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  • Section: Medicine /Sunday 12th October 2014

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    * Cancer *

    سرطان ، چَنگار


    Iranian_Flag_Hand_Love_Heart.jpg
    (Wikipedia) - Cancer For other uses, see Cancer (disambiguation). Cancer ICD-10 ICD-9 DiseasesDB MedlinePlus MeSH
    Classification and external resources
    A coronal CT scan showing a malignant mesothelioma Legend: → tumor ←, ✱ central pleural effusion, 1 & 3 lungs, 2 spine, 4 ribs, 5 aorta, 6 spleen, 7 & 8 kidneys, 9 liver.
    C00—C97
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    Cancer i/ˈkænsər/, also known as a malignant tumor, is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. Not all tumors are cancerous; benign tumors do not spread to other parts of the body. Possible signs and symptoms include: a new lump, abnormal bleeding, a prolonged cough, unexplained weight loss, and a change in bowel movements, among others. While these symptoms may indicate cancer they may also occur due to other issues. There are over 100 different known cancers that affect humans.

    Tobacco use is the cause of about 22% of cancer deaths. Another 10% is due to obesity, a poor diet, lack of physical activity, and drinking alcohol. Other factors include certain infections, exposure to ionizing radiation, and environmental pollutants. In the developing world nearly 20% of cancers are due to infections such as hepatitis B, hepatitis C, and human papillomavirus. These factors act, at least partly, by changing the genes of a cell. Typically many such genetic changes are required before cancer develops. Approximately 5–10% of cancers are due to genetic defects inherited from a person''s parents. Cancer can be detected by certain signs and symptoms or screening tests. It is then typically further investigated by medical imaging and confirmed by biopsy.

    Many cancers can be prevented by not smoking, eating more vegetables, fruits and whole grains, eating less meat and refined carbohydrates, maintaining a healthy weight, exercising, minimizing sunlight exposure, and being vaccinated against certain infectious diseases. Early detection through screening is useful for cervical and colorectal cancer. The benefits of screening in breast cancer are controversial. Cancer is often treated with some combination of radiation therapy, surgery, chemotherapy, and targeted therapy. Pain and symptom management are an important part of care. Palliative care is particularly important in those with advanced disease. The chance of survival depends on the type of cancer and extent of disease at the start of treatment. In children under 15 at diagnosis the five year survival rate in the developed world is on average 80%. For cancer in the United States the average five year survival rate is 66%.

    In 2012 about 14.1 million new cases of cancer occurred globally. It caused about 8.2 million deaths or 14.6% of all human deaths. The most common types of cancer in males are lung cancer, prostate cancer, colorectal cancer, and stomach cancer, and in females, the most common types are breast cancer, colorectal cancer, lung cancer, and cervical cancer. Skin cancer is not included in these statistics and if it were it would account for at least 40% of cases. In children acute lymphoblastic leukaemia and brain tumors are most common except in Africa where non-Hodgkin lymphoma occurs more often. In 2012 about 165,000 children less than 15 years of age were diagnosed with cancer. The risk of cancer increases significantly with age and many cancers occur more commonly in developed countries. Rates are increasing as more people live to an old age and as lifestyle changes occur in the developing world. The financial costs of cancer have been estimated at $1.16 trillion US dollars per year as of 2010.

    Contents

    Definitions

    Cancers are a large family of diseases which involve abnormal cell growth with the potential to invade or spread to other parts of the body. They form a subset of neoplasms. A neoplasm or tumor is a group of cells that have undergone unregulated growth, and will often form a mass or lump, but may be distributed diffusely.

    Six characteristics of cancer have been proposed:

    The progression from normal cells to cells that can form a discernible mass to outright cancer involves multiple steps known as malignant progression.

    Signs and symptoms Main article: Cancer signs and symptomsSymptoms of cancer metastasis depend on the location of the tumor.

