In 2006, the
U.S. Food and Drug
Administration approved a
human papilloma virus vaccine, called
Gardasil. The vaccine protects against four
HPV types, which together cause 70% of cervical cancers and 90% of
genital warts. In March 2007, the US
Centers for Disease
Control and Prevention (CDC)
Advisory Committee
on Immunization Practices (ACIP) officially recommended that
females aged 11–12 receive the vaccine, and indicated that females
as young as age 9 and as old as age 26 are also candidates for
immunization.
In addition to viruses, researchers have noted a connection between
bacteria and certain cancers. The
most prominent example is the link between chronic infection of the
wall of the stomach with
Helicobacter pylori and
gastric cancer. Although only a minority of
those infected with
Helicobacter go on to develop cancer,
since this pathogen is quite common it is probably responsible for
the majority of these cancers.
Hormonal imbalances
Some hormones can act in a similar manner to non-mutagenic
carcinogens in that they may stimulate excessive cell growth. A
well-established example is the role of
hyperestrogenic states in promoting
endometrial cancer.
Immune system dysfunction
HIV is associated with a number of malignancies,
including
Kaposi's sarcoma,
non-Hodgkin's lymphoma, and
HPV-associated malignancies such as
anal cancer and
cervical cancer.
AIDS-defining illnesses have long included these
diagnoses. The increased incidence of malignancies in HIV patients
points to the breakdown of immune surveillance as a possible
etiology of cancer. Certain other immune deficiency states (e.g.
common variable
immunodeficiency and
IgA
deficiency) are also associated with increased risk of
malignancy.
Heredity
Most forms of cancer are
sporadic, meaning that there is
no inherited cause of the cancer. There are, however, a number of
recognised
syndromes where there is an
inherited predisposition to cancer, often due to a defect in a gene
that
protects against tumor
formation. Famous 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.
- Hereditary
nonpolyposis colorectal cancer (HNPCC, also known as Lynch
syndrome) can include familial cases of colon cancer, uterine cancer, gastric cancer, and ovarian cancer, without a preponderance of
colon polyps.
- Retinoblastoma, when occurring in
young children, is due to a hereditary mutation in the
retinoblastoma gene.
- Down syndrome patients, who have
an extra chromosome 21, are known to
develop malignancies such as leukemia and
testicular cancer, though the
reasons for this difference are not well understood.
Other causes
Excepting the rare transmissions that occur with pregnancies and
only a marginal few organ donors, cancer is generally not a
transmissible disease. The main reason for this is tissue graft
rejection caused by
MHC incompatibility. In humans and other
vertebrates, the immune system uses MHC antigens to differentiate
between "self" and "non-self" cells because these antigens are
different from person to person. When non-self antigens are
encountered, the immune system reacts against the appropriate cell.
Such reactions may protect against tumour cell engraftment by
eliminating implanted cells. In the United States, approximately
3,500 pregnant women have a malignancy annually, and transplacental
transmission of
acute leukaemia,
lymphoma,
melanoma
and
carcinoma from mother to fetus has
been observed. The development of donor-derived tumors from organ
transplants is exceedingly rare. The main cause of organ transplant
associated tumors seems to be malignant melanoma, that was
undetected at the time of organ harvest, though other cases exist.
In fact, cancer from one organism will usually grow in another
organism of that species, as long as they share the same
histocompatibility genes, proven using
mice; however this would never happen in a real-world setting
except as described above.
In non-humans, a few types of cancer have been found to be caused
by transmission of the tumor cells themselves. This phenomenon is
seen in dogs with
Sticker's
sarcoma, also known as canine transmissible venereal tumor, as
well as
Devil facial tumour
disease in
Tasmanian
devils.
Pathophysiology
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Cancers are caused by a series of
mutations.
Each mutation alters the behavior of the cell somewhat.
Cancer is fundamentally a disease of regulation of tissue growth.
In order for a normal cell to
transform into a cancer cell,
genes which regulate cell growth and
differentiation must be altered. Genetic changes can occur at many
levels, from gain or loss of entire chromosomes to a mutation
affecting a
single DNA
nucleotide. There are two broad categories of genes which are
affected by these changes.
