Cancer
|
When normal cells are damaged beyond repair, they are eliminated by apoptosis. Cancer cells avoid apoptosis and continue to multiply in an unregulated manner. |
Cancer is a class of
diseases or disorders characterized by uncontrolled
division of
cells and the ability of these cells to invade other
tissues, either by direct growth into adjacent tissue through
invasion or by implantation into distant sites by
metastasis. Metastasis is defined as the stage in which cancer cells are transported through the
bloodstream or
lymphatic system. Cancer may affect people at all ages, but risk tends to increase with age, due to the fact that
DNA damage becomes more apparent in
aging DNA. It is one of the leading causes of death in
developed countries.
There are many types of cancer. Severity of symptoms depends on the site and character of the malignancy and whether there is metastasis. A definitive diagnosis usually requires the
histologic examination of tissue by a
pathologist. This tissue is obtained by
biopsy or
surgery. 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 the type of cancer pathology. Drugs that target specific cancers already exist for several cancers. If untreated, cancers may eventually cause illness and
death, though this is not always the case.
The unregulated growth that characterizes cancer is caused by damage to
DNA, resulting in
mutations to
genes that encode for
proteins controlling cell division. Many mutation events may be required to transform a normal cell into a malignant cell. These mutations can be caused by chemicals or physical agents called
carcinogens, by close exposure to radioactive materials, or by certain viruses that can insert their DNA into the human genome. Mutations occur spontaneously, or are passed down generations as a result of germ line mutations.
Many forms of cancer are associated with exposure to
environmental factors such as
tobacco smoke,
radiation,
alcohol and certain
viruses. While some of these can be avoided, there is no known way of certain avoidance of the disease.
Today,
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.
[Ralph W. Moss, Ph.D Galen on Cancer - How Ancient Physicians Viewed Malignant Disease 1989 Speech]Hippocrates described several kinds of cancers. He called benign tumours
oncos,
Greek for swelling, and malignant tumours
carcinos, Greek for
crab or
crayfish. This strange choice of name probably comes from the appearance of the cut surface of a solid malignant tumour, with a roundish hard center surrounded by pointy projections, vaguely resembling the silhouette of a crab. 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.
Though treatment remained the same, 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.
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"). The use of
surgery to treat cancer had poor results due to problems with hygiene. The renowned Scottish surgeon
Alexander Monro (1697-1767) 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 1800's 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 came also the first signs of multi-disciplinary approaches to cancer treatment. The surgeon was no longer operating as an island, 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.
Cancer patient treatment and studies were restricted to individual physician's practises until
WWII, 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
Hiroshima and
Nagasaki victims 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 WWII, 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.
The following closely related terms may be used to designate abnormal growths:
Neoplasia and
neoplasm are the accurate, scientific names for this group of diseases as defined in the first paragraph above. This group contains a large number of different diseases; the usual classification is listed below. Neoplasms can be
benign or
malignant.
Cancer is a widely used word that is usually understood as synonymous with
malignant neoplasm. Occasionally, it is used instead of
carcinoma, a sub-group of malignant neoplasms. Because of its overwhelming popularity relative to 'neoplasia', it is used frequently instead of 'neoplasia', even by scientists and physicians, especially when discussing neoplastic diseases as a group.
Tumor in medical language simply means swelling or lump, either neoplastic, inflammatory or other. In common language, however, it is synonymous with 'neoplasm', either benign or malignant. This is inaccurate since some neoplasms usually do not form tumors, for example
leukemia or
carcinoma in situ.
Cancers are classified by the type of cell that resembles the tumor and, therefore, the tissue presumed to be the origin of the tumor. The following general categories are usually accepted:
*
Carcinoma: malignant tumors derived from
epithelial cells. This group represent the most common cancers, including the common forms of
breast,
prostate,
lung and
colon cancer.
*
Lymphoma and
Leukemia: malignant tumors derived from
blood and
bone marrow cells
*
Sarcoma: malignant tumors derived from
connective tissue, or
mesenchymal cells
*
Mesothelioma: tumors derived from the
mesothelial cells lining the
peritoneum and the
pleura.