    When cancer begins, it invariably produces no symptoms. Signs and symptoms only appear as the mass continues to grow or ulcerates. The findings that result depend on the type and location of the cancer. Few symptoms are specific, with many of them also frequently occurring in individuals who have other conditions. Cancer is the new "great imitator". Thus it is not uncommon for people diagnosed with cancer to have been treated for other diseases which were assumed to be causing their symptoms.

    Local effects

    Local symptoms may occur due to the mass of the tumor or its ulceration. For example, mass effects from lung cancer can cause blockage of the bronchus resulting in cough or pneumonia; esophageal cancer can cause narrowing of the esophagus, making it difficult or painful to swallow; and colorectal cancer may lead to narrowing or blockages in the bowel, resulting in changes in bowel habits. Masses in breasts or testicles may be easily felt. Ulceration can cause bleeding which, if it occurs in the lung, will lead to coughing up blood, in the bowels to anemia or rectal bleeding, in the bladder to blood in the urine, and in the uterus to vaginal bleeding. Although localized pain may occur in advanced cancer, the initial swelling is usually painless. Some cancers can cause buildup of fluid within the chest or abdomen.

    Systemic symptoms

    General symptoms occur due to distant effects of the cancer that are not related to direct or metastatic spread. These may include: unintentional weight loss, fever, being excessively tired, and changes to the skin. Hodgkin disease, leukemias, and cancers of the liver or kidney can cause a persistent fever of unknown origin.

    Some cancers may cause specific groups of systemic symptoms, termed paraneoplastic phenomena. Examples include the appearance of myasthenia gravis in thymoma and clubbing in lung cancer.

    Metastasis Main article: Metastasis

    Cancer can spread from its original site by local spread, lymphatic spread to regional lymph nodes or by blood (haematogenous spread) to distant sites, known as metastasis. When cancer spreads by haematogenous route, it usually spreads all over body. However, cancer ''seeds'' grow in certain selected site only (''soil'') as hypothesized in soil and seed hypothesis of cancer metastasis. The symptoms of metastatic cancers depend on the location of the tumor, and can include enlarged lymph nodes (which can be felt or sometimes seen under the skin and are typically hard), enlarged liver or enlarged spleen, which can be felt in the abdomen, pain or fracture of affected bones, and neurological symptoms.

    Causes Main article: Causes of cancer

    The great majority of cancers, some 90–95% of cases, are due to environmental factors. The remaining 5–10% are due to inherited genetics. Environmental, as used by cancer researchers, means any cause that is not inherited genetically, such as lifestyle, economic and behavioral factors, and not merely pollution. Common environmental factors that contribute to cancer death include tobacco (25–30%), diet and obesity (30–35%), infections (15–20%), radiation (both ionizing and non-ionizing, up to 10%), stress, lack of physical activity, and environmental pollutants.

    It is nearly impossible to prove what caused a cancer in any individual, because most cancers have multiple possible causes. For example, if a person who uses tobacco heavily develops lung cancer, then it was probably caused by the tobacco use, but since everyone has a small chance of developing lung cancer as a result of air pollution or radiation, then there is a small chance that the cancer developed because of air pollution or radiation. Excepting the rare transmissions that occur with pregnancies and only a marginal few organ donors, cancer is generally not a transmissible disease.

    Chemicals Further information: Alcohol and cancer and Smoking and cancerThe incidence of lung cancer is highly correlated with smoking.

    Exposure to particular substances have been linked to specific types of cancer. These substances are called carcinogens.

    Tobacco smoking causes 90% of lung cancer. It also causes cancer in the larynx, head, neck, stomach, bladder, kidney, esophagus and pancreas. Tobacco smoke contains over fifty known carcinogens, including nitrosamines and polycyclic aromatic hydrocarbons. Tobacco is responsible for about one in three of all cancer deaths in the developed world, and about one in five worldwide. Lung cancer death rates in the United States have mirrored smoking patterns, with increases in smoking followed by dramatic increases in lung cancer death rates and, more recently, decreases in smoking rates since the 1950s followed by decreases in lung cancer death rates in men since 1990.