Oncogenes may be
normal genes which are expressed at inappropriately high levels, or
altered genes which have novel properties. In either case,
expression of these genes promotes the malignant phenotype of
cancer cells.
Tumor suppressor
genes are genes which inhibit cell division, survival, or other
properties of cancer cells. Tumor suppressor genes are often
disabled by cancer-promoting genetic changes. Typically, changes in
many genes are required to transform a normal cell into a cancer
cell.
There is a diverse classification scheme for the various genomic
changes which may contribute to the generation of cancer cells.
Most of these changes are
mutations, or
changes in the
nucleotide sequence of
genomic DNA.
Aneuploidy, the presence of
an abnormal number of chromosomes, is one genomic change which is
not a mutation, and may involve either gain or loss of one or more
chromosomes through errors in
mitosis.
Large-scale mutations involve the deletion or gain of a portion of
a chromosome.
Genomic
amplification occurs when a cell gains many copies (often 20 or
more) of a small chromosomal locus, usually containing one or more
oncogenes and adjacent genetic material.
Translocation occurs when two
separate chromosomal regions become abnormally fused, often at a
characteristic location. A well-known example of this is the
Philadelphia chromosome, or
translocation of chromosomes 9 and 22, which occurs in
chronic myelogenous leukemia,
and results in production of the
BCR-
abl fusion protein, an oncogenic
tyrosine kinase.
Small-scale mutations include point mutations, deletions, and
insertions, which may occur in the
promoter
of a gene and affect its
expression,
or may occur in the gene's
coding
sequence and alter the function or stability of its
protein product. Disruption of a single gene may
also result from
integration of genomic
material from a
DNA virus or
retrovirus, and such an event may also result in
the expression of viral oncogenes in the affected cell and its
descendants.
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
pre-malignant lesions). The
epidemiological concept of "prevention" is
usually defined as either
primary
prevention, for people who have not been diagnosed with a
particular disease, or
secondary
prevention, aimed at reducing recurrence or complications of a
previously diagnosed illness.
Modifiable ("lifestyle") risk factors
The vast majority of cancer risk factors are environmental or
lifestyle-related in nature, leading to the claim that cancer is a
largely preventable disease. Examples of modifiable cancer risk
factors include
alcohol
consumption (associated with increased risk of oral, esophageal,
breast, and other cancers), smoking (although 20% of women with
lung cancer have never smoked, versus 10% of men), physical
inactivity (associated with increased risk of colon, breast, and
possibly other cancers), and being
overweight /
obese
(associated with colon, breast, endometrial, and possibly other
cancers). Based on epidemiologic evidence, it is now thought that
avoiding excessive alcohol consumption may 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 sexually transmitted
diseases (such as those conveyed by the
human papillomavirus), the use of
exogenous hormones, exposure to
ionizing radiation and
ultraviolet radiation, and certain occupational
and chemical exposures.
Every year, at least 200,000 people die worldwide from cancer
related to their workplace. Millions of workers run the risk of
developing cancers such as
lung cancer
and
mesothelioma from inhaling asbestos
fibers and tobacco smoke, or
leukemia from
exposure to
benzene at their workplaces.
Currently, most cancer deaths caused by occupational risk factors
occur in the developed world. It is estimated that approximately
20,000 cancer deaths and 40,000 new cases of cancer each year in
the U.S. are attributable to occupation.
Diet
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. In this example the preceding consideration of
Haplogroups are excluded). Studies have
shown that immigrants develop the risk of their new country, often
within one generation, suggesting a substantial link between diet
and cancer. Whether reducing obesity in a population also reduces
cancer incidence is unknown.
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.
Proposed dietary interventions for primary cancer risk reduction
generally gain support from epidemiological association studies.
Examples of such studies include reports that reduced meat
consumption is associated with decreased risk of colon cancer,and
reports that consumption of coffee is associated with a reduced
risk of liver cancer. Studies have linked consumption of grilled
meat to an increased risk of
stomach
cancer,
colon cancer,
breast cancer, and
pancreatic cancer, a phenomenon which
could be due to the presence of carcinogens such as
benzopyrene in foods cooked at high
temperatures.
