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| Image = Normal cancer cell division from NIH.png | | | Image = Normal cancer cell division from NIH.png | |
| Caption = When normal cells are damaged beyond repair, they are eliminated by [[apoptosis]] (A). Cancer cells avoid apoptosis and continue to multiply in an unregulated manner (B). | | | Caption = When normal cells are damaged beyond repair, they are eliminated by [[apoptosis]] (A). Cancer cells avoid apoptosis and continue to multiply in an unregulated manner (B). | |
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| MedlinePlus = 001289 |
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| {{SK}} Neoplasia, malignant; malignant neoplastic conditions | | {{SK}} Neoplasia, malignant; malignant neoplastic conditions |
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| ==Overview== | | ==[[Cancer overview|Overview]]== |
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| '''Cancer''' is a group of [[disease]]s in which [[cell (biology)|cells]] are ''aggressive'' (grow and [[cell division|divide]] without respect to normal limits), ''invasive'' (invade and destroy adjacent tissues), and sometimes ''[[metastatic]]'' (spread to other locations in the body). These three [[malignant]] properties of cancers differentiate them from [[benign tumor]]s, which are self-limited in their growth and don't invade or metastasize (although some benign tumor types are capable of becoming malignant). Cancer may affect people at all ages, even [[fetus]]es, but risk for the more common varieties tends to increase with age.<ref name="Cancer Research UK">{{cite web | last =Cancer Research UK | first = | authorlink = | coauthors = | title =UK cancer incidence statistics by age | work = | publisher = |date=Jan 2007 | url =http://info.cancerresearchuk.org/cancerstats/incidence/age/ | format = | doi = | accessdate =2007-06-25 }}</ref> Cancer causes about 13% of [[causes of death|all deaths]].<ref name="WHO">{{cite web | last =WHO | first = | authorlink =World Health Organization | coauthors = | title =Cancer | work = | publisher =World Health Organization |date=February 2006 | url =http://www.who.int/mediacentre/factsheets/fs297/en/ | format = | doi = | accessdate =2007-06-25 }}</ref> According to the [[American Cancer Society]], 7.6 million people died from cancer in the world during 2007.<ref name="American Cancer Society">{{cite web | last =American Cancer Society | first = | authorlink =Reuters | coauthors = | title =Report sees 7.6 million global 2007 cancer deaths | work = | publisher =Reuters |date=December 2007 | url =http://today.reuters.com/news/articlenews.aspx?type=healthNews&storyid=2007-12-17T052342Z_01_N16330649_RTRUKOC_0_US-CANCER-WORLD.xml | format = | doi = | accessdate =2007-12-17 }}</ref> Apart from humans, forms of cancer may affect other animals and plants.
| | ==[[Cancer historical perspective|Historical Perspective]]== |
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| Nearly all cancers are caused by abnormalities in the [[genome|genetic material]] of the [[malignant transformation|transformed]] cells. These abnormalities may be due to the effects of [[carcinogens]], such as tobacco smoke, [[electromagnetic radiation|radiation]], [[chemicals]], or [[pathogen|infectious agents]]. Other cancer-promoting genetic abnormalities may be randomly acquired through errors in [[DNA replication]], or are [[genetic disorder|inherited]], and thus present in all cells from birth. Complex interactions between carcinogens and the host [[genome]] may explain why only some develop cancer after exposure to a known carcinogen. New aspects of the genetics of cancer pathogenesis, such as [[DNA methylation]], and [[microRNAs]] are increasingly being recognized as important.
| | ==[[Cancer classification|Classification]]== |
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| Genetic abnormalities found in cancer typically affect two general classes of genes. Cancer-promoting ''[[oncogene]]s'' are often activated in cancer cells, giving those cells new properties, such as hyperactive growth and division, protection against [[programmed cell death]], loss of respect for normal tissue boundaries, and the ability to become established in diverse tissue environments. ''[[Tumor suppressor gene]]s'' are often inactivated in cancer cells, resulting in the loss of normal functions in those cells, such as accurate DNA replication, control over the [[cell cycle]], orientation and adhesion within tissues, and interaction with protective cells of the [[immune system]].
| | ==[[Cancer pathophysiology|Pathophysiology]]== |
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| Cancer is usually classified according to the tissue from which the cancerous cells originate, as well as the normal cell type they most resemble. These are location and histology, respectively. A definitive diagnosis usually requires the [[histology|histologic]] examination of a tissue [[biopsy]] specimen by a [[anatomical pathology|pathologist]], although the initial indication of malignancy can be symptoms or [[radiographic]] imaging abnormalities. Most cancers can be treated and some cured, depending on the specific type, location, and [[Cancer staging|stage]]. Once diagnosed, cancer is usually treated with a combination of [[surgery]], [[chemotherapy]] and [[radiation therapy|radiotherapy]]. As research develops, treatments are becoming more specific for different varieties of cancer. There has been significant progress in the development of [[targeted therapy]] drugs that act specifically on detectable molecular abnormalities in certain tumors, and which minimize damage to normal cells. The prognosis of cancer patients is most influenced by the type of cancer, as well as the [[cancer staging|stage]], or extent of the disease. In addition, [[histology|histologic]] [[Grading (tumors)|grading]] and the presence of specific molecular markers can also be useful in establishing prognosis, as well as in determining individual treatments.
| | ==[[Cancer causes|Causes]]== |
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| ==Classification== | | ==[[Cancer differential diagnosis|Differentiating Cancer from other Diseases]]== |
| ===Nomenclature===
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| The following closely related terms may be used to designate abnormal growths:
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| * '''[[Tumor]]:''' originally, it meant any abnormal swelling, lump or mass. In current English, however, the word Tumor has become synonymous with Neoplasm, specifically solid neoplasm. Note that some neoplasms, such as [[Leukemia]], do not form tumors.
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| * '''[[Neoplasia|Neoplasm]]:''' the scientific term to describe an abnormal proliferation of genetically altered cells. Neoplasms can be benign or malignant:
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| ** '''Malignant neoplasm''' or '''malignant tumor''': synonymous with '''cancer'''.
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| ** '''Benign neoplasm''' or '''[[benign tumor]]''': a tumor (solid neoplasm) that stops growing by itself, does not invade other tissues and does not form metastases.
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| * '''Invasive''' tumor is another synonym of '''cancer'''. The name refers to invasion of surrounding tissues.
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| * '''Pre-malignancy''', '''pre-cancer''' or '''non-invasive''' tumor: A neoplasm that is not invasive but has the potential to progress to cancer (become invasive) if left untreated. These lesions are, in order of increasing potential for cancer, [[atypia]], [[dysplasia]] and [[carcinoma in situ]].
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| The following terms can be used to describe a cancer:
| | ==[[Cancer epidemiology and demographics|Epidemiology and Demographics]]== |
| * '''Screening''': a test done on healthy people to detect tumors before they become apparent. A [[mammogram]] is a screening test.
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| * '''Diagnosis''': the confirmation of the cancerous nature of a lump. This usually requires a [[biopsy]] or removal of the tumor by [[surgery]], followed by examination by a [[surgical pathology|pathologist]].
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| * '''Surgical excision''': the removal of a tumor by a [[surgery|surgeon]].
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| ** '''Surgical margins''': the evaluation by a [[surgical pathology|pathologist]] of the edges of the tissue removed by the surgeon to determine if the tumor was removed completely ("negative margins") or if tumor was left behind ("positive margins").
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| * '''Grade]''': a number (usually on a scale of 3) established by a [[surgical pathology|pathologist]] to describe the degree of resemblance of the tumor to the surrounding benign tissue.
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| * '''Stage''': a number (usually on a scale of 4) established by the [[oncology|oncologist]] to describe the degree of invasion of the body by the tumor.
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| * '''Recurrence''': new tumors that appear a the site of the original tumor after surgery.
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| * '''[[Metastasis]]''': new tumors that appear far from the original tumor.
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| * '''Transformation:''' the concept that a low-grade tumor transforms to a high-grade tumor over time. Example: [[Richter's transformation]].
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| * '''Chemotherapy''': treatment with drugs.
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| * '''Radiation therapy''': treatment with radiations.
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| * '''Adjuvant''' therapy: treatment, either chemotherapy or radiation therapy, given after surgery to kill the remaining cancer cells.
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| * '''Prognosis''': the probability of cure after the therapy. It is usually expressed as a probability of survival five years after diagnosis. Alternatively, it can be expressed as the number of years when 50% of the patients are still alive. Both numbers are derived from statistics accumulated with hundreds of similar patients to give a [[Kaplan-Meier estimator|Kaplan-Meier curve]].
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| Cancers are classified by the type of cell that resembles the tumor and, therefore, the tissue presumed to be the origin of the tumor. Examples of general categories include:
| | ==[[Cancer risk factors|Risk Factors]]== |
| * '''[[Carcinoma]]:''' Malignant tumors derived from [[epithelium|epithelial]] cells. This group represents the most common cancers, including the common forms of [[breast cancer|breast]], [[prostate cancer|prostate]], [[lung cancer|lung]] and [[Colorectal cancer|colon cancer]].
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| * '''[[Sarcoma]]:''' Malignant tumors derived from [[connective tissue]], or [[mesenchyme|mesenchymal]] cells.
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| * '''[[Lymphoma]]''' and '''[[leukemia]]:''' Malignancies derived from hematopoietic ([[blood]]-forming) cells
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| * '''[[Germ cell tumor]]:''' Tumors derived from [[totipotent]] cells. In adults most often found in the [[testicle]] and [[ovary]]; in fetuses, babies, and young children most often found on the body midline, particularly at the tip of the tailbone; in horses most often found at the poll (base of the skull).
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| * '''Blastic tumor:''' A tumor (usually malignant) which resembles an immature or embryonic tissue. Many of these tumors are most common in children.