    In Western Europe 10% of cancers in males and 3% of all cancers in females are attributed to alcohol exposure, especially cancer of the liver and of the digestive tract.

    Cancer related to substance exposures at work is believed to represent between 2–20% of all cases. Every year, at least 200,000 people die worldwide from cancer related to their workplaces. Millions of workers run the risk of developing cancers such as lung cancer and mesothelioma from inhaling tobacco smoke or asbestos fibers on the job, or leukemia from exposure to benzene at their workplaces.

    Diet and exercise Main article: Diet and cancer

    Diet, physical inactivity, and obesity are related to up to 30–35% of cancer deaths. In the United States excess body weight is associated with the development of many types of cancer and is a factor in 14–20% of all cancer deaths. Correspondingly, a UK study including data on over 5 million people showed higher body mass index to be related to at least 10 types of cancer, and responsible for around 12,000 cases each year in that country. Physical inactivity is believed to contribute to cancer risk not only through its effect on body weight but also through negative effects on immune system and endocrine system. More than half of the effect from diet is due to overnutrition (eating too much), rather than from eating too few vegetables or other healthful foods.

    Some specific foods are linked to specific cancers. A high-salt diet is linked to gastric cancer. aflatoxin B1, a frequent food contaminate, causes liver cancer. Betel nut chewing causes oral cancer. The differences in dietary practices may partly explain differences in cancer incidence in different countries. For example, gastric cancer is more common in Japan due to its high-salt diet and colon cancer is more common in the United States. Immigrants develop the risk of their new country, often within one generation, suggesting a substantial link between diet and cancer.

    Infection Main article: Infectious causes of cancer

    Worldwide approximately 18% of cancer deaths are related to infectious diseases. This proportion varies in different regions of the world from a high of 25% in Africa to less than 10% in the developed world. Viruses are the usual infectious agents that cause cancer but bacteria and parasites may also have an effect.

    A virus that can cause cancer is called an oncovirus. These include human papillomavirus (cervical carcinoma), Epstein–Barr virus (B-cell lymphoproliferative disease and nasopharyngeal carcinoma), Kaposi''s sarcoma herpesvirus (Kaposi''s sarcoma and primary effusion lymphomas), hepatitis B and hepatitis C viruses (hepatocellular carcinoma), and Human T-cell leukemia virus-1 (T-cell leukemias). Bacterial infection may also increase the risk of cancer, as seen in Helicobacter pylori-induced gastric carcinoma. Parasitic infections strongly associated with cancer include Schistosoma haematobium (squamous cell carcinoma of the bladder) and the liver flukes, Opisthorchis viverrini and Clonorchis sinensis (cholangiocarcinoma).

    Radiation Main article: Radiation-induced cancer

    Up to 10% of invasive cancers are related to radiation exposure, including both ionizing radiation and non-ionizing ultraviolet radiation. Additionally, the vast majority of non-invasive cancers are non-melanoma skin cancers caused by non-ionizing ultraviolet radiation, mostly from sunlight. Sources of ionizing radiation include medical imaging and radon gas.

    Ionizing radiation is not a particularly strong mutagen. Residential exposure to radon gas, for example, has similar cancer risks as passive smoking. Radiation is a more potent source of cancer when it is combined with other cancer-causing agents, such as radon gas exposure plus smoking tobacco. Radiation can cause cancer in most parts of the body, in all animals, and at any age. Children and adolescents are twice as likely to develop radiation-induced leukemia as adults; radiation exposure before birth has ten times the effect.

    Medical use of ionizing radiation is a small but growing source of radiation-induced cancers. Ionizing radiation may be used to treat other cancers, but this may, in some cases, induce a second form of cancer. It is also used in some kinds of medical imaging.