*
Glioma: tumors derived from glia, the most common type of
brain cell
*
germ cell tumours: tumors derived from germ cells, normally found in the
testicle and
ovary*
Choriocarcinoma: malignant tumors derived from the
placentaMalignant tumors are usually named using the Latin or Greek root of the organ as a prefix and the above category name as the suffix. For instance, a malignant tumor of liver cells is called
hepatocarcinoma; a malignant tumor 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 are named using
-oma as a suffix. For instance, a benign tumor of the smooth muscle of the uterus is called
leiomyoma (the common name of this frequent tumor is
fibroid). This nomenclature is however somewhat inconsistent, since several "malignant" tumor growths also have this suffix in their names, e.g. neuroblastoma, lymphoma and melanoma.
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.
The statistics below are for adults in the United States. These statistics vary substantially in other countries.
Childhood cancers
Cancer can also occur in young children and adolescents, but it is rare. Pediatric cancers, especially leukemia, are on an upward trend. Though some studies have not shown this, others done over a longer scale of time have so indicated.
The age of peak incidence of cancer in children occurs during the first year of life.
Leukemia (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 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.
Origins of cancer
Cell division or cell proliferation is a physiological process that occurs in almost all tissues and under many circumstances. Normally the balance between proliferation and programmed 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, which means the initiation or generation 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. In order for cells to start dividing uncontrollably, genes which regulate cell growth must be damaged.
Proto-oncogenes are genes which promote cell growth and
mitosis, a process of cell division, and
tumor suppressor genes discourage cell growth, or temporarily halt cell division in order to carry out
DNA repair. Typically, a series of several
mutations to these genes are required before a normal cell transforms into a cancer cell.
Proto-oncogenes promote cell growth through a variety of ways. Many can produce
hormones, a "chemical messenger" between cells which encourage mitosis, the effect of which depends on the
signal transduction of the receiving tissue or cells. Some are responsible for the signal transduction system and signal
receptors in cells and tissues themselves, thus controlling the sensitivity to such hormones. They often produce
mitogens, or are involved in
transcription of DNA in
protein synthesis, which creates the
proteins and
enzymes responsible for producing the products and
biochemicals cells use and interact with.
Mutations in proto-oncogenes can modify their
expression and function, increasing the amount or activity of the product protein. When this happens, they become
oncogenes, and thus cells have a higher chance to divide excessively and uncontrollably. The chance of cancer cannot be reduced by removing proto-oncogenes from the
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 anti-proliferation signals and proteins that suppress mitosis and cell growth. Generally tumor suppressors are
transcription factors that are activated by cellular
stress or DNA damage. Often DNA damage will cause the presence of free-floating genetic material as well as other signs, and will trigger enzymes and pathways which lead to the activation of tumor suppressor genes. The functions of such genes is to arrest the progression of cell cycle in order to carry out DNA repair, preventing mutations from being passed on to daughter cells. Canonical tumor suppressors include the
p53 protein, which is a transcription factor activated by many cellular stressors including
hypoxia and
ultraviolet radiation damage.
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 and tumor suppressor genes, which was first
hypothesised as the
Knudson hypothesis. 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. Often, because these genes regulate the processes that prevent most damage to genes themselves, the rate of mutations increase as one gets older, because DNA damage forms a
feedback loop.
Usually, oncogenes are
dominant, as they contain
gain-of-function mutations, while mutated tumor suppressors are
recessive, as they contain
loss-of-function mutations. Each cell has two copies of the same gene, one from each parent, and under most cases gain of function mutation in one copy of a particular proto-oncogene is enough to make that gene a true oncogene, while usually loss of function mutation needs to happen in both copies of a tumor suppressor gene to render that gene completely non-functional. However, cases exist in which one loss of function copy of a tumor suppressor gene can render the other copy non-functional. This phenomenon is called the
dominant negative effect and is observed in many p53 mutations.
Mutation of tumor suppressor genes that are passed on to the next generation of not merely cells, but their
offspring can cause increased likelihoods for cancers to be inherited. Members within these families have increased incidence and decreased latency of multiple tumors. The mode of inheritance of mutant tumor suppressors is that affected member inherits a defective copy from one parent, and a normal copy from another. Because mutations in tumor suppressors act in a recessive manner (although there are exceptions), the loss of the normal copy creates the cancer
phenotype. For instance, individuals who are
heterozygous for
p53 mutations are often victims of
Li-Fraumeni syndrome, and those who are heterozygous for
Rb mutations develop
retinoblastoma. Similarly, mutations in the
APC gene are linked to
adenopolyposis colon cancer, with thousands of polyps in colon while young, while mutations in
BRCA1 and
BRCA2 lead to early onset of
breast cancer.