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| Malignant tumors (cancers) are usually named using '''-carcinoma''', '''-sarcoma''' or '''-blastoma''' as a suffix, with the Latin or Greek word for the organ of origin as the root. For instance, a cancer of the liver is called ''[[hepatocarcinoma]]''; a cancer of the fat cells is called ''liposarcoma''. For common cancers, the English organ name is used. For instance, the most common type of [[breast cancer]] is called ''ductal carcinoma of the breast'' or ''mammary ductal carcinoma''. Here, the adjective ''ductal'' refers to the appearance of the cancer under the microscope, resembling normal breast ducts.
| | ==[[Cancer screening|Screening]]== |
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| [[Benign tumor]]s are named using '''-oma''' as a suffix with the organ name as the root. For instance, a benign tumor of the smooth muscle of the uterus is called ''leiomyoma'' (the common name of this frequent tumor is ''fibroid''). Unfortunately, some cancers also use the '''-oma''' suffix, examples being [[melanoma]] and [[seminoma]]. | | ==[[Cancer natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
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| ===Adult cancers=== | | ==Diagnosis== |
| In the U.S. and other developed countries, cancer is presently responsible for about 25% of all deaths.<ref name="CACancerJClin2005-Jemal">
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| {{cite journal | author=Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, Feuer EJ, Thun MJ | title=Cancer statistics, 2005 | journal=CA Cancer J Clin | year=2005 | pages=10-30 | volume=55 | issue=1 | url=http://caonline.amcancersoc.org/cgi/content/full/55/1/10 | id=PMID 15661684}}</ref> On a yearly basis, 0.5% of the population is diagnosed with cancer. The statistics below are for adults in the United States, and may vary substantially in other countries:
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| {| class="wikitable"
| | [[Cancer history and symptoms|History and Symptoms ]] | [[ Cancer physical examination|Physical Examination]] | [[Cancer laboratory findings|Laboratory Findings]] | [[Cancer electrocardiogram|Electrocardiogram]] | [[Cancer chest x ray|Chest X Ray]] | [[Cancer CT|CT]] | [[Cancer MRI|MRI]] | [[Cancer echocardiography or ultrasound|Echocardiography or Ultrasound]] | [[Cancer other imaging findings|Other Imaging Findings]] | [[Cancer other diagnostic studies|Other Diagnostic Studies]] |
| ! colspan="2" | <big>Male</big>
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| ! colspan="2" | <big>Female</big>
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| ! width="170px" | most common (by occurrence) !! width="170px" | most common (by mortality) <ref name="CACancerJClin2005-Jemal" />
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| ! width="170px" | most common (by occurrence)!! width="170px" | most common (by mortality) <ref name="CACancerJClin2005-Jemal" />
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| |[[prostate cancer]] (33%) || lung cancer (31%) || [[breast cancer]] (32%) || lung cancer (27%)
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| | [[lung cancer]] (13%) || prostate cancer (10%) || lung cancer (12%) || breast cancer (15%) | |
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| | [[colorectal cancer]] (10%) || colorectal cancer (10%) || colorectal cancer (11%) || colorectal cancer (10%) | |
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| | [[bladder cancer]] (7%) || [[pancreatic cancer]] (5%) || [[endometrial cancer]] (6%) || [[ovarian cancer]] (6%) | |
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| | cutaneous [[melanoma]] (5%) || [[leukemia]] (4%) || [[non-Hodgkin lymphoma]] (4%) || pancreatic cancer (6%) | |
| |}
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| ===Childhood cancers=== | | ==Treatment== |
| Cancer can also occur in young children and adolescents, but it is rare (about 150 cases per million yearly in the US). Statistics from the SEER program of the US [[National Cancer Institute|NCI]] demonstrate that childhood cancers increased 19% between 1975 and 1990, mainly due to an increased incidence in [[acute leukemia]]. Since 1990, incidence rates have decreased <ref>''Cancer Incidence and Survival among Children and Adolescents, United States SEER program 1975-1995'', available online from the [http://www.seer.cancer.gov/publications/childhood/ SEER web site]</ref> | | [[Cancer medical therapy|Medical Therapy]] | [[Cancer surgery |Surgery]] | [[Cancer social impact|Social Impact]] | [[Cancer primary prevention|Primary Prevention]] | [[Cancer secondary prevention|Secondary Prevention]] | [[Cancer cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Cancer future or investigational therapies|Future or Investigational Therapies]] |
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| The age of peak incidence of cancer in children occurs during the first year of life. [[Leukemia]] (usually [[Acute lymphoblastic leukemia|ALL]]) is the most common infant malignancy (30%), followed by the [[brain tumor|central nervous system cancers]] and [[neuroblastoma]]. The remainder consists of [[Wilms' tumor]], [[lymphoma]]s, [[rhabdomyosarcoma]] (arising from muscle), [[retinoblastoma]], [[osteosarcoma]] and [[Ewing's sarcoma]].<ref name="CACancerJClin2005-Jemal" /> [[Teratoma]] is the most common tumor in this age group, but most teratomas are surgically removed while still benign, hence not necessarily cancer.
| | ==Case Studies== |
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| 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.
| | [[Cancer case study one|Case #1]] |
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| == Signs and symptoms == | | ==Related Chapters== |
| Roughly, cancer symptoms can be divided into three groups:
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| * ''Local symptoms'': unusual lumps or swelling (''[[tumor]]''), [[hemorrhage]] (bleeding), [[Pain and nociception|pain]] and/or [[ulcer]]ation. Compression of surrounding tissues may cause symptoms such as [[jaundice]] (yellowing the eyes and skin).
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| * ''Symptoms of [[metastasis]] (spreading)'': enlarged [[lymph node]]s, [[cough]] and [[hemoptysis]], [[hepatomegaly]] (enlarged [[liver]]), bone pain, [[fracture]] of affected bones and [[neurology|neurological]] symptoms. Although advanced cancer may cause [[Pain and nociception|pain]], it is often not the first symptom.
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| * ''Systemic symptoms'': [[weight loss]], [[anorexia (symptom)|poor appetite]], [[fatigue]] and [[cachexia]] ([[wasting]]), excessive [[sweating]] ([[sleep hyperhidrosis|night sweats]]), [[anemia]] and specific [[paraneoplastic phenomenon|paraneoplastic phenomena]], i.e. specific conditions that are due to an active cancer, such as [[thrombosis]] or hormonal changes.
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| Every symptom in the above list can be caused by a variety of conditions (a list of which is referred to as the [[differential diagnosis]]). Cancer may be a common or uncommon cause of each item.
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| == Diagnosis ==
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| 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 [[anatomical pathology|pathologist]].
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| === Investigation ===
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| [[Image:Thorax pa peripheres Bronchialcarcinom li OF markiert.jpg|thumb|Chest x-ray showing lung cancer in the left lung.|right]]
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| People with suspected cancer are investigated with [[medical test]]s. These commonly include [[blood test]]s, [[X-ray]]s, [[CT scan]]s and [[endoscopy]].
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| === Biopsy ===
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| A cancer may be suspected for a variety of reasons, but the definitive diagnosis of most malignancies must be confirmed by [[histology|histological]] examination of the cancerous cells by a [[anatomical pathology|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]].
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| 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.
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| == Treatment ==
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| 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 [[Cancer staging|stage]] of the disease, as well as the general state of the patient ([[performance status]]). A number of [[experimental cancer treatment]]s are also under development.
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| 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.
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| 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 disease]]s.
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| === Surgery ===
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| In theory, non-[[hematological]] cancers can be cured if entirely removed by [[surgery]], but this is not always possible. When the cancer has [[metastasis|metastasized]] to other sites in the body prior to surgery, complete surgical excision is usually impossible. In the [[Halsted]]ian model of cancer progression, tumors grow locally, then spread to the lymph nodes, then to the rest of the body. This has given rise to the popularity of local-only treatments such as surgery for small cancers. Even small localized tumors are increasingly recognized as possessing metastatic potential.
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| 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 [[anatomical pathology|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.
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| In addition to removal of the primary tumor, surgery is often necessary for [[cancer staging|staging]], e.g. determining the extent of the disease and whether it has [[metastasis|metastasized]] to regional [[lymph node]]s. Staging is a major determinant of [[prognosis]] and of the need for [[adjuvant therapy]].
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| Occasionally, surgery is necessary to control symptoms, such as [[spinal cord compression]] or [[bowel obstruction]]. This is referred to as [[palliative treatment]].
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| === Radiation therapy ===
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| {{main|Radiation therapy}}
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| [[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.
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| 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.
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| === Chemotherapy ===
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| {{main|Chemotherapy}}
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| [[Chemotherapy]] is the treatment of cancer with [[medication|drugs]] ("anticancer drugs") that can destroy cancer cells. In current usage, the term "chemotherapy" usually refers to ''cytotoxic'' drugs which affect rapidly dividing cells in general, in contrast with ''targeted therapy'' (see below). Chemotherapy drugs interfere with cell division in various possible ways, e.g. with the duplication of [[DNA]] or the separation of newly formed [[chromosome]]s. Most forms of chemotherapy target all rapidly dividing cells and are not specific for cancer cells, although some degree of specificity may come from the inability of many cancer cells to repair DNA damage, while normal cells generally can. 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.
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| 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.
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| The treatment of some [[leukaemia]]s and [[lymphoma]]s requires the use of high-dose chemotherapy, and [[total body irradiation]] (TBI). 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 [[stem cell transplantation]]. Alternatively, [[hematopoietic stem cells]] may be transplanted from a matched unrelated donor (MUD).
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| === Targeted therapies ===
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| {{main|Targeted therapy}}
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| 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 molecule targeted therapy drugs are generally inhibitors of [[enzyme|enzymatic]] domains on mutated, overexpressed, or otherwise critical proteins within the cancer cell. Prominent examples are the tyrosine kinase inhibitors [[imatinib]] and [[gefitinib]].
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| [[Monoclonal antibody therapy]] is another strategy in which the therapeutic agent is an [[antibody]] which specifically binds to a protein on the surface of the cancer cells. Examples include the anti-[[HER2/neu]] antibody [[trastuzumab]] (Herceptin®) used in breast cancer, and the anti-CD20 antibody [[rituximab]], used in a variety of [[B-cell]] malignancies.
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| [[Targeted therapy]] can also involve small [[peptide]]s as "homing devices" 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. Especially oligo- or multimers of these binding motifs are of great interest, since this can lead to enhanced tumor specificity and avidity.