    Prolonged exposure to ultraviolet radiation from the sun can lead to melanoma and other skin malignancies. Clear evidence establishes ultraviolet radiation, especially the non-ionizing medium wave UVB, as the cause of most non-melanoma skin cancers, which are the most common forms of cancer in the world.

    Non-ionizing radio frequency radiation from mobile phones, electric power transmission, and other similar sources have been described as a possible carcinogen by the World Health Organization''s International Agency for Research on Cancer. However, studies have not found a consistent link between cell phone radiation and cancer risk.

    Heredity Main article: Cancer syndrome

    The vast majority of cancers are non-hereditary ("sporadic cancers"). Hereditary cancers are primarily caused by an inherited genetic defect. Less than 0.3% of the population are carriers of a genetic mutation which has a large effect on cancer risk and these cause less than 3–10% of all cancer. Some of these syndromes include: certain inherited mutations in the genes BRCA1 and BRCA2 with a more than 75% risk of breast cancer and ovarian cancer, and hereditary nonpolyposis colorectal cancer (HNPCC or Lynch syndrome) which is present in about 3% of people with colorectal cancer, among others.

    Physical agents

    Some substances cause cancer primarily through their physical, rather than chemical, effects on cells. A prominent example of this is prolonged exposure to asbestos, naturally occurring mineral fibers which are a major cause of mesothelioma, which is a cancer of the serous membrane, usually the serous membrane surrounding the lungs. Other substances in this category, including both naturally occurring and synthetic asbestos-like fibers such as wollastonite, attapulgite, glass wool, and rock wool, are believed to have similar effects. Non-fibrous particulate materials that cause cancer include powdered metallic cobalt and nickel, and crystalline silica (quartz, cristobalite, and tridymite). Usually, physical carcinogens must get inside the body (such as through inhaling tiny pieces) and require years of exposure to develop cancer.

    Physical trauma resulting in cancer is relatively rare. Claims that breaking bones resulted in bone cancer, for example, have never been proven. Similarly, physical trauma is not accepted as a cause for cervical cancer, breast cancer, or brain cancer. One accepted source is frequent, long-term application of hot objects to the body. It is possible that repeated burns on the same part of the body, such as those produced by kanger and kairo heaters (charcoal hand warmers), may produce skin cancer, especially if carcinogenic chemicals are also present. Frequently drinking scalding hot tea may produce esophageal cancer. Generally, it is believed that the cancer arises, or a pre-existing cancer is encouraged, during the process of repairing the trauma, rather than the cancer being caused directly by the trauma. However, repeated injuries to the same tissues might promote excessive cell proliferation, which could then increase the odds of a cancerous mutation. There is no evidence that inflammation itself causes cancer, yet inflammation can contribute to proliferation, survival and migration of cancer cells by influencing the microenvironment around tumors.

    Hormones

    Some hormones play a role in the development of cancer by promoting cell proliferation. Insulin-like growth factors and their binding proteins play a key role in cancer cell proliferation, differentiation and apoptosis, suggesting possible involvement in carcinogenesis.

    Hormones are important agents in sex-related cancers such as cancer of the breast, endometrium, prostate, ovary, and testis, and also of thyroid cancer and bone cancer. For example, the daughters of women who have breast cancer have significantly higher levels of estrogen and progesterone than the daughters of women without breast cancer. These higher hormone levels may explain why these women have higher risk of breast cancer, even in the absence of a breast-cancer gene. Similarly, men of African ancestry have significantly higher levels of testosterone than men of European ancestry, and have a correspondingly much higher level of prostate cancer. Men of Asian ancestry, with the lowest levels of testosterone-activating androstanediol glucuronide, have the lowest levels of prostate cancer.

    Other factors are also relevant: obese people have higher levels of some hormones associated with cancer and a higher rate of those cancers. Women who take hormone replacement therapy have a higher risk of developing cancers associated with those hormones. On the other hand, people who exercise far more than average have lower levels of these hormones, and lower risk of cancer. Osteosarcoma may be promoted by growth hormones. Some treatments and prevention approaches leverage this cause by artificially reducing hormone levels, and thus discouraging hormone-sensitive cancers.