Cancer pathology is ultimately due to the accumulation of DNA mutations that negatively effect expression of tumour suppressor proteins or positivly effect the expression of proteins that drive the cell cycle. Substances that cause these 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
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
estrogen. These are thought to promote cancers through their stimulating effect on the rate of cell
mitosis. Faster rates of mitosis increasingly leave less opportunities for repair enzymes to repair damaged DNA during
DNA replication, increasing 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.
Furthermore, many cancers originate from a
viral infection; this is especially true in animals such as
birds, but less so in
humans, as viruses are only responsible for 15% of human cancers. The mode of virally-induced tumors can be divided into two,
acutely-transforming or
slowly-transforming. In acutely transforming viruses, the viral particles carry a gene that encodes for 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 inserted, especially as viral genome insertion is an obligatory part of
retroviruses, near a proto-oncogene in the host genome. The viral
promoter or other transcription regulation elements in turn cause overexpression of that proto-oncogene, which in turn induces uncontrolled cellular proliferation. Because viral genome insertion is not specific to proto-oncogenes and the chance of insertion near that proto-oncogene is low, slowly-transforming viruses have very long tumor latency compared to acutely-transforming viruses, which already carry the viral-oncogene.
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, some tumors have a defective p53 gene. This mutation is associated with poor prognosis, since those tumor cells are less likely to go into
apoptosis or
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) due to overabundance of
telomerase* 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 regulation. Cells that divide at a high rate, such as
epithelials, 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 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 recognised
syndromes of cancer with a hereditary component, often a defective tumor suppressor
allele. 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
Lifestyle factors
 |
The incidence of lung cancer is highly correlated with smoking. Source:NIH. |
The most consistent finding, over decades of research, is the strong association between
tobacco use and cancers of many sites. Hundreds of epidemiological studies have confirmed this association. Further support comes from the fact that
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. Lifestyle choices cause cancer: tobacco, diet, exercise, sex, alcohol, and tanning choices are the major risks. "Most cancers are related to known lifestyle factors."
[Update: Is There a Cancer Epidemic in the United States? American Council on Science and Health, 1995.]There is also a growing body of research that correlates cancer incidence with the lower levels of
melatonin produced in the body when people spend more time in bright-light conditions, as happens typically in the well-lit nighttime environments of the more developed countries. This effect is compounded in people who sleep fewer hours and in people who work at night, two groups that are known to have higher cancer rates.
Cancer
epidemiology is the study of the incidence of cancer as a way to infer possible trends and causes. The first such 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.
A founding paper of this discipline 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," in
1956), (otherwise known as the
British doctors study). Richard Droll 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.
The biggest problem facing cancer epidemiology today is the changing concept of 'cancer
incidence'. For example, a
breast cancer tumor with a very slow growth rate may be found with a
mammogram at 50 years, while the same tumor may have been found as a noteworthy 'lump' at 70 years, depending on the specific growth factors affecting that particular patient's case. As
diagnostic tools improve, this has a direct impact on the epidemiological data.
In some Western countries, such as the USA
and the UK
[Cancer: Number one killer (9 November, 2000). BBC News online. Retrieved 2005-01-29.], 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 epidemiologic transition 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 neighboring 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.
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).
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), smoking (although 20% of women with lung cancer have never smoked, versus 10% of men [
1]), 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 not significantly, increased by beta-carotene, leading to an early termination of the study.
[National Cancer Institute Questions and Answers About Beta Carotene Chemoprevention Trials U.S. National Institutes of Health]Other chemoprevention agents
Daily use of
tamoxifen, a selective
estrogen receptor modulator, typically for 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).
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.
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.
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 often 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
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 indicates the type of cell that is proliferating, its histological
grade and other features of the tumor. Together, this information is useful to evaluate the
prognosis of this patient and choose the best
treatment.
Cytogenetics and
immunohistochemistry may provide information about future behavior of the cancer (prognosis) and best treatment.