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| [[Photodynamic therapy]] (PDT) is a ternary treatment for cancer involving a photosensitizer, tissue oxygen, and light (often using lasers). PDT can be used as treatment for [[basal cell carcinoma]] (BCC) or [[lung cancer]]; PDT can also be useful in removing traces of malignant tissue after surgical removal of large tumors.<ref>{{cite journal |last=Dolmans |first=DE |coauthors=Fukumura D, Jain RK |year=2003 |month=May |title=Photodynamic therapy for cancer |journal=Nat Rev Cancer |volume=3 |issue=5 |pages=380-7 |id=PMID 12724736 |url=http://www.nature.com/nrc/journal/v3/n5/abs/nrc1071_fs.html}}</ref>
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| === Immunotherapy ===
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| {{main|Cancer immunotherapy}}
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| Cancer immunotherapy refers to a diverse set of therapeutic strategies designed to induce the patient's own [[immune system]] to fight the tumor. Contemporary methods for generating an immune response against tumours include intravesical [[Bacillus Calmette-Guérin|BCG]] immunotherapy for superficial bladder cancer, and use of [[interferon]]s and other [[cytokine]]s to induce an immune response in [[renal cell carcinoma]] and [[melanoma]] patients. [[Vaccine]]s to generate specific [[immune response]]s are the subject of intensive research for a number of tumours, notably [[malignant melanoma]] and [[renal cell carcinoma]]. [[Sipuleucel-T]] is a vaccine-like strategy in late clinical trials for [[prostate cancer]] in which [[dendritic cell]]s from the patient are loaded with [[prostatic acid phosphatase]] peptides to induce a specific immune response against prostate-derived cells.
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| Allogeneic [[hematopoietic stem cell transplantation]] ("bone marrow transplantation" from a genetically non-identical donor) can be considered a form of immunotherapy, since the donor's immune cells will often attack the tumor in a phenomenon known as [[Hematopoietic stem cell transplantation#Side effects and complications|graft-versus-tumor effect]]. For this reason, allogeneic HSCT leads to a higher cure rate than autologous transplantation for several cancer types, although the side effects are also more severe.
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| === Hormonal therapy ===
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| {{main|Hormonal therapy (oncology)}}
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| 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. In certain cancers, administration of hormone agonists, such as [[progestogen]]s may be therapeutically beneficial.
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| === Symptom control ===
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| 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 doctors generally have the therapeutic skills to reduce 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.
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| [[analgesia|Pain medication]], such as [[morphine]] and [[oxycodone]], and [[antiemetic]]s, drugs to suppress nausea and vomiting, are very commonly used in patients with cancer-related symptoms. Improved [[antiemetic]]s such as [[ondansetron]] and analogues, as well as [[aprepitant]] have made aggressive treatments much more feasible in cancer patients.
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| [[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. Doctors have been reluctant to prescribe narcotics for pain in terminal cancer patients, for fear of contributing to addiction or suppressing respiratory function. The [[palliative care]] movement, a more recent offshoot of the [[hospice]] movement, has engendered more widespread support for preemptive pain treatment for cancer patients.
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| [[Fatigue]] is a very common problem for cancer patients, and has only recently become important enough for oncologists to suggest treatment, even though it plays a significant role in many patients' quality of life.
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| === Complementary and alternative ===
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| [[Alternative medicine|Complementary and alternative medicine]] (CAM) treatments are the diverse group of medical and health care systems, practices, and products that are not part of conventional medicine.<ref name="mnalt">{{cite web |url=http://www.mnwelldir.org/docs/cancer1/altthrpy.htm | title = Alternative Cancer Therapies | publisher = Minnesota Wellness Directory |accessdate=2007-11-05}}</ref> [[Oncology]], the study of human cancer, has a long history of incorporating unconventional or botanical treatments into mainstream cancer therapy. Some examples of this phenomenon include the [[chemotherapy agent]] [[paclitaxel]], which is derived from the bark of the [[Taxus brevifolia|Pacific Yew tree]], and [[ATRA]], all-trans retinoic acid, a derivative of [[Vitamin A]] that induces cures in an aggressive [[leukemia]] known as [[acute promyelocytic leukemia]]. Many "complementary" and "alternative" medicines for cancer have not been studied using the [[scientific method]], such as in well-designed [[clinical trials]], or they have only been studied in preclinical (animal or [[in-vitro]]) laboratory studies. Many times, "complementary" and "alternative" medicines are supported by marketing materials and "testimonials" from users of the substances. Frequently, when these treatments are subjected to rigorous scientific testing, they are found not to work. A recent example was reported at the 2007 annual meeting of the [[American Society of Clinical Oncology]]: a [[Clinical trial#Phase III|Phase III]] clinical trial comparing shark cartilage extract to [[placebo]] in [[Lung cancer#Non-small cell lung carcinoma .28NSCLC.29|non-small cell lung cancer]] demonstrated no benefit of the shark cartilage extract, AE-491.<ref>{{cite web |url=http://www.sciencedaily.com/releases/2007/06/070603215346.htm |title=ScienceDaily: Shark Cartilage Shows No Benefit As A Therapeutic Agent For Lung Cancer |accessdate=2007-06-04 |format= |work=}}</ref>
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| "Complementary medicine" refers to methods and substances used along with conventional medicine, while "alternative medicine" refers to compounds used instead of conventional medicine. A study of CAM use in patients with cancer in the July 2000 issue of the Journal of Clinical Oncology found that 69% of 453 cancer patients had used at least one CAM therapy as part of their cancer treatment.<ref name=NCCAM>{{cite web | title= National Center for Complementary and Alternative Medicine's Cancer FAQ | url=http://nccam.nih.gov/health/camcancer/| accessdate=2007-03-01}}</ref>
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| Some ''complementary'' measures include [[botanical medicine]], such as an [[NIH]] trial currently underway testing mistletoe extract combined with [[chemotherapy]] for the treatment of solid tumors, [[acupuncture]] for managing chemotherapy-associated nausea and vomiting and in controlling pain associated with surgery, psychological approaches such as "[[Cancer guided imagery|imaging]]" or [[meditation]] to aid in pain relief or improve mood.<ref name=NCCAM/>
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| 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. Some people resort to these so-called "alternative" forms of treatment in desperation or as a last resort. However, no alternative therapies have been shown in any scientific study to effectively treat cancer. Some express the view that the promotion and sale of certain alternative modalities known to be ineffective constitute [[quackery]].<ref>{{cite web | title=A Special Message to Cancer Patients Seeking "Alternative" Treatments | url=http://www.quackwatch.org/00AboutQuackwatch/altseek.html | accessdate=2005-12-16}}</ref>
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| === Treatment trials ===
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| [[Clinical trial]]s, 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]].
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| 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.
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| 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.
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| == Prognosis ==
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| 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]].
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| 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.
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| Cancer patients, for the first time in the history of oncology, are visibly returning to the athletic arena and workplace. Patients are living longer with either quiescent persistent disease or even complete, durable remissions. The stories of Lance Armstrong, who won the Tour de France after treatment for [[metastatic]] [[testicular cancer]], or Tony Snow, who was working as the White House Press Secretary as of June, 2007 despite relapsed [[Colorectal cancer|colon cancer]], continue to be an inspiration to cancer patients everywhere.
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| === Emotional impact ===
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| Many local organizations offer a variety of practical and support services to people with cancer. Support can take the form of [[Cancer support group|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.
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| 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, peer counseling, bereavement, patient-to-patient, and sexuality.
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| 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.
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| == Causes ==
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| {{main|Carcinogenesis}}
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| Cancer is a diverse class of diseases which differ widely in their causes and biology. The common thread in all known cancers is the acquisition of abnormalities in the genetic material of the cancer cell and its progeny. Research into the pathogenesis of cancer can be divided into three broad areas of focus. The first area of research focuses on the agents and events which cause or facilitate genetic changes in cells destined to become cancer. Second, it is important to uncover the precise nature of the genetic damage, and the genes which are affected by it. The third focus is on the consequences of those genetic changes on the biology of the cell, both in generating the defining properties of a cancer cell, and in facilitating additional genetic events, leading to further progression of the cancer.
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| === Chemical carcinogens ===
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| Cancer pathogenesis is traceable back to [[DNA mutations]] that impact cell growth and metastasis. Substances that cause [[DNA mutations]] are known as mutagens, and mutagens that cause cancers are known as carcinogens. Particular substances have been linked to specific types of cancer. [[Tobacco smoking]] is associated with [[lung cancer]] and [[bladder cancer]]. Prolonged exposure to [[asbestos]] fibers is associated with [[mesothelioma]].
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| Many [[mutagen]]s are also [[carcinogen]]s, but some carcinogens are not mutagens. [[Alcohol]] is an example of a chemical carcinogen that is not a mutagen. Such chemicals are thought to promote cancers through their stimulating effect on the rate of cell [[mitosis]]. Faster rates of mitosis leaves less time 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]] (''see [[aneuploidy]] above'').
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| [[Image:Cancer smoking lung cancer correlation from NIH.svg|thumb|300px|right|The incidence of lung cancer is highly correlated with smoking. Source:NIH.]]
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| Decades of research have demonstrated the strong association between [[tobacco]] use and cancers of many sites, making it perhaps the most important human carcinogen. 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 [[tobacco smoking|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.
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| === Ionizing radiation ===
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| Sources of [[ionizing radiation]], such as [[radon]] gas, can cause cancer. Prolonged exposure to [[ultraviolet radiation]] from the sun can lead to [[melanoma]] and other skin malignancies.
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| === Infectious diseases ===
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| Furthermore, many cancers originate from a [[virus|viral]] [[infection]]; this is especially true in animals such as birds, but also in [[human]]s, as viruses are responsible for 15% of human cancers worldwide. The main viruses associated with human cancers are [[human papillomavirus]], [[hepatitis B]] and [[hepatitis C]] virus, [[Epstein-Barr virus]], and [[human T-lymphotropic virus]]. Experimental and epidemiological data imply a causative role for viruses and they appear to be the second most important risk factor for cancer development in humans, exceeded only by tobacco usage.<ref name="zur Hausen-viruses">{{cite journal | author = zur Hausen H | title = Viruses in human cancers. | journal = Science | volume = 254 | issue = 5035 | pages = | year = 1991 | id = PMID}}</ref> 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 [[retrovirus]]es, 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.
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| Hepatitis viruses, including [[hepatitis B]] and [[hepatitis C]], can induce a chronic viral infection that leads to [[Hepatocellular carcinoma|liver cancer]] in 0.47% of [[hepatitis B]] patients per year (especially in Asia, less so in North America), and in 1.4% of [[hepatitis C]] carriers per year. Liver cirrhosis, whether from chronic viral hepatitis infection or alcoholism, is associated with the development of [[Hepatocellular carcinoma|liver cancer]], and the combination of cirrhosis and viral hepatitis presents the highest risk of [[Hepatocellular carcinoma|liver cancer]] development. Worldwide, [[Hepatocellular carcinoma|liver cancer]] is one of the most common, and most deadly, cancers due to a huge burden of [[viral hepatitis]] transmission and disease.
