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Cancer

2007 Schools Wikipedia Selection. Related subjects: Health and medicine

   CAPTION: Cancer
   Classifications and external resources

   When normal cells are damaged beyond repair, they are eliminated by
   apoptosis. Cancer cells avoid apoptosis and continue to multiply in an
   unregulated manner
   DiseasesDB 28843
   MedlinePlus 001289
   MeSH C04

   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 principal 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,
   and may be passed down from one generation to the next as a result of
   mutations within germ lines.

   Many forms of cancer are associated with exposure to environmental
   factors such as tobacco smoke, radiation, alcohol, and certain viruses.
   While some of these risk factors can be avoided or reduced, there is no
   known way to entirely avoid the disease.

History

   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.
   Breast cancer in a mastectomy specimen (top). The cancerous tumour
   (pale yellow) resembles the figure of a crab (bottom photo, by Chouby,
   Flickr), giving the disease its name.
   Enlarge
   Breast cancer in a mastectomy specimen (top). The cancerous tumour
   (pale yellow) resembles the figure of a crab (bottom photo, by Chouby,
   Flickr), giving the disease its name.

   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 probably comes from the
   appearance of the cut surface of a solid malignant tumour, with a
   roundish hard centre surrounded by pointy projections, vaguely
   resembling the shape of a crab (see photo). 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 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 came also 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.

   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 bomb victims in 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 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.

Nomenclature and classification

   The following closely related terms may be used to designate abnormal
   growths:
     * Neoplasia and neoplasm are the scientific designations for
       cancerous diseases. This group contains a large number of different
       diseases. Neoplasms can be benign or malignant.
     * Cancer is a widely used word that is usually understood as
       synonymous with malignant neoplasm. It is occasionally 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
     * Germinoma: tumors derived from germ cells, normally found in the
       testicle and ovary
     * Choriocarcinoma: malignant tumors derived from the placenta

   Malignant 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.
   Male • most common Male • cause of death Female • most common Female •
   cause of death
   prostate cancer (33%) lung cancer (31%) breast cancer (32%) lung cancer
   (27%)
   lung cancer (13%) prostate cancer (10%) lung cancer (12%) breast cancer
   (15%)
   colorectal cancer (10%) colorectal cancer (10%) colorectal cancer (11%)
   colorectal cancer (10%)
   bladder cancer (7%) pancreatic cancer (5%) endometrial cancer (6%,
   uterus) ovarian cancer (6%)
   cutaneous melanoma (5%) leukemia (4%) non-Hodgkin's lymphoma (4%)
   pancreatic cancer (6%)

Childhood cancers

   Cancer can also occur in young children and adolescents, but it is
   rare. Some studies have concluded that pediatric cancers, especially
   leukemia, are on an upward trend.

   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.

Causes and pathophysiology

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.
   Enlarge
   Cancers are caused by a series of mutations. Each mutation alters the
   behaviour 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.

   Despite nearly half of all cancers may involve alterations in p53, its
   tumor suppressor function is poorly understood. It is clear it has two
   functions: one a nuclear role as a transcription factor, and the other
   a cytoplasmic role in cell cycle and division regulation and apoptosis.

   The Warburg effect is the preferential use of glycolyisis for energy to
   sustain cancer growth. p53 has been shown to regulate the shift from
   the respiratory to the glycolytic pathway. Synthesis of Cytochrome c
   Oxidase 2 (SCO2) has been recognized as the downstream mediator of this
   effect. SCO2 is critical for regulating the cytochrome c oxidase
   complex within the mitochondria, and p53 can disrupt the SCO2 gene. P53
   regulation of SCO2 and mitochondrial respiration may provide a possible
   explanation for the Warburg effect

   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. Knudson’s two hit model has recently been challenged by
   several investigators. Inactivation of one allele of some tumor
   suppressor genes is sufficient to cause tumors. This phenomenon is
   called haploinsufficiency and has been demonstrated by a number of
   experimental approaches. Tumors caused by haploinsufficiency usually
   have a later age of onset when compared with those by a two hit
   process.

   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 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 virus, Epstein-Barr virus, and human T-lymphotropic virus.
   Experimental and epidemiologic 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 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.
   Enlarge
   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 behaviour, 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.
   Enlarge
   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, alcohol, tanning choices, and certain sexually transmitted
   diseases are the major risks. "Most cancers are related to known
   lifestyle factors."

   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.

Epidemiology

   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 Centre (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 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.

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).

   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 ), 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
   sexually transmitted diseases, the use of exogenous hormones, exposure
   to ionizing radiation and ultraviolet radiation, certain occupational
   and chemical exposures, and infectious agents.

   See Alcohol and cancer for more on that topic.

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.

   However, Randomized Clinical Trials (RCTs) also have drawbacks in
   cancer prevention, particularly in micronutrient deficiencies, which
   are thought by some to be a major contributor to cancer. RCTs involve
   huge numbers of people, take many years to complete, and are therefore
   extremely expensive and complicated, and therefore few are done. In
   addition, these randomized clinical trials usually test only a single
   dose. An alternative, which is likely to be more useful, is to do
   shorter intervention trials focusing on other endpoints related to
   cancer, such as DNA damage. These trials can test a variety of doses on
   fewer people to determine what level of micronutrient intake (or,
   better, micronutrient concentration in blood) keeps DNA damage to a
   minimum.

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.

Diagnosing cancer

   Most cancers are initially recognized either because signs or symptoms
   appear or through screening. Neither of these lead to a definitive
   diagnosis, which usually requires 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), anaemia 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 behaviour 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.

Treatment of cancer

   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.

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 body's 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.

Monoclonal antibody therapy

   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.

Immunotherapy

   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.
   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.

   Chronic pain due to cancer is almost always associated with continuing
   tissue damage due to the disease process or the treatment (i.e.
   surgery, radiation, chemotherapy). Although there is always a role for
   environmental factors and affective disturbances in the genesis of pain
   behaviors, these are not usually the predominant etiologic factors in
   patients with cancer pain. Furthermore, many patients with severe pain
   associated with cancer are nearing the end of their lives and
   palliative therapies are required. Issues such as social stigma of
   using opioids, work and functional status, and health care consumption
   are not likely to be important in the overall case management. Hence,
   the typical strategy for cancer pain management is to get the patient
   as comfortable as possible using opioids and other medications,
   surgery, and physical measures.

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", "cabbage diet" or
   megavitamin therapy), electromagnetic therapy with electrical devices
   (e.g., "rhumart", "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. The Ralph Moss Reports are a source of information on
   CAM and conventional cancer treatments from a biologically based,
   alternative medicine point of view with detailed reports on a variety
   of cancer types.

Coping with cancer

   Many local organizations offer a variety of practical and support
   services to people with cancer. Support can take the form of support
   groups, counseling, advice, financial assistance, transportation to and
   from treatment, films or information about cancer. Neighbourhood
   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, Cancer Research Foundation, Canadian Cancer Society,
   International Agency for Research on Cancer, The Cancer Council
   Australia and the National Cancer Institute (US).

Social impact

   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

   Cancer research is the intense scientific effort to understand disease
   processes and discover possible therapies. Although understanding of
   cancer has greatly increased since the last decades of the 20th
   century, few radically new therapies have been discovered.

   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.

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