Screening
Cancer
screening is an attempt to detect unsuspected cancers in the 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. 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 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 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
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 a cancer, 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.
Canine cancer detection has shown promise, but is still in the early stages of research.
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
In theory, cancers can be cured if entirely removed by
surgery, but this is not always possible. When the cancer has
metastasized to other sites in the body prior to surgery, complete surgical excision is usually impossible.
Examples of surgical procedures for cancer 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. A single cancer cell is invisible to the naked eye but can regrow into a new tumor, a process called
recurrence. For this reason, the
pathologist will examine the surgical specimen to determine if a margin of healthy tissue is present, thus decreasing the chance that microscopic cancer cells are left in the patient.
In addition to removal of the primary tumor, surgery is often necessary for
staging, e.g. determining the extent of the disease and whether it has
metastasized to regional
lymph nodes. Staging is a major determinant of
prognosis and of 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.
The treatment of some
Leukaemias and
Lymphomas requires the use of high-dose chemotherapy, and
Total Body Irradiation. This treatment ablates the bone marrow, and hence the bodies' ability to recover and repopulate the blood. For this reason, bone marrow, or peripheral blood stem cell harvesting is carried out before the ablative part of the therapy, to enable "rescue" after the treatment has been given. This is known as autologous transplantation. Alternatively, bone marrow may be transplanted from a Matched Unrelated Donor.
Immunotherapy
Immunotherapy is the use of
immune mechanisms against tumors. These are used in various forms of cancer, such as
breast cancer (
trastuzumab/Herceptin®) and
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.
Other, more contemporary methods for generating non-specific immune response against tumours include intravesical
BCG immunotherapy for superficial bladder cancer, and use of
interferon and
interleukin.
Vaccines to generate non-specific
immune responses are the subject of intensive research for a number of tumours, notably
malignant melanoma and
renal cell carcinoma.
Radiation therapy
Radiation therapy (also called radiotherapy, X-ray therapy, or irradiation) is the use of ionizing radiation to kill cancer cells and shrink tumors. Radiation therapy can be administered externally via
external beam radiotherapy (EBRT) or internally via
brachytherapy. The effects of radiation therapy are localised and confined to the region being treated. 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. In addition, they cut off the blood supply to the cancer cells causing them to die in a process called
necrosis. 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. Hence, it is given in many fractions, allowing healthy tissue to recover between fractions.
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, stomach, uterus, or soft tissue sarcomas. Radiation is also used to treat leukemia and lymphoma. Radiation dose to each site depends on a number of factors, including the radiosensitivity of each cancer type and whether there are tissues and organs nearby that may be damaged by radiation. Thus, as with every form of treatment, radiation therapy is not without its side effects.
Hormonal suppression
The growth of some cancers can be inhibited by providing or blocking certain hormones. Common examples of hormone-sensitive tumors include certain types of breast and prostate cancers. Removing or blocking
estrogen or
testosterone is often an important additional treatment.
Symptom control
Although the control of the symptoms of cancer is not typically thought of as a treatment directed at the cancer, it is an important determinant of the
quality of life of cancer patients, and plays an important role in the decision whether the patient is able to undergo other treatments. Although all practicing doctors have the therapeutic skills to control pain, nausea, vomiting, diarrhea, hemorrhage and other common problems in cancer patients, the multidisciplinary specialty of
palliative care has arisen specifically in response to the symptom control needs of this group of patients.
Pain medication, such as
morphine and
oxycodone, and
antiemetics, drugs to suppress nausea and vomiting, are very commonly used in patients with cancer-related symptoms.
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.
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.
As of
October 2005, researchers found that an experimental vaccine for
HPV types 16 and 18 was 100% successful at preventing infection with these types of HPV and, thus, are able to prevent the majority of cervical cancer cases
.
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. Conventional medical practitioners may describe non-conventional treatment methods as a "complement" to 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.
Some
complementary measures include
prayer or psychological approaches such as "imaging" or
meditation to aid in pain relief, or improve mood. The benefits of these approaches have not been scientifically proven and therefore face skepticism. 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, and
homeopathic remedies), unconventional use of conventional drugs (e.g.,
insulin), purges or
enemas, physical manipulations of the body, various
herbs or herbal preparations such as
essiac. Some of these alternative treatments may be ineffective or dangerous. Using these modalities as sole treatment for potentially fatal conditions such as cancer are generally not recommended by the majority of medical professionals.