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| Advances in cancer research have made a vaccine designed to prevent cancer available. In 2006, the US [[FDA]] approved a [[human papilloma virus]] vaccine, called [[Gardasil]]®. The vaccine protects against four HPV types, which together cause 70% of cervical cancers and 90% of genital warts. In March 2007, the US [[Centers for Disease Control and Prevention|CDC]] [[Advisory Committee on Immunization Practices]] (ACIP) officially recommended that females aged 11-12 receive the vaccine, and indicated that females as young as age 9 and as old as age 26 are also candidates for immunization.
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| In addition to viruses, researchers have noted a connection between bacteria and certain cancers. The most prominent example is the link between chronic infection of the wall of the stomach with ''[[Helicobacter pylori]]'' and [[gastric cancer]].<ref>{{cite journal |author=Peter S, Beglinger C |title=Helicobacter pylori and gastric cancer: the causal relationship |journal=Digestion |volume=75 |issue=1 |pages=25-35 |year=2007 |pmid=17429205 |doi=10.1159/000101564}}</ref>
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| === Hormonal imbalances ===
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| Some hormones can act in a similar manner to non-mutagenic carcinogens in that they may stimulate excessive cell growth. A well-established example is the role of [[estrogen|hyperestrogenic]] states in promoting [[endometrial cancer]].
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| === Immune system dysfunction ===
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| [[HIV]] is associated with a number of malignancies, including [[Kaposi's sarcoma]], [[non-Hodgkin's lymphoma]], and [[HPV]]-associated malignancies such as [[anal cancer]] and [[cervical cancer]]. [[AIDS]]-defining illnesses have long included these diagnoses. The increased incidence of malignancies in HIV patients points to the breakdown of immune surveillance as a possible etiology of cancer.<ref>{{cite journal |author=Wood C, Harrington W |title=AIDS and associated malignancies |journal=Cell Res. |volume=15 |issue=11-12 |pages=947-52 |year=2005 |pmid=16354573 |doi=10.1038/sj.cr.7290372}}</ref> Certain other immune deficiency states (e.g. [[common variable immunodeficiency]] and [[IgA deficiency]]) are also associated with increased risk of malignancy.<ref>{{cite journal |author=Mellemkjaer L, Hammarstrom L, Andersen V, ''et al'' |title=Cancer risk among patients with IgA deficiency or common variable immunodeficiency and their relatives: a combined Danish and Swedish study |journal=Clin. Exp. Immunol. |volume=130 |issue=3 |pages=495-500 |year=2002 |pmid=12452841 |doi=}}</ref>
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| === Heredity ===
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| Most forms of cancer are "sporadic", and have no basis in heredity. There are, however, a number of recognised [[syndrome]]s of cancer with a hereditary component, often a defective tumor suppressor [[allele]]. Famous examples are:
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| * certain inherited mutations in the genes ''[[BRCA1]]'' and ''[[Lung cancer#Non-small cell lung carcinoma .28NSCLC.29|BRCA2]]'' are associated with an elevated risk of [[breast cancer]] and [[ovarian cancer]]
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| * tumors of various endocrine organs in [[multiple endocrine neoplasia]] (MEN types 1, 2a, 2b)
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| * [[Li-Fraumeni syndrome]] (various tumors such as [[osteosarcoma]], breast cancer, [[soft tissue sarcoma]], [[brain tumor]]s) due to mutations of [[p53]]
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| * [[Turcot syndrome]] ([[brain tumor]]s and colonic polyposis)
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| * [[Familial adenomatous polyposis]] an inherited mutation of the ''APC'' gene that leads to early onset of [[colon carcinoma]].
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| * [[Hereditary nonpolyposis colorectal cancer]] (HNPCC, also known as Lynch syndrome) can include familial cases of [[Colorectal cancer|colon cancer]], uterine cancer, [[gastric cancer]], and [[ovarian cancer]], without a preponderance of [[Polyp (medicine)|colon polyps]].
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| * [[Retinoblastoma]], when occurring in young children, is due to a hereditary mutation in the retinoblastoma gene.
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| * [[Down syndrome]] patients, who have an extra [[chromosome 21]], are known to develop malignancies such as [[leukemia]] and [[testicular cancer]], though the reasons for this difference are not well understood.
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| === Other causes ===
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| A few types of cancer in non-humans have been found to be caused by the tumor cells themselves. This phenomenon is seen in Sticker's sarcoma, also known as canine transmissible venereal tumor.<ref>{{cite journal |author=Murgia C, Pritchard JK, Kim SY, Fassati A, Weiss RA |title=Clonal origin and evolution of a transmissible cancer |journal=Cell |volume=126 |issue=3 |pages=477-87 |year=2006 |pmid=16901782}}</ref> The closest known analogue to this in humans is individuals who have developed cancer from tumors hiding inside organ transplants.
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| == Pathophysiology ==
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| [[Image:Cancer requires multiple mutations from NIH.png|thumb|150px|right|Cancers are caused by a series of mutations. Each mutation alters the behavior of the cell somewhat.]]
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| Cancer is fundamentally a disease of regulation of tissue growth. In order for a normal cell to [[malignant transformation|transform]] into a cancer cell, [[genes]] which regulate cell growth and differentiation must be altered. Genetic changes can occur at many levels, from gain or loss of entire chromosomes to a mutation affecting a [[Single nucleotide polymorphism|single DNA nucleotide]]. There are two broad categories of genes which are affected by these changes. [[Oncogene]]s may be normal genes which are expressed at inappropriately high levels, or altered genes which have novel properties. In either case, expression of these genes promotes the malignant phenotype of cancer cells. [[Tumor suppressor gene]]s are genes which inhibit cell division, survival, or other properties of cancer cells. Tumor suppressor genes are often disabled by cancer-promoting genetic changes. Typically, changes in many genes are required to transform a normal cell into a cancer cell.
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| There is a diverse classification scheme for the various genomic changes which may contribute to the generation of cancer cells. Most of these changes are [[mutation]]s, or changes in the [[nucleotide]] sequence of genomic DNA. [[Aneuploidy]], the presence of an abnormal number of chromosomes, is one genomic change which is not a mutation, and may involve either gain or loss of one or more [[chromosomes]] through errors in [[mitosis]].
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| Large-scale mutations involve the deletion or gain of a portion of a chromosome. [[Gene amplification|Genomic amplification]] occurs when a cell gains many copies (often 20 or more) of a small chromosomal locus, usually containing one or more oncogenes and adjacent genetic material. [[Chromosomal translocation|Translocation]] occurs when two separate chromosomal regions become abnormally fused, often at a characteristic location. A well-known example of this is the [[Philadelphia chromosome]], or translocation of chromosomes 9 and 22, which occurs in [[chronic myelogenous leukemia]], and results in production of the [[BCR gene|BCR]]-[[Abl gene|abl]] [[fusion protein]], an oncogenic [[tyrosine kinase]].
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| Small-scale mutations include point mutations, deletions, and insertions, which may occur in the [[promoter]] of a gene and affect its [[gene expression|expression]], or may occur in the gene's [[coding sequence]] and alter the function or stability of its [[protein]] product. Disruption of a single gene may also result from [[provirus|integration of genomic material]] from a [[DNA virus]] or [[retrovirus]], and such an event may also result in the expression of viral oncogenes in the affected cell and its descendants.
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| ===Epigenetics===
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| [[Epigenetic]]s is the study of the regulation of gene expression through chemical, non-mutational changes in DNA structure. The theory of [[epigenetics]] in cancer pathogenesis is that non-mutational changes to DNA can lead to alterations in gene expression. Normally, [[oncogenes]] are silent, for example, because of [[DNA methylation]]. Loss of that methylation can induce the aberrant expression of [[oncogenes]], leading to cancer pathogenesis. Known mechanisms of epigenetic change include [[DNA methylation]], and methylation or acetylation of [[histone]] proteins bound to chromosomal DNA at specific locations. Classes of medications, known as [[HDAC inhibitors]] and DNA methyltransferase inhibitors, can re-regulate the epigenetic signaling in the cancer cell.
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| === Oncogenes ===
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| [[Oncogenes]] promote cell growth through a variety of ways. Many can produce [[hormone]]s, a "chemical messenger" between cells which encourage [[mitosis]], the effect of which depends on the [[signal transduction]] of the receiving tissue or cells. In other words, when a hormone receptor on a recipient cell is stimulated, the signal is conducted from the surface of the cell to the [[cell nucleus]] to effect some change in gene transcription regulation at the nuclear level. Some oncogenes are part of the signal transduction system itself, or the signal [[receptor (biochemistry)|receptors]] in cells and tissues themselves, thus controlling the sensitivity to such hormones. Oncogenes often produce [[mitogen]]s, or are involved in [[transcription (genetics)|transcription]] of DNA in [[protein biosynthesis|protein synthesis]], which creates the [[protein]]s and [[enzyme]]s responsible for producing the products and [[biochemistry|biochemicals]] cells use and interact with.
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| Mutations in proto-oncogenes, which are the normally quiescent counterparts of [[oncogenes]], can modify their [[gene expression|expression]] and function, increasing the amount or activity of the product protein. When this happens, the proto-oncogenes become [[oncogene]]s, and this transition upsets the normal balance of [[cell cycle]] regulation in the cell, making uncontrolled growth possible. The chance of cancer cannot be reduced by removing proto-oncogenes from the [[genome]], even if this were possible, as they are critical for growth, repair and [[homeostasis]] of the organism. It is only when they become mutated that the signals for growth become excessive.