A 2005
secondary prevention
study showed that consumption of a plant-based diet and lifestyle
changes resulted in a reduction in cancer markers in a group of men
with prostate cancer who were using no conventional treatments at
the time.These results were amplified by a 2006 study in which over
2,400 women were studied, half randomly assigned to a normal diet,
the other half assigned to a diet containing less than 20% calories
from fat. The women on the low fat diet were found to have a
markedly lower risk of breast cancer recurrence, in the interim
report of December, 2006.
Recent studies have also demonstrated potential links between some
forms of cancer and high consumption of refined sugars and other
simple carbohydrates. Although the degree of correlation and the
degree of causality is still debated, some organizations have in
fact begun to recommend reducing intake of refined sugars and
starches as part of their cancer prevention regimens.
In November 2007, the
American Institute for
Cancer Research (AICR), in conjunction with the
World Cancer Research Fund
(WCRF), published
Food, Nutrition, Physical Activity and the Prevention of Cancer: a
Global Perspective, "the most current and comprehensive
analysis of the literature on diet, physical activity and cancer".
The WCRF/AICR Expert Report lists 10 recommendations that people
can follow to help reduce their risk of developing cancer,
including the following dietary guidelines: (1) reducing intake of
foods and drinks that promote weight gain, namely energy-dense
foods and sugary drinks, (2) eating mostly foods of plant origin,
(3) limiting intake of red meat and avoiding processed meat, (4)
limiting consumption of alcoholic beverages, and (5) reducing
intake of salt and avoiding mouldy cereals (grains) or pulses
(legumes).
Some mushrooms offer an anti-cancer effect, which is thought to be
linked to their ability to up-regulate the immune system. Some
mushrooms known for this effect include,
Reishi,
Agaricus
blazei,
[15513],
Maitake,
[15514] and
Trametes versicolor[15515]. Research suggests the compounds in
medicinal mushrooms most responsible for
up-regulating the immune system and providing an anti-cancer
effect, are a diverse collection of
polysaccharide compounds, particularly
beta-glucans. Beta-glucans are known as
"biological response modifiers", and their ability to activate the
immune system is well documented. Specifically, beta-glucans
stimulate the
innate branch of
the immune system. Research has shown beta-glucans have the ability
to stimulate
macrophage,
NK cells,
T cells, and
immune system
cytokines. The mechanisms in
which beta-glucans stimulate the immune system is only partially
understood. One mechanism in which beta-glucans are able to
activate the immune system, is by interacting with the
Macrophage-1 antigen (
CD18)
receptor on immune
cells.
Vitamins
The idea that cancer can be prevented through vitamin
supplementation stems from early observations correlating human
disease with vitamin deficiency, such as
pernicious anemia with
vitamin B12 deficiency, and
scurvy with
Vitamin C
deficiency. This has largely not been proven to be the case with
cancer, and vitamin supplementation is largely not proving
effective in preventing cancer. The cancer-fighting components of
food are also proving to be more numerous and varied than
previously understood, so patients are increasingly being advised
to consume fresh, unprocessed fruits and vegetables for maximal
health benefits.
Epidemiological studies have shown that
low
vitamin D status is correlated to
increased cancer risk. However, the results of such studies need to
be treated with caution, as they cannot show whether a correlation
between two factors means that one causes the other (
i.e.
correlation does
not imply causation). The possibility that Vitamin D might
protect against cancer has been contrasted with the risk of
malignancy from sun exposure. Since exposure to the sun enhances
natural human production of vitamin D, some cancer researchers have
argued that the potential deleterious malignant effects of sun
exposure are far outweighed by the cancer-preventing effects of
extra vitamin D synthesis in sun-exposed skin. In 2002, Dr. William
B. Grant claimed that 23,800 premature cancer deaths occur in the
US annually due to insufficient UVB exposure (apparently via
vitamin D deficiency). This is higher than 8,800 deaths occurred
from melanoma or squamous cell carcinoma, so the overall effect of
sun exposure might be beneficial. Another research group estimates
that 50,000–63,000 individuals in the United States and 19,000 -
25,000 in the UK die prematurely from cancer annually due to
insufficient vitamin D.