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.
While some people are reluctant to seek counseling, studies show that having someone to talk to reduces stress and helps people both mentally and physically. Counseling can also provide emotional support to cancer patients and help them better understand their illness. Different types of counseling include individual, group, family, self-help (sometimes called peer counseling), 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,
Lance Armstrong Foundation,
BC Cancer Agency,
Macmillan Cancer Relief , the
Terry Fox Foundation,
Cancer Research UK,
Canadian Cancer Society,
International Agency for Research on Cancer and the
National Cancer Institute (US).
Once referred to as "the C-word," 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.
Cancer research is the intense scientific effort to understand disease processes and discover possible therapies. While understanding of cancer has greatly increased since the last decades of the 20th century, radically new therapies are only discovered and introduced gradually.
Targeted therapy which first became available in the late 1990s has had a significant impact in the treatment of some types of cancer, and is currently a very active research area. This constitutes the use of agents specific for the deregulated proteins of cancer cells. Small molecules (such as the tyrosine kinase inhibitors
imatinib and
gefitinib) and
monoclonal antibodies have proven to be a major step in oncological treatment.
Targeted therapy can also involve small peptidic structures as ´homing device´ which can bind to cell surface receptors or affected
extracellular matrix surrounding the tumor. Radionuclides which are attached to this peptides (e.g. RGDs) eventually kill the cancer cell if the nuclide decays in the vicinity of the cell (vide supra
Radiation therapy). Especially oligo- or multimeris of these binding motifs are of great interest, since this can lead to enhanced tumor specificity and avidity.
*
Oncology*
List of oncology-related termsGeneral references:
*
The Basic Science of Oncology. Tannock IF, Hill RP
et al (eds) 4th ed.2005 McGraw-Hill.
*
Principles of Cancer Biology. Kleinsmith, LJ (2006). Pearson Benjamin Cummings.
*
Full textProfessional and research
*
The World Health Organisation's cancer site A review of worldwide strategies for the prevention and treatment of cancer.
*
National Cancer Institute US Government agency responsible for conducting and supporting research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer, rehabilitation from cancer, and the continuing care of cancer patients and the families of cancer patients.
*
National Comprehensive Cancer Network - Free guidelines for professionals and many pages of quality information for patients with all types of cancers
*
The Institute of Cancer Research One of the world's foremost independent cancer research organisations, based in the United Kingdom.
*
EORTC European Organization for Research and Treatment of Cancer. A European non-profit organization that sets up and executes clinical trials.
*
International Society for Biological Therapy of Cancer Society of medical professionals committed to investigating, developing and utilizing biologicals and biological therapy for the treatment of malignant disease.
*
National Cancer Institute of Canada Longest-standing Canadian research organization devoted to advancing cancer control.
*
Cancer Facts & Figures 2005 - 2005 United States Cancer Statistics
*
Canadian Cancer Statistics 2006 - This publication reports cancer incidence and mortality in Canada, analyzed by gender, age and province/territory.
*
Cancer Medicine, 6th Edition Textbook
*
Diet, Nutrition and the prevention of chronic diseases (including cancer) by a Joint
WHO/
FAO Expert consultation (2003).
Summary by
GreenFacts.
Support and advocacy
*
American Cancer Society Patient advocate group
*
Canadian Cancer Society Information on all types of cancer, ways to reduce your risk. Support for people living with cancer. Advocating for healthy public policy.
*
American Association for Cancer Research *
The Leukemia and Lymphoma Society*
Cancer from
MedlinePlus - provides links to news, general sites, diagnosis, treatment and alternative therapies, clinical trials, research, related issues, organizations, other MedlinePlus
Cancers Topics and
Living with Cancer, and more. Also, links to pre-formulated searches of the
MEDLINE/PubMed database for recent research articles.
*
Cancer Research UK - Cancer Resources - In-depth, up-to-date information for people with a professional or general interest in cancer and health.
*
Cancer Council of Australia - Australia's national non-government cancer control organisation, involved in research, information, prevention, patient treatment and support.
*
Healing Cancer Naturally: Holistic Cancer Cure zh-yue:癌