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| One of the first [[oncogenes]] to be defined in cancer research is the [[ras oncogene]]. Mutations in the Ras family of [[proto-oncogene]]s (comprising H-Ras, N-Ras and K-Ras) are very common, being found in 20% to 30% of all human tumours.<ref>{{cite journal | author=Bos J | title=ras oncogenes in human cancer: a review. | journal=Cancer Res | volume=49 | issue=17 | pages=4682-9 | year=1989 | id=PMID 2547513}}</ref> Ras was originally identified in the Harvey sarcoma virus genome, and researchers were surprised that not only was this gene present in the human genome but that, when ligated to a stimulating control element, could induce cancers in cell line cultures.<ref name="pmid6283358">{{cite journal |author=Chang EH, Furth ME, Scolnick EM, Lowy DR |title=Tumorigenic transformation of mammalian cells induced by a normal human gene homologous to the oncogene of Harvey murine sarcoma virus |journal=Nature |volume=297 |issue=5866 |pages=479-83 |year=1982 |pmid=6283358 |doi=}}</ref>
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| === Tumor suppressor genes ===
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| [[Tumor suppressor gene]]s code for anti-proliferation signals and proteins that suppress mitosis and cell growth. Generally, tumor suppressors are [[transcription factor]]s that are activated by cellular [[stress (medicine)|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 the cell cycle in order to carry out DNA repair, preventing mutations from being passed on to daughter cells. The [[p53]] protein, one of the most important studied tumor suppressor genes, is a transcription factor activated by many cellular stressors including [[Hypoxia (medical)|hypoxia]] and [[ultraviolet radiation]] damage.
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| Despite nearly half of all cancers possibly involving alterations in p53, its tumor suppressor function is poorly understood. p53 clearly has two functions: one a nuclear role as a transcription factor, and the other a cytoplasmic role in regulating the cell cycle, cell division, and apoptosis.
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| The [[Warburg hypothesis]] is the preferential use of glycolysis for energy to sustain cancer growth. p53 has been shown to regulate the shift from the respiratory to the glycolytic pathway.<ref name="Mantoba-Warburg">{{cite journal | author = Matoba S, Kang J, Patino W, Wragg A, Boehm M, Gavrilova O, Hurley P, Bunz F, Hwang P | title = p53 regulates mitochondrial respiration. | journal = Science | volume = 312 | issue = 5780 | pages = 1650-3 | year = 2006 | id = PMID 16728594}}</ref>
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| 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.
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| Mutations of tumor suppressor genes that occur in [[germline]] cells are passed along to [[offspring]], and increase the likelihood for cancer diagnoses in subsequent generations. Members of these families have increased incidence and decreased latency of multiple tumors. The tumor types are typical for each type of tumor suppressor gene mutation, with some mutations causing particular cancers, and other mutations causing others. The mode of inheritance of mutant tumor suppressors is that an affected member inherits a defective copy from one parent, and a normal copy from the other. For instance, individuals who inherit one mutant ''[[p53]]'' allele (and are therefore [[heterozygote|heterozygous]] for mutated ''p53'') can develop [[melanomas]] and [[pancreatic cancer]], known as [[Li-Fraumeni syndrome]]. Other inherited tumor suppressor gene syndromes include ''[[Retinoblastoma protein|Rb]]'' mutations, linked to [[retinoblastoma]], and ''[[Familial adenomatous polyposis#Pathophysiology|APC]]'' gene mutations, linked to [[Familial adenomatous polyposis|adenopolyposis colon cancer]]. Adenopolyposis colon cancer is associated with thousands of polyps in colon while young, leading to [[Colorectal cancer|colon cancer]] at a relatively early age. Finally, inherited mutations in ''[[BRCA1]]'' and ''[[BRCA2]]'' lead to early onset of [[breast cancer]].
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| Development of cancer was proposed in 1971 to depend on at least two mutational events. In what became known as the [[Alfred G. Knudson|Knudson]] [[Knudson hypothesis|two-hit hypothesis]], an inherited, germ-line mutation in a [[tumor suppressor gene]] would only cause cancer if another mutation event occurred later in the organism's life, inactivating the other [[allele]] of that [[tumor suppressor gene]].<ref>{{cite journal |author=Knudson A |title=Mutation and cancer: statistical study of retinoblastoma |journal=Proc Natl Acad Sci U S A |volume=68 |issue=4 |pages=820-3 |year=1971 |id=PMID 5279523}}</ref>
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| Usually, oncogenes are [[dominant gene|dominant]], as they contain [[Mutation#By effect on function|gain-of-function mutation]]s, while mutated tumor suppressors are [[recessive gene|recessive]], as they contain [[Mutation#By effect on function|loss-of-function mutation]]s. Each cell has two copies of the same gene, one from each parent, and under most cases gain of function mutations in just one copy of a particular proto-oncogene is enough to make that gene a true oncogene. On the other hand, loss of function mutations need to happen in both copies of a tumor suppressor gene to render that gene completely non-functional. However, cases exist in which one mutated copy of a [[tumor suppressor gene]] can render the other, [[wild-type]] copy non-functional. This phenomenon is called the ''dominant negative effect'' and is observed in many p53 mutations.
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| 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.<ref name="Fodde-Haploinsufficiency">{{cite journal | author = Fodde R, Smits R | title = Cancer biology. A matter of dosage. | journal = Science | volume = 298 | issue = 5594 | pages = 761-3 | year = 2002 | id = PMID 12399571}}</ref>
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| === Cancer cell biology ===
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| [[Image:Cancer progression from NIH.png|thumb|250px|left|Tissue can be organized in a continuous spectrum from normal to cancer.|right]]
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| Often, the multiple genetic changes which result in cancer may take many years to accumulate. During this time, the biological behavior of the pre-malignant cells slowly change from the properties of normal cells to cancer-like properties. Pre-malignant tissue can have a distinctive appearance under the [[microscope]]. Among the distinguishing traits are an increased number of dividing cells, variation in [[cell nucleus|nuclear]] size and shape, variation in cell size and shape, loss of specialized cell features, and loss of normal tissue organization. [[Dysplasia]] is an abnormal type of excessive cell proliferation characterized by loss of normal tissue arrangement and cell structure in pre-malignant cells. These early neoplastic changes must be distinguished from hyperplasia, a reversible increase in cell division caused by an external stimulus, such as a hormonal imbalance or chronic irritation.
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| 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 has not shown invasion into other tissues. Nevertheless, carcinoma in situ may develop into an invasive malignancy and is usually removed surgically, if possible.
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| ==== Clonal evolution ====
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| The process of malignancy can be explained from an evolutionary perspective. Millions of years of biological [[evolution]] insure that the cellular metabolic changes that enable cancer to grow occur only very rarely. Most changes in cellular metabolism that allow cells to grow in a disorderly fashion lead to cell death. Cancer cells undergo a process analogous to [[natural selection]], in that the few cells with new genetic changes that enhance their survival continue to multiply, and soon come to dominate the growing tumor, as cells with less favorable genetic change are outcompeted. This process is called clonal evolution. Tumors often continue to evolve in response to chemotherapy treatments, and on occasion aberrant cells may acquire resistance to particular anti-cancer pharmaceuticals.
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| ==== Biological properties of cancer cells ====
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| <!-- more elaboration here, maybe fork off to another article? -->
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| In a 2000 article by Hanahan and Weinberg, the biological properties of malignant tumor cells were summarized as follows:<ref name="pmid10647931">{{cite journal |author=Hanahan D, Weinberg RA |title=The hallmarks of cancer |journal=Cell |volume=100 |issue=1 |pages=57–70 |year=2000 |pmid=10647931 |doi=}}</ref>
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| * Acquisition of self-sufficiency in [[growth factor|growth signals]], leading to unchecked growth.
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| * Loss of sensitivity to anti-growth signals, also leading to unchecked growth.
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| * Loss of capacity for [[apoptosis]], in order to allow growth despite genetic errors and external anti-growth signals.
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| * Loss of capacity for [[senescence]], leading to limitless replicative potential (immortality)
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| * Acquisition of sustained [[angiogenesis]], allowing the tumor to grow beyond the limitations of passive nutrient diffusion.
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| * Acquisition of ability to invade neighbouring [[biological tissue|tissues]], the defining property of invasive carcinoma.
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| * Acquisition of ability to build [[metastasis|metastases]] at distant sites, the classical property of malignant tumors (carcinomas or others).
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| The completion of these multiple steps would be a very rare event without :
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| * Loss of capacity to repair genetic errors, leading to an increased [[mutation]] rate (genomic instability), thus accelerating all the other changes.
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| These biological changes are classical in [[carcinoma]]s; other malignant tumor may not need all to achieve them all. For example, tissue invasion and displacement to distant sites are normal properties of [[leukocytes]]; these steps are not needed in the development of [[Leukemia]]. The different steps do not necessarily represent individual mutations. For example, inactivation of a single gene, coding for the [[P53]] protein, will cause genomic instability, evasion of apoptosis and increased angiogenesis.
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| == Prevention ==
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| Cancer prevention is defined as active measures to decrease the incidence of cancer. This can be accomplished by avoiding [[carcinogen]]s or altering their [[metabolism]], pursuing a lifestyle or diet that modifies cancer-causing factors and/or medical intervention ([[chemoprevention]], treatment of pre-malignant lesions). The [[epidemiology|epidemiological]] concept of "prevention" is usually defined as either [[primary prevention]], for people who have not been diagnosed with a particular disease, or [[secondary prevention]], aimed at reducing recurrence or complications of a previously diagnosed illness.
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| [[Observational study|Observational epidemiological studies]] that show associations between risk factors and specific cancers mostly serve to generate hypotheses about potential interventions that could reduce cancer incidence or [[morbidity]]. [[Randomized controlled trial]]s then test whether hypotheses generated by epidemiological trials and laboratory research actually result in reduced cancer incidence and mortality. In many cases, findings from observational [[epidemiological]] studies are not confirmed by randomized controlled trials.
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| About a third of the twelve most common cancers worldwide are due to nine potentially modifiable risk factors. Men with cancer are twice as likely as women to have a modifiable risk factor for their disease. The nine risk factors are [[tobacco smoking]], excessive [[alcoholic beverage|alcohol]] use, diet low in [[fruit]] and vegetables, limited [[physical exercise]], [[human papillomavirus]] infection (unsafe sex), urban [[air pollution]], domestic use of solid fuels, and contaminated injections (hepatitis B and C).<ref>{{cite journal |author=Danaei G, Vander Hoorn S, Lopez AD, Murray CJ, Ezzati M |title=Causes of cancer in the world: comparative risk assessment of nine behavioural and environmental risk factors |journal=Lancet |volume=366 |issue=9499 |pages=1784–93 |year=2005 |pmid=16298215 |doi=10.1016/S0140-6736(05)67725-2| url=http://www.thelancet.com/journals/lancet/article/PIIS0140673605677252/fulltext}}</ref>
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| ===Modifiable ("lifestyle") risk factors===
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| Examples of modifiable cancer risk factors include [[alcohol]] consumption (associated with increased risk of oral, esophageal, breast, and other cancers), smoking (although 20% of women with lung cancer have never smoked, versus 10% of men<ref>{{cite web | title= Lung Cancer in American Women: Facts | url=http://www.nationallungcancerpartnership.org/page.cfm?l=factsWomen | accessdate=2007-01-19 }}</ref>), physical inactivity (associated with increased risk of colon, breast, and possibly other cancers), and being [[obesity|overweight]] (associated with colon, breast, endometrial, and possibly other cancers). Based on epidemiologic evidence, it is now thought that avoiding excessive alcohol consumption may contribute to reductions in risk of certain cancers; however, compared with tobacco exposure, the magnitude of effect is modest or small and the strength of evidence is often weaker. Other lifestyle and environmental factors known to affect cancer risk (either beneficially or detrimentally) include certain sexually transmitted diseases, the use of exogenous hormones, exposure to [[ionizing radiation]] and [[ultraviolet]] radiation, and certain occupational and chemical exposures.