The case of
beta-carotene provides an
example of the importance 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
clinical 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 not significantly,
increased by beta-carotene, leading to an early
termination of the study.
Results reported in the
Journal of the
American Medical Association (JAMA) in 2007 indicate that folic
acid supplementation is not effective in preventing colon cancer,
and folate consumers may be more likely to form colon polyps.
Chemoprevention
The concept that medications could be used to prevent cancer is an
attractive one, and many high-quality clinical trials support the
use of such chemoprevention in defined circumstances.
Daily use of
tamoxifen, a
selective estrogen
receptor modulator (SERM), typically for 5 years, has been
demonstrated to reduce the risk of developing
breast cancer in high-risk women by about 50%.
A recent study reported that the
selective estrogen
receptor modulator raloxifene has
similar benefits to
tamoxifen in
preventing breast cancer in high-risk women, with a more favorable
side effect profile.
Raloxifene is a SERM like
tamoxifen; it has been shown (in the STAR trial)
to reduce the risk of breast cancer in high-risk women equally as
well as tamoxifen. In this trial, which studied almost 20,000
women,
raloxifene had fewer side effects
than
tamoxifen, though it did permit more
DCIS to form.
Finasteride, a
5-alpha-reductase inhibitor, has
been shown to lower the risk of prostate cancer, though it seems to
mostly prevent low-grade tumors.The effect of
COX-2 inhibitors such as
rofecoxib and
celecoxib
upon the risk of colon polyps have been studied in
familial adenomatous
polyposis patientsand in the general population.In both groups,
there were significant reductions in
colon
polyp incidence, but
this came at the price of increased cardiovascular toxicity.
Genetic testing
Genetic testing for high-risk
individuals is already available for certain cancer-related genetic
mutations. Carriers of genetic mutations that increase risk for
cancer incidence can undergo enhanced surveillance,
chemoprevention, or risk-reducing surgery. Early identification of
inherited genetic risk for cancer, along with cancer-preventing
interventions such as surgery or enhanced surveillance, can be
lifesaving for high-risk individuals.
Gene |
Cancer types |
Availability |
BRCA1, BRCA2 |
Breast, ovarian, pancreatic |
Commercially available for clinical specimens |
MLH1, MSH2, MSH6, PMS1, PMS2 |
Colon, uterine, small bowel, stomach, urinary tract |
Commercially available for clinical specimens |
Vaccination
Prophylactic
vaccines have been developed to
prevent infection by oncogenic infectious agents such as viruses,
and therapeutic vaccines are in development to stimulate an immune
response against cancer-specific
epitopes.
As reported above, a preventive
human papillomavirus vaccine
exists that targets certain sexually transmitted strains of
human papillomavirus that are
associated with the development of
cervical cancer and
genital warts. The only two HPV vaccines on
the market as of October 2007 are
Gardasil
and
Cervarix. There is also a
hepatitis B vaccine, which prevents
infection with the hepatitis B virus, an infectious agent that can
cause liver cancer. A canine melanoma vaccine has also been
developed.
Screening
Cancer
screening is an attempt
to detect unsuspected cancers in an asymptomatic population.
Screening tests suitable for large numbers of healthy people must
be relatively affordable, safe, noninvasive 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 in specific
cases. Early diagnosis may lead to extended life, but may also
falsely prolong the lead time to death through
lead time bias or
length time bias.
A number of different screening tests have been developed for
different malignancies.
Breast cancer screening can be done by
breast self-examination,
though this approach was discredited by a 2005 study in over
300,000 Chinese
women. Screening for breast cancer with
mammograms has been shown to reduce the
average stage of diagnosis of breast cancer in a population. Stage
of diagnosis in a country has been shown to decrease within ten
years of introduction of mammographic screening programs.
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 pre-malignant 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 using a
digital rectal exam along with
prostate specific antigen (PSA)
blood testing, though some authorities (such as the
US Preventive Services Task
Force) recommend against routinely screening all men.