    Pathophysiology Main article: CarcinogenesisCancers are caused by a series of mutations. Each mutation alters the behavior of the cell somewhat.Genetics

    Cancer is fundamentally a disease of tissue growth regulation failure. In order for a normal cell to transform into a cancer cell, the genes which regulate cell growth and differentiation must be altered.

    The affected genes are divided into two broad categories. Oncogenes are genes which promote cell growth and reproduction. Tumor suppressor genes are genes which inhibit cell division and survival. Malignant transformation can occur through the formation of novel oncogenes, the inappropriate over-expression of normal oncogenes, or by the under-expression or disabling of tumor suppressor genes. Typically, changes in many genes are required to transform a normal cell into a cancer cell.

    Genetic changes can occur at different levels and by different mechanisms. The gain or loss of an entire chromosome can occur through errors in mitosis. More common are mutations, which are changes in the nucleotide sequence of genomic DNA.

    Large-scale mutations involve the deletion or gain of a portion of a chromosome. Genomic amplification occurs when a cell gains many copies (often 20 or more) of a small chromosomal locus, usually containing one or more oncogenes and adjacent genetic material. Translocation occurs when two separate chromosomal regions become abnormally fused, often at a characteristic location. A well-known example of this is the Philadelphia chromosome, or translocation of chromosomes 9 and 22, which occurs in chronic myelogenous leukemia, and results in production of the BCR-abl fusion protein, an oncogenic tyrosine kinase.

    Small-scale mutations include point mutations, deletions, and insertions, which may occur in the promoter region of a gene and affect its expression, or may occur in the gene''s coding sequence and alter the function or stability of its protein product. Disruption of a single gene may also result from integration of genomic material from a DNA virus or retrovirus, leading to the expression of viral oncogenes in the affected cell and its descendants.

    Replication of the enormous amount of data contained within the DNA of living cells will probabilistically result in some errors (mutations). Complex error correction and prevention is built into the process, and safeguards the cell against cancer. If significant error occurs, the damaged cell can "self-destruct" through programmed cell death, termed apoptosis. If the error control processes fail, then the mutations will survive and be passed along to daughter cells.

    Some environments make errors more likely to arise and propagate. Such environments can include the presence of disruptive substances called carcinogens, repeated physical injury, heat, ionising radiation, or hypoxia.

    The errors which cause cancer are self-amplifying and compounding, for example:

    The transformation of normal cell into cancer is akin to a chain reaction caused by initial errors, which compound into more severe errors, each progressively allowing the cell to escape the controls that limit normal tissue growth. This rebellion-like scenario becomes an undesirable survival of the fittest, where the driving forces of evolution work against the body''s design and enforcement of order. Once cancer has begun to develop, this ongoing process, termed clonal evolution drives progression towards more invasive stages.

    Characteristic abilities developed by cancers are divided into a number of categories. Six categories were originally proposed, in a 2000 article called The Hallmarks of Cancer by Douglas Hanahan and Robert Weinberg: evasion of apoptosis, self-sufficiency in growth signals, insensitivity to anti-growth signals, sustained angiogenesis, limitless replicative potential, and metastasis. Based on further work, the same authors added two more categories in 2011: reprogramming of energy metabolism and evasion of immune destruction.

    EpigeneticsThe central role of DNA damage and epigenetic defects in DNA repair genes in carcinogenesis

    Classically, cancer has been viewed as a set of diseases that are driven by progressive genetic abnormalities that include mutations in tumor-suppressor genes and oncogenes, and chromosomal abnormalities. However, it has become apparent that cancer is also driven by epigenetic alterations.