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| Every year, at least 200,000 people die worldwide from cancer related to their workplace. <ref name=WHO_occup>{{cite press release |title=WHO calls for prevention of cancer through healthy workplaces |publisher=World Health Organization |date=2007-04-27 |url=http://www.who.int/mediacentre/news/notes/2007/np19/en/index.html |accessdate=2007-10-13}} </ref> Millions of workers run the risk of developing cancers such as [[lung cancer]] and [[mesothelioma]] from inhaling asbestos fibers and tobacco smoke, or [[leukemia]] from exposure to [[benzene]] at their workplaces.<ref name=WHO_occup/> Currently, most cancer deaths caused by occupational risk factors occur in the developed world.<ref name=WHO_occup/> It is estimated that approximately 20,000 cancer deaths and 40,000 new cases of cancer each year in the U.S. are attributable to occupation.<ref>{{cite web|url=http://www.cdc.gov/niosh/topics/cancer/|title=National Institute for Occupational Safety and Health- Occupational Cancer |accessdate=2007-10-13|publisher=United States National Institute for Occupational Safety and Health}}</ref>
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| See [[alcohol and cancer]] for more on that topic.
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| ===Diet===
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| 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 [[Colorectal cancer|colon cancer]] is more common in the United States). Studies have shown that immigrants develop the risk of their new country, often within one generation, suggesting a substantial link between diet and cancer.<ref>{{cite journal |author=Buell P, Dunn JE |title=Cancer mortality among Japanese Issei and Nisei of California |journal=Cancer |volume=18 |issue= |pages=656-64 |year=1965 |pmid=14278899 |doi=}}</ref> Whether reducing obesity in a population also reduces cancer incidence is unknown.
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| 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.
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| Proposed dietary interventions for primary cancer risk reduction generally gain support from epidemiological association studies. Examples of such studies include reports that reduced meat consumption is associated with decreased risk of colon cancer,<ref name="pmid9663397">{{cite journal |author=Slattery ML, Boucher KM, Caan BJ, Potter JD, Ma KN |title=Eating patterns and risk of colon cancer |journal=Am. J. Epidemiol. |volume=148 |issue=1 |pages=4-16 |year=1998 |pmid=9663397 |doi=}}</ref>
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| and reports that consumption of coffee is associated with a reduced risk of liver cancer.<ref name="pmid17484871">{{cite journal |author=Larsson SC, Wolk A |title=Coffee consumption and risk of liver cancer: a meta-analysis |journal=Gastroenterology |volume=132 |issue=5 |pages=1740-5 |year=2007 |pmid=17484871 |doi=10.1053/j.gastro.2007.03.044}}</ref> Studies have linked consumption of grilled meat to an increased risk of [[stomach cancer]],<ref name="pmid9096659">{{cite journal |author=Ward MH, Sinha R, Heineman EF, ''et al'' |title=Risk of adenocarcinoma of the stomach and esophagus with meat cooking method and doneness preference |journal=Int. J. Cancer |volume=71 |issue=1 |pages=14-9 |year=1997 |pmid=9096659 |doi=}}</ref> [[Colorectal cancer|colon cancer]],<ref name="pmid16140978">{{cite journal |author=Sinha R, Peters U, Cross AJ, ''et al'' |title=Meat, meat cooking methods and preservation, and risk for colorectal adenoma |journal=Cancer Res. |volume=65 |issue=17 |pages=8034-41 |year=2005 |pmid=16140978 |doi=10.1158/0008-5472.CAN-04-3429}}</ref> [[breast cancer]],<ref name="pmid17435448">{{cite journal |author=Steck SE, Gaudet MM, Eng SM, ''et al'' |title=Cooked meat and risk of breast cancer--lifetime versus recent dietary intake |journal=Epidemiology (Cambridge, Mass.) |volume=18 |issue=3 |pages=373-82 |year=2007 |pmid=17435448 |doi=10.1097/01.ede.0000259968.11151.06}}</ref> and [[pancreatic cancer]],<ref name="pmid16172241">{{cite journal |author=Anderson KE, Kadlubar FF, Kulldorff M, ''et al'' |title=Dietary intake of heterocyclic amines and benzo(a)pyrene: associations with pancreatic cancer |journal=Cancer Epidemiol. Biomarkers Prev. |volume=14 |issue=9 |pages=2261-5 |year=2005 |pmid=16172241 |doi=10.1158/1055-9965.EPI-04-0514}}</ref> a phenomenon which could be due to the presence of carcinogens such as [[benzopyrene]] in foods cooked at high temperatures.
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| A 2005 [[secondary prevention]] study showed that consumption of a plant-based diet and lifestyle changes resulted in a reduction in cancer markers in a group of men with prostate cancer who were using no conventional treatments at the time.<ref name="Ornish">{{cite journal | author = Ornish D et al. | title = Intensive lifestyle changes may affect the progression of prostate cancer | journal = The Journal of Urology | volume = 174 | issue = 3 | pages = 1065-9; discussion 1069-70 | year = 2005 | id = PMID 16094059}}</ref>
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| These results were amplified by a 2006 study in which over 2,400 women were studied, half randomly assigned to a normal diet, the other half assigned to a diet containing less than 20% calories from fat. The women on the low fat diet were found to have a markedly lower risk of breast cancer recurrence, in the interim report of December, 2006.<ref>{{cite journal |author=Chlebowski RT, Blackburn GL, Thomson CA, ''et al'' |title=Dietary fat reduction and breast cancer outcome: interim efficacy results from the Women's Intervention Nutrition Study |journal=J. Natl. Cancer Inst. |volume=98 |issue=24 |pages=1767-76 |year=2006 |pmid=17179478 |doi=10.1093/jnci/djj494}}</ref>
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| ===Vitamins===
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| There is a concept that cancer can be prevented through vitamin supplementation stems from early observations correlating human disease with vitamin deficiency, such as [[pernicious anemia]] with [[vitamin B12]] deficiency, and [[scurvy]] with [[Vitamin C]] deficiency. This has largely not been proven to be the case with cancer, and vitamin supplementation is largely not proving effective in preventing cancer. The cancer-fighting components of food are also proving to be more numerous and varied than previously understood, so patients are increasingly being advised to consume fresh, unprocessed fruits and vegetables for maximal health benefits.<ref>The Omnivore's Dilemma, Andrew Pollan</ref>
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| The Canadian Cancer Society has advised Canadians that the intake of [[vitamin D]] has shown a reduction of cancers by close to 60%,<ref>{{cite web|url=http://www.cbc.ca/health/story/2007/06/07/vitamin-d-recommendations.html|title=Take vitamin D to reduce cancer risk, Canadian Cancer Society advises|accessdate=2007-07-27}}</ref> and at least one study has shown a specific benefit for this vitamin in preventing colon cancer.<ref>{{cite web|url=http://www.cancer.org/docroot/NWS/content/NWS_1_1x_Vitamin_D_Has_Role_in_Colon_Cancer_Prevention.asp|title=Vitamin D Has Role in Colon Cancer Prevention|accessdate=2007-07-27}}</ref>
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| Vitamin D and its protective effect against cancer has been contrasted with the risk of malignancy from sun exposure. Since exposure to the sun enhances natural human production of vitamin D, some cancer researchers have argued that the potential deleterious malignant effects of sun exposure are far outweighed by the cancer-preventing effects of extra vitamin D synthesis in sun-exposed skin. In 2002, Dr. William B. Grant claimed that 23,800 premature cancer deaths occur in the US annually due to insufficient UVB exposure (apparently via vitamin D deficiency).<ref>{{cite web|url=http://www3.interscience.wiley.com/cgi-bin/abstract/91016211/ABSTRACT?CRETRY=1&SRETRY=0|title=www3.interscience.wiley.com/cgi-bin/abstract/91016211/ABSTRACT?CRETRY=1&SRETRY=0<!--INSERT TITLE-->|accessdate=2007-07-27}}</ref> This is higher than 8,800 deaths occurred from melanoma or squamous cell carcinoma, so the overall effect of sun exposure might be beneficial. Another research group<ref>{{cite web|url=http://cat.inist.fr/?aModele=afficheN&cpsidt=17357586|title=cat.inist.fr/?aModele=afficheN&cpsidt=17357586<!--INSERT TITLE-->|accessdate=2007-07-27}}</ref><ref>
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| Grant WB, Garland CF, Holick MF. Comparisons of estimated economic burdens due to insufficient solar ultraviolet irradiance and vitamin D and excess solar UV irradiance for the United States. Photochem Photobiol. 2005 Nov-Dec;81(6):1276-86.</ref> estimates that 50,000–63,000 individuals in the United States and 19,000 - 25,000 in the UK die prematurely from cancer annually due to insufficient vitamin D.