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 overdiagnosis, 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, being largely
caused by a virus, it has clear risk factors (sexual contact), and
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. Moreover, 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. Recent studies of
CT
scan-based screening for
lung cancer
in smokers have had equivocal results, and systematic screening is
not recommended as of July 2007.
Randomized clinical trials of
plain-film
chest X-rays to screen for
lung cancer in smokers have shown no benefit for this
approach.
Canine cancer detection has
shown promise, but is still in the early stages of research.
Diagnosis
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 the opinion of a
pathologist, a type of
physician (medical doctor) who specializes in the diagnosis of
cancer and other diseases.
Investigation
People with suspected cancer are investigated with
medical tests. These commonly include
blood tests,
X-rays,
CT scans and
endoscopy.
Biopsy
A cancer may be suspected for a variety of reasons, but the
definitive diagnosis of most malignancies must be confirmed by
histological examination of the cancerous
cells by a
pathologist. Tissue
can be obtained from a
biopsy or
surgery. Many biopsies (such as those of the skin,
breast or liver) can be done in a doctor's office. Biopsies of
other organs are performed under
anesthesia and require
surgery in an
operating
room.
The tissue
diagnosis given by the
pathologist indicates the type of cell that is proliferating, its
histological grade, genetic
abnormalities, and other features of the tumor. Together, this
information is useful to evaluate the
prognosis of the patient and to choose the best
treatment.
Cytogenetics and
immunohistochemistry are other types of
testing that the pathologist may perform on the tissue specimen.
These tests may provide information about the molecular changes
(such as
mutations,
fusion genes, and numerical
chromosome changes) that has happened in the
cancer cells, and may thus also indicate the future behavior of the
cancer (prognosis) and best treatment.
Management
Cancer can be treated by
surgery,
chemotherapy,
radiation therapy,
immunotherapy,
monoclonal antibody therapy 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.
Angiogenesis inhibitors were once
thought to have potential as a "
silver
bullet" treatment applicable to many types of cancer, but this
has not been the case in practice.
Prognosis
Cancer has a reputation for being a deadly disease. While this
certainly applies to certain particular types, the truths behind
the historical connotations of cancer are increasingly being
overturned by advances in medical care. Some types of cancer have a
prognosis that is substantially better than nonmalignant 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.
Emotional impact
Many local organizations offer a variety of practical and support
services to people with cancer. Support can take the form of
support groups,
counseling, advice, financial assistance,
transportation to and from treatment, films or information about
cancer. Neighborhood organizations, local health care providers, or
area hospitals may have resources or services available.
Counseling can provide emotional support to cancer patients and
help them better understand their illness. Different types of
counseling include individual, group, family, peer counseling,
bereavement, patient-to-patient, and sexuality.
Many governmental and charitable organizations have been
established to help patients cope with cancer. These organizations
are often involved in cancer prevention, cancer treatment, and
cancer research.
Epidemiology
[[Image:Malignant neoplasms world map - Death -
WHO2004.svg|thumb|Death rate from malignant cancer per
100,000 inhabitants in 2004.
]]Cancer is responsible for about 25% of all deaths in the U.S.,
and is a major
public health problem
in many parts of the world. In the U.S.,
lung cancer causes about 30% of cancer deaths
but only about 15% of new cancer cases; the most commonly occurring
cancer in men is
prostate cancer
(about 25% of new cases) and in women is
breast cancer (also about 25%). Cancer can
also occur in young children and adolescents, but it is rare (about
150 cases per million in the U.S.), with
leukemia being the most common. In the first year
of life the
incidence is
about 230 cases per million in the U.S., with the most common being
neuroblastoma.
Over a third of cancer deaths worldwide are due to potentially
modifiable risk factors, which are headed by
tobacco smoking,
alcohol use, and diets low in
fruit and
vegetables. In
developed countries
overweight and
obesity is also a leading cause of cancer,
and in low-and-middle-income countries sexual transmission of
human papillomavirus is a
leading risk factor for
cervical
cancer.