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| The case of [[beta-carotene]] provides an example of the importance of [[clinical trial|randomized clinical trials]]. [[Epidemiology|Epidemiologists]] studying both diet and serum levels observed that high levels of [[beta-carotene]], a precursor to [[vitamin A]], were associated with a protective effect, reducing the risk of cancer. This effect was particularly strong in [[lung cancer]]. This [[hypothesis]] led to a series of large randomized [[clinical trials]] conducted in both Finland and the [[United States]] (CARET study) during the 1980s and 1990s. This study provided about 80,000 smokers or former smokers with daily supplements of beta-carotene or [[placebo]]s. 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.<ref name="CancerTopics-Bcarotene">National Cancer Institute [http://www.cancer.gov/cancertopics/factsheet/Prevention/betacarotene Questions and Answers About Beta Carotene Chemoprevention Trials] U.S. National Institutes of Health</ref>
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| Results reported in the [[Journal of the American Medical Association]] (JAMA) in 2007 indicate that folic acid supplementation is not effective in preventing colon cancer, and folate consumers may be more likely to form colon polyps.<ref>{{cite journal |author=Cole BF, Baron JA, Sandler RS, ''et al'' |title=Folic acid for the prevention of colorectal adenomas: a randomized clinical trial |journal=JAMA |volume=297 |issue=21 |pages=2351-9 |year=2007 |pmid=17551129 |doi=10.1001/jama.297.21.2351}}</ref>
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| ===Chemoprevention===
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| The concept that medications could be used to prevent cancer is an attractive one, and many high-quality clinical trials support the use of such chemoprevention in defined circumstances.
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| Daily use of [[tamoxifen]], a [[selective estrogen receptor modulator]] (SERM), typically for 5 years, has been demonstrated to reduce the risk of developing [[breast cancer]] in high-risk women by about 50%. A recent study reported that the [[selective estrogen receptor modulator]] [[raloxifene]] has similar benefits to [[tamoxifen]] in preventing breast cancer in high-risk women, with a more favorable side effect profile.<ref name=STAR-P2>{{cite journal |author=Vogel V, Costantino J, Wickerham D, Cronin W, Cecchini R, Atkins J, Bevers T, Fehrenbacher L, Pajon E, Wade J, Robidoux A, Margolese R, James J, Lippman S, Runowicz C, Ganz P, Reis S, McCaskill-Stevens W, Ford L, Jordan V, Wolmark N |title=Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial |journal=JAMA |volume=295 |issue=23 |pages=2727-41 |year=2006 |pmid=16754727}}</ref>
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| [[Raloxifene]] is a SERM like [[tamoxifen]]; it has been shown (in the STAR trial) to reduce the risk of breast cancer in high-risk women equally as well as tamoxifen. In this trial, which studied almost 20,000 women, [[raloxifene]] had fewer side effects than [[tamoxifen]], though it did permit more [[Ductal carcinoma|DCIS]] to form.<ref name=STAR-P2/>
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| [[Finasteride]], a [[5-alpha-reductase inhibitor]], has been shown to lower the risk of prostate cancer, though it seems to mostly prevent low-grade tumors.<ref>{{cite journal |author=Thompson I, Goodman P, Tangen C, Lucia M, Miller G, Ford L, Lieber M, Cespedes R, Atkins J, Lippman S, Carlin S, Ryan A, Szczepanek C, Crowley J, Coltman C |title=The influence of finasteride on the development of prostate cancer |journal=N Engl J Med |volume=349 |issue=3 |pages=215-24 |year=2003 |pmid=12824459}}</ref>
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| The effect of [[COX-2 selective inhibitor|COX-2 inhibitors]] such as [[rofecoxib]] and [[celecoxib]] upon the risk of colon polyps have been studied in [[familial adenomatous polyposis]] patients<ref>{{cite journal |author=Hallak A, Alon-Baron L, Shamir R, Moshkowitz M, Bulvik B, Brazowski E, Halpern Z, Arber N |title=Rofecoxib reduces polyp recurrence in familial polyposis |journal=Dig Dis Sci |volume=48 |issue=10 |pages=1998-2002 |year=2003 |pmid=14627347}}</ref>
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| and in the general population.<ref>{{cite journal |author=Baron J, Sandler R, Bresalier R, Quan H, Riddell R, Lanas A, Bolognese J, Oxenius B, Horgan K, Loftus S, Morton D |title=A randomized trial of rofecoxib for the chemoprevention of colorectal adenomas |journal=Gastroenterology |volume=131 |issue=6 |pages=1674-82 |year=2006 |pmid=17087947}}</ref><ref>{{cite journal |author=Bertagnolli M, Eagle C, Zauber A, Redston M, Solomon S, Kim K, Tang J, Rosenstein R, Wittes J, Corle D, Hess T, Woloj G, Boisserie F, Anderson W, Viner J, Bagheri D, Burn J, Chung D, Dewar T, Foley T, Hoffman N, Macrae F, Pruitt R, Saltzman J, Salzberg B, Sylwestrowicz T, Gordon G, Hawk E |title=Celecoxib for the prevention of sporadic colorectal adenomas |journal=N Engl J Med |volume=355 |issue=9 |pages=873-84 |year=2006 |pmid=16943400}}</ref>
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| In both groups, there were significant reductions in [[colon polyp]] [[incidence (epidemiology)|incidence]], but this came at the price of increased cardiovascular toxicity.
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| ===Genetic testing===
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| [[Genetic testing]] for high-risk individuals is already available for certain cancer-related genetic mutations. Carriers of genetic mutations that increase risk for cancer incidence can undergo enhanced surveillance, chemoprevention, or risk-reducing surgery. Early identification of inherited genetic risk for cancer, along with cancer-preventing interventions such as surgery or enhanced surveillance, can be lifesaving for high-risk individuals.
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| {| class="wikitable"
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| |-
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| ! Gene
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| ! Cancer types
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| ! Availability
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| |-
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| | [[BRCA1]], [[BRCA2]]
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| | Breast, ovarian, pancreatic
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| | Commercially available for clinical specimens
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| |-
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| | [[MLH1]], [[MSH2]], [[MSH6]], PMS1, PMS2
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| | Colon, uterine, small bowel, stomach, urinary tract
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| | Commercially available for clinical specimens
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| |}
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| ===Vaccination===
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| Considerable research effort is now devoted to the development of [[vaccine]]s to prevent infection by oncogenic infectious agents, as well as to mount an immune response against cancer-specific [[epitope]]s) and to potential venues for [[gene therapy]] for individuals with genetic mutations or polymorphisms that put them at high risk of cancer.
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| As reported above, a preventive [[human papillomavirus vaccine]] exists that targets certain sexually transmitted strains of [[human papillomavirus]] that are associated with the development of [[cervical cancer]] and [[genital warts]]. The only two HPV vaccines on the market as of October 2007 are [[Gardasil]] and [[Cervarix]].
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| ===Screening===
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| Cancer [[Screening (medicine)|screening]] is an attempt to detect unsuspected cancers in an asymptomatic population. Screening tests suitable for large numbers of healthy people must be relatively affordable, safe, noninvasive procedures with acceptably low rates of [[Type I and type II errors|false positive]] results. If signs of cancer are detected, more definitive and invasive follow up tests are performed to confirm the diagnosis.
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| Screening for cancer can lead to earlier diagnosis in specific cases. Early diagnosis may lead to extended life, but may also falsely prolong the lead time to death through [[lead time bias]] or [[length time bias]].
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| A number of different screening tests have been developed for different malignancies. Breast cancer screening can be done by [[breast self-examination]], though this approach was discredited by a 2005 study in over 300,000 Chinese women. Screening for breast cancer with [[mammogram]]s has been shown to reduce the average stage of diagnosis of breast cancer in a population. Stage of diagnosis in a country has been shown to decrease within ten years of introduction of mammographic screening programs. Colorectal cancer can be detected through [[fecal occult blood test]]ing and [[colonoscopy]], which reduces both colon cancer incidence and mortality, presumably through the detection and removal of pre-malignant polyps. Similarly, cervical cytology testing (using the [[Pap smear]]) leads to the identification and excision of precancerous lesions. Over time, such testing has been followed by a dramatic reduction of [[cervical cancer]] incidence and mortality. [[Testicular self-examination]] is recommended for men beginning at the age of 15 years to detect [[testicular cancer]]. Prostate cancer can be screened using a [[digital rectal exam]] along with [[prostate specific antigen]] (PSA) blood testing, though some authorities (such as the US Preventive Services Task Force) recommend against routinely screening all men.
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| 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 [[Prostate specific antigen|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 [[Urinary incontinence|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.
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| Cervical cancer screening via the [[Pap smear]] has the best cost-benefit profile of all the forms of cancer screening from a public health perspective as, being largely caused by a virus, it has clear risk factors (sexual contact), and the natural progression of cervical cancer is that it normally spreads slowly over a number of years therefore giving more time for the screening program to catch it early. Moreover, the test itself is easy to perform and relatively cheap.
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| 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.
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| Use of [[medical imaging]] to search for cancer in people without clear symptoms is similarly marred with problems. There is a significant risk of detection of what has been recently called an ''[[incidentaloma]]'' - a benign lesion that may be interpreted as a malignancy and be subjected to potentially dangerous investigations. Recent studies of [[CT scan]]-based screening for [[lung cancer]] in smokers have had equivocal results, and systematic screening is not recommended as of July 2007. [[Randomized clinical trials]] of plain-film [[chest X-rays]] to screen for lung cancer in smokers have shown no benefit for this approach.
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| [[Canine cancer detection]] has shown promise, but is still in the early stages of research.
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| == Epidemiology ==
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| [[Image:Cancer rate.gif|thumb|right|The risk of cancer rises with age]]
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| 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.
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| 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" followed in 1956 (otherwise known as the British doctors study). Richard Doll left the London Medical Research Center (MRC), to start the Oxford unit for Cancer epidemiology in 1968. With the use of computers, the unit was the first to compile large amounts of cancer data. Modern epidemiological methods are closely linked to current concepts of disease and [[public health]] policy. Over the past 50 years, great efforts have been spent on gathering data across medical practise, hospital, provincial, state, and even country boundaries, as a way to study the interdependence of environmental and cultural factors on cancer incidence.
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| Cancer epidemiology must contend with problems of [[lead time bias]] and length time bias. Lead time bias is the concept that early diagnosis may artificially inflate the survival statistics of a cancer, without really improving the natural history of the disease. Length bias is the concept that slower growing, more indolent tumors are more likely to be diagnosed by screening tests, but improvements in diagnosing more cases of indolent cancer may not translate into better patient outcomes after the implementation of screening programs. A similar epidemiological concern is [[overdiagnosis]], the tendency of screening tests to diagnose diseases that may not actually impact the patient's longevity. This problem especially applies to [[prostate cancer]] and PSA screening.<ref name="pmid15283896">{{cite journal |author=Brawley OW |title=Prostate cancer screening: clinical applications and challenges |journal=Urol. Oncol. |volume=22 |issue=4 |pages=353–7 |year=2004 |pmid=15283896 |doi=10.1016/j.urolonc.2004.04.014}}</ref>
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| Some cancer researchers have argued that negative cancer clinical trials lack sufficient [[statistical power]] to discover a benefit to treatment. This may be due to fewer patients enrolled in the study than originally planned.<ref name="pmid17687153">{{cite journal |author=Bedard PL, Krzyzanowska MK, Pintilie M, Tannock IF |title=Statistical power of negative randomized controlled trials presented at American Society for Clinical Oncology annual meetings |journal=J. Clin. Oncol. |volume=25 |issue=23 |pages=3482–7 |year=2007 |pmid=17687153 |doi=10.1200/JCO.2007.11.3670}}</ref>
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| State and regional [[cancer registry|cancer registries]] are organizations that abstract clinical data about cancer from patient medical records. These institutions provide information to state and national public health groups to help track trends in cancer diagnosis and treatment. One of the largest and most important [[cancer registry|cancer registries]] is SEER, administered by the US Federal government.<ref>{{cite web |url=http://seer.cancer.gov/ |title=SEER Surveillance Epidemiology and End Results |accessdate=2007-11-02 |format= |work=}}</ref> Health information privacy concerns have led to the restricted use of [[cancer registry]] data in the United States Department of Veterans Affairs <ref name="lancetva">Furlow, B, [http://www.thelancet.com/journals/lanonc/article/PIIS1470204507702589/fulltext Accuracy of US cancer surveillance under threat] ''Lancet Oncology'' 2007; 8:762-763. Retrieved [[2007-11-01]].</ref><ref name= "mpva">[http://www.medpagetoday.com/InfectiousDisease/PublicHealth/tb/6563 VA Cancer Data Blockade May Imperil Surveillance] ([[31 August]] [[2007]]). ''Medpage Today''. Retrieved [[2007-11-01]]. </ref><ref name="nytva">[http://www.nytimes.com/2007/10/10/health/10cancer.html States and V.A. at Odds on Cancer Data] ([[10 October]] [[2007]]). ''New York Times''. Retrieved [[2007-11-01]].</ref> and other institutions.<ref name="iomhip">[http://www.iom.edu/Object.File/Master/43/927/HIPAA%20IOM%20meeting%20607r.Howe.pdf Negative Impact of HIPAA on Population-Based Cancer Registry Research: Update of a Brief Survey] (14 June 2007). ''IOM Presentation''. Retrieved [[2007-11-01]].</ref>
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| In some Western countries, such as the USA,<ref name="CACancerJClin2005-Jemal" /> and the UK<ref name="BBC2000-news">
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| [http://news.bbc.co.uk/1/hi/health/1015657.stm Cancer: Number one killer] (9 November 2000). ''BBC News online''. Retrieved [[2005-01-29]].</ref> 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 [[epidemiology|epidemiological]] terminology.
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| Cancer epidemiology closely mirrors risk factor spread in various countries. [[Hepatocellular carcinoma]] ([[liver]] cancer) is rare in the West but is the main cancer in China and neighbouring countries, most likely due to the [[endemic (epidemiology)|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.
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| == History ==
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| [[Image:Breast cancer gross appearance.jpg|thumb|150px|right|Typical macroscopic (gross) appearance of cancer. This invasive [[ductal carcinoma]] of the breast (pale area at the center) shows an oval tumor surrounded by spikes of whitish scar tissue in the surrounding yellow fatty tissue. The silhouette vaguely resembles a crab.]]
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| Today, the Greek term [[carcinoma]] is the medical term for a malignant tumor derived from [[epithelium|epithelial]] cells. It is [[Aulus Cornelius Celsus|Celsus]] who translated ''carcinos'' into the [[Latin]] ''cancer'', also meaning crab.
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| [[Galen]] used "''oncos''" to describe ''all'' tumours, the root for the modern word [[oncology]].<ref name="Galen">{{cite journal |author=Karpozilos A, Pavlidis N |title=The treatment of cancer in Greek antiquity |journal=Eur. J. Cancer |volume=40 |issue=14 |pages=2033–40 |year=2004 |pmid=15341975 |doi=10.1016/j.ejca.2004.04.036}}</ref>
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| [[Hippocrates]] described several kinds of cancers. He called benign tumours ''oncos'', [[Greek language|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 center surrounded by pointy projections, vaguely resembling the shape of a crab (see picture). He later added the suffix ''-oma'', Greek for swelling, giving the name ''carcinoma''. Since it was against Greek tradition to open the body, Hippocrates only described and made drawings of outwardly visible tumors on the skin, nose, and breasts. Treatment was based on the [[humor theory]] of four bodily fluids (black and yellow bile, blood, and phlegm). According to the patient's humor, treatment consisted of diet, blood-letting, and/or laxatives. Through the centuries it was discovered that cancer could occur anywhere in the body, but humor-theory based treatment remained popular until the 19th century with the discovery of [[cell (biology)|cells]].
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| The first known [[Surgery|surgical]] treatment for cancer was described in the 1020s by [[Avicenna]] (Ibn Sina) in ''The Canon of Medicine''. He stated that the [[excision]] should be radical and that all diseased [[tissue]] should be removed, which included the use of [[amputation]] or the removal of [[vein]]s running in the direction of the [[tumor]]. He also recommended the use of [[cauterization]] for the area being treated if necessary.<ref name=Patricia>Patricia Skinner (2001), [http://findarticles.com/p/articles/mi_g2603/is_0007/ai_2603000716 Unani-tibbi], ''Encyclopedia of Alternative Medicine''</ref>
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| In the 16th and 17th centuries, it became more acceptable for doctors to [[autopsy|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 [[infectious disease|contagious]].<ref name="Marilyn Yalom">
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| Marilyn Yalom "A history of the breast" 1997. New York: Alfred A. Knopf. ISBN 0-679-43459-3</ref>
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| With the widespread use of the microscope in the 18th century, it was discovered that the 'cancer poison' spread from the primary tumor through the lymph nodes to other sites ("[[metastasis]]"). This view of the disease was first formulated by the English surgeon [[Campbell De Morgan]] between 1871 and 1874.<ref>{{cite journal |author=Grange JM, Stanford JL, Stanford CA |title=Campbell De Morgan's 'Observations on cancer', and their relevance today |journal=Journal of the Royal Society of Medicine |volume=95 |issue=6 |pages=296-9 |year=2002 |url=http://www.jrsm.org/cgi/content/full/95/6/296|pmid=12042378 |doi=}}</ref> The use of [[surgery]] to treat cancer had poor results due to problems with hygiene. The renowned Scottish surgeon Alexander Monro saw only 2 breast tumor patients out of 60 surviving surgery for two years. In the 19th century, [[asepsis]] improved surgical hygiene and as the survival statistics went up, surgical removal of the tumor became the primary treatment for cancer. With the exception of [[William Coley]] who in the late 1800s felt that the rate of cure after surgery had been higher ''before'' asepsis (and who injected bacteria into tumors with mixed results), cancer treatment became dependent on the individual art of the surgeon at removing a tumor. During the same period, the idea that the body was made up of various [[tissue (biology)|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.
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| 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.
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| 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.
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| ==Research==
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| {{main|Cancer research}}
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| Cancer research is the intense scientific effort to understand disease processes and discover possible therapies. The improved understanding of [[molecular biology]] and [[cellular biology]] due to cancer research has led to a number of new, effective treatments for cancer since President Nixon declared "War on Cancer" in 1971.
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| ==See also==
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| * [[American Cancer Society]] | | * [[American Cancer Society]] |
| * [[National Cancer Institute]] | | * [[National Cancer Institute]] |
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| * [[List of cancer types]] | | * [[List of cancer types]] |
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| ==References==
| | ==External Links== |
| {{reflist|2}}
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| ===General references===
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| * ''The Basic Science of Oncology.'' Tannock IF, Hill RP ''et al'' (eds) 4th ed.2005 McGraw-Hill. ISBN 0-07138-774-9.
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| * ''Principles of Cancer Biology.'' Kleinsmith, LJ (2006). Pearson Benjamin Cummings. ISBN 0-80534-003-3.
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| * {{cite journal | author = Parkin D, Bray F, Ferlay J, Pisani P | title = Global cancer statistics, 2002. | journal = CA Cancer J Clin | volume = 55 | issue = 2 | pages = 74-108 | year = | id = PMID}}''[http://caonline.amcancersoc.org/cgi/content/full/55/2/74 Full text]''
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| * ''Food, Nutrition, Physical Activity, and the Prevention of Cancer: a Global Perspective''. World Cancer Research Fund (2007). ISBN 978-0-9722522-2-5. ''[http://www.wcrf-uk.org/research_science/expert_report.lasso Full text]''
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| ==External links== | |
| * {{dmoz|Health/Conditions_and_Diseases/Cancer/}} | | * {{dmoz|Health/Conditions_and_Diseases/Cancer/}} |
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| ===Professional and research=== | | ===Professional and Research=== |
| ;Global | | ;Global |
| * [http://www.who.int/cancer/en/ The World Health Organization's cancer site] A review of worldwide strategies for the prevention and treatment of cancer. | | * [http://www.who.int/cancer/en/ The World Health Organization's cancer site] A review of worldwide strategies for the prevention and treatment of cancer. |
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| * [http://www.icr.ac.uk The Institute of Cancer Research] One of the world's foremost independent cancer research organisations, based in the United Kingdom. | | * [http://www.icr.ac.uk The Institute of Cancer Research] One of the world's foremost independent cancer research organisations, based in the United Kingdom. |
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| ===Support and advocacy=== | | ===Support and Advocacy=== |
| * [http://www.americancancersociety.org American Cancer Society] Patient advocate group | | * [http://www.americancancersociety.org American Cancer Society] Patient advocate group |
| * [http://www.aacr.org/home/survivors--advocates.aspx American Association for Cancer Research Survivor and Patient Advocacy] | | * [http://www.aacr.org/home/survivors--advocates.aspx American Association for Cancer Research Survivor and Patient Advocacy] |
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| {{WikiDoc Sources}} | | {{WikiDoc Sources}} |
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| | [[Category:Aging-associated diseases]] |
| | [[Category:Causes of death]] |
| | [[Category:Oncology|*]] |
| | [[Category:Pathology]] |
| | [[Category:Types of cancer]] |
| | [[Category:Occupational safety and health]] |
| | [[Category:Hematology]] |