In the developed world, one in three people will develop cancer
during their lifetimes. If all cancer patients survived and cancer
occurred randomly, the lifetime odds of developing an second
primary cancer would be one in nine. However, cancer survivors have
an increased risk of developing a second primary cancer, and the
odds are about two in nine. About half of these second primaries
can be attributed to the normal one-in-nine risk associated with
random chance. The increased risk is believed to be primarily due
to the same risk factors that produced the first cancer, such as
the person's genetic profile, alcohol and tobacco use, obesity, and
environmental exposures, and partly due, in some cases, to the
treatment for the first cancer, which might have included mutagenic
chemotherapeutic drugs or radiation. Cancer survivors may also be
more likely to comply with recommended screening, and thus may be
more likely than average to detect cancers.
History
Today, the Greek term
carcinoma is the
medical term for a malignant tumor derived from
epithelial cells. It is
Celsus who translated
carcinos into the
Latin
cancer, also meaning crab.
Galen used
"
oncos" to describe
all tumours, the root for the
modern word
oncology.
Hippocrates described several kinds of
cancers. He called benign tumours
oncos,
Greek for swelling, and malignant tumours
carcinos, Greek for
crab or
crayfish. This name comes from the appearance of
the cut surface of a solid malignant tumour, with "the veins
stretched on all sides as the animal the crab has its feet, whence
it derives its name" (see picture). He later added the suffix
-oma, Greek for swelling, giving the name
carcinoma. Since it was against Greek tradition to open
the body, Hippocrates only described and made drawings of outwardly
visible tumors on the skin, nose, and breasts. Treatment was based
on the
humor theory of four bodily fluids
(black and yellow bile, blood, and phlegm). According to the
patient's humor, treatment consisted of diet, blood-letting, and/or
laxatives. Through the centuries it was discovered that cancer
could occur anywhere in the body, but humor-theory based treatment
remained popular until the 19th century with the discovery of
cells.
The oldest
known description and surgical treatment of
cancer was discovered in Egypt
and dates
back to approximately 1600 B.C. The
Papyrus describes 8 cases of ulcers of the breast
that were treated by cauterization, with a tool called "the fire
drill." The writing says about the disease, "There is no
treatment."
Another very early
surgical treatment for
cancer was described in the 1020s by
Avicenna (Ibn Sina) in
The Canon of Medicine. He stated
that the
excision should be radical and
that all diseased
tissue should be
removed, which included the use of
amputation or the removal of
veins running in the direction of the
tumor. He also recommended the use of
cauterization for the area being treated if
necessary.
In the 16th and 17th centuries, it became more acceptable for
doctors to
dissect bodies to discover the
cause of death. The German professor
Wilhelm Fabry believed that breast cancer was
caused by a milk clot in a mammary duct. The Dutch professor
Francois de la Boe
Sylvius, a follower of
Descartes,
believed that all disease was the outcome of chemical processes,
and that acidic
lymph fluid was the cause of
cancer. His contemporary
Nicolaes Tulp
believed that cancer was a poison that slowly spreads, and
concluded that it was
contagious.
The first cause of cancer was identified by British surgeon
Percivall Pott, who discovered in
1775 that cancer of the
scrotum was a common
disease among
chimney sweeps. The work
of other individual physicians led to various insights, but when
physicians started working together they could make firmer
conclusions.
With the widespread use of the microscope in the 18th century, it
was discovered that the 'cancer poison' spread from the primary
tumor through the lymph nodes to other sites ("
metastasis"). This view of the disease was first
formulated by the English surgeon
Campbell De Morgan between 1871 and 1874.
The use of
surgery to treat cancer had poor
results due to problems with hygiene. The renowned Scottish surgeon
Alexander Monro saw only 2 breast
tumor patients out of 60 surviving surgery for two years. In the
19th century,
asepsis improved surgical
hygiene and as the
survival
statistics went up, surgical removal of the tumor became the
primary treatment for cancer. With the exception of
William Coley who in the late 1800s felt that
the rate of cure after surgery had been higher
before
asepsis (and who injected bacteria into tumors with mixed results),
cancer treatment became dependent on the individual art of the
surgeon at removing a tumor. During the same period, the idea that
the body was made up of various
tissues, that in turn were made up of
millions of cells, laid rest the humor-theories about chemical
imbalances in the body. The age of
cellular pathology was born.
When
Marie Curie and
Pierre Curie discovered
radiation at the end of the 19th century, they
stumbled upon the first effective non-surgical cancer treatment.
With radiation also came the first signs of multi-disciplinary
approaches to cancer treatment. The surgeon was no longer operating
in isolation, but worked together with hospital radiologists to
help patients. The complications in communication this brought,
along with the necessity of the patient's treatment in a hospital
facility rather than at home, also created a parallel process of
compiling patient data into hospital files, which in turn led to
the first statistical patient studies.
A founding paper of cancer epidemiology was the work of
Janet Lane-Claypon, who published a
comparative study in 1926 of 500 breast cancer cases and 500
control patients of the same background and lifestyle for the
British Ministry of Health. Her ground-breaking work on cancer
epidemiology was carried on by
Richard
Doll and
Austin Bradford
Hill, who published "
Lung Cancer and
Other Causes of Death In Relation to
Smoking. A Second Report on the Mortality of British
Doctors" followed in 1956 (otherwise known as the
British doctors study).
Richard Doll left the
London
Medical Research Center (MRC), to start the
Oxford
unit for Cancer epidemiology in 1968. With
the use of
computers, the unit was the
first to compile large amounts of cancer data. Modern
epidemiological methods are closely linked to current concepts of
disease and
public health policy. Over
the past 50 years, great efforts have been spent on gathering
data across medical practise, hospital, provincial, state, and even
country boundaries, as a way to study the interdependence of
environmental and cultural factors on cancer incidence.
Cancer patient treatment and studies were restricted to individual
physicians' practices until
World War
II, when medical research centers discovered that there were
large international differences in disease incidence. This insight
drove national public health bodies to make it possible to compile
health data across practises and hospitals, a process that many
countries do today. The Japanese medical community observed that
the bone marrow of victims of the
atomic bombings of
Hiroshima and Nagasaki was completely destroyed. They concluded
that diseased
bone marrow could also be
destroyed with radiation, and this led to the discovery of bone
marrow transplants for
leukemia. Since
World War II, trends in cancer treatment are to improve on a
micro-level the existing treatment methods, standardize them, and
globalize them as a way to find cures through
epidemiology and international
partnerships.
Research directions
Cancer research is the intense scientific effort to understand
disease processes and discover possible therapies. The improved
understanding of
molecular biology
and
cellular biology due to cancer
research has led to a number of new, effective treatments for
cancer since President Nixon declared "
War
on Cancer" in 1971.
Since 1971 the United States
has invested over $200 billion on cancer research;
that total includes money invested by public and private sectors
and foundations. Despite this substantial investment, the
country has seen a five percent decrease in the cancer death rate
(adjusting for size and age of the population) between 1950 and
2005.
Leading cancer research organizations and projects include the
American
Association for Cancer Research, the
American Cancer Society (ACS), the
American Society
of Clinical Oncology, the
European
Organisation for Research and Treatment of Cancer, the
National Cancer Institute, the
National
Comprehensive Cancer Network, and
The Cancer Genome Atlas project at
the NCI.
References
General references
- Pazdur R, Wagman LD, Camphausen KA, Hoskins WJ, Eds.
Cancer Management: A Multidisciplinary
Approach. 11th ed. 2009.
- The Basic Science of Oncology 4th ed. Tannock IF, Hill
RP et al. (eds.) (2005). McGraw-Hill. ISBN
0-07138-774-9.
- Principles of Cancer Biology. Kleinsmith, LJ (2006).
Pearson Benjamin Cummings. ISBN 0-80534-003-3.
- Food, Nutrition, Physical Activity, and the Prevention of
Cancer: a Global Perspective. World Cancer Research Fund
(2007). ISBN 978-0-9722522-2-5. Full text
- Cancer Medicine, 6th Edition—Textbook
- Encyclopedia of Cancer—4 volume reference
work
External links