    Epigenetic alterations refer to functionally relevant modifications to the genome that do not involve a change in the nucleotide sequence. Examples of such modifications are changes in DNA methylation (hypermethylation and hypomethylation) and histone modification and changes in chromosomal architecture (caused by inappropriate expression of proteins such as HMGA2 or HMGA1). Each of these epigenetic alterations serves to regulate gene expression without altering the underlying DNA sequence. These changes may remain through cell divisions, last for multiple generations, and can be considered to be epimutations (equivalent to mutations).

    Epigenetic alterations occur frequently in cancers. As an example, Schnekenburger and Diederich listed protein coding genes that were frequently altered in their methylation in association with colon cancer. These included 147 hypermethylated and 27 hypomethylated genes. Of the hypermethylated genes, 10 were hypermethylated in 100% of colon cancers, and many others were hypermethylated in more than 50% of colon cancers.

    While large numbers of epigenetic alterations are found in cancers, the epigenetic alterations in DNA repair genes, causing reduced expression of DNA repair proteins, may be of particular importance. Such alterations are thought to occur early in progression to cancer and to be a likely cause of the genetic instability characteristic of cancers.

    Reduced expression of DNA repair genes causes deficient DNA repair. This is shown in the figure at the 4th level from the top. (In the figure, red wording indicates the central role of DNA damage and defects in DNA repair in progression to cancer.) When DNA repair is deficient DNA damages remain in cells at a higher than usual level (5th level from the top in figure), and these excess damages cause increased frequencies of mutation and/or epimutation (6th level from top of figure). Mutation rates increase substantially in cells defective in DNA mismatch repair or in homologous recombinational repair (HRR). Chromosomal rearrangements and aneuploidy also increase in HRR defective cells.

    Higher levels of DNA damage not only cause increased mutation (right side of figure), but also cause increased epimutation. During repair of DNA double strand breaks, or repair of other DNA damages, incompletely cleared sites of repair can cause epigenetic gene silencing.

    Deficient expression of DNA repair proteins due to an inherited mutation can cause increased risk of cancer. Individuals with an inherited impairment in any of 34 DNA repair genes (see article DNA repair-deficiency disorder) have an increased risk of cancer, with some defects causing up to a 100% lifetime chance of cancer (e.g. p53 mutations). Germ line DNA repair mutations are noted in a box on the left side of the figure, with an arrow indicating their contribution to DNA repair deficiency. However, such germline mutations (which cause highly penetrant cancer syndromes) are the cause of only about 1 percent of cancers.

    In sporadic cancers, deficiencies in DNA repair are occasionally caused by a mutation in a DNA repair gene, but are much more frequently caused by epigenetic alterations that reduce or silence expression of DNA repair genes. This is indicated in the figure at the 3rd level from the top. Many studies of heavy metal-induced carcinogenesis show that such heavy metals cause reduction in expression of DNA repair enzymes, some through epigenetic mechanisms. In some cases, DNA repair inhibition is proposed to be a predominant mechanism in heavy metal-induced carcinogenicity. In addition, there are frequent epigenetic alterations of the DNA sequences coding for small RNAs called microRNAs (or miRNAs). MiRNAs do not code for proteins, but can “target” protein-coding genes and reduce their expression.

    Cancers usually arise from an assemblage of mutations and epimutations that confer a selective advantage leading to clonal expansion (see Field defects in progression to cancer). Mutations, however, may not be as frequent in cancers as epigenetic alterations. An average cancer of the breast or colon can have about 60 to 70 protein-altering mutations, of which about 3 or 4 may be “driver” mutations, and the remaining ones may be “passenger” mutations.

    As pointed out above under genetic alterations, cancer is caused by failure to regulate tissue growth, when the genes which regulate cell growth and differentiation are altered. It has become clear that these alterations are caused by both DNA sequence mutation in oncogenes and tumor suppressor genes as well as by epigenetic alterations. The epigenetic deficiencies in expression of DNA repair genes, in particular, likely cause an increased frequency of mutations, some of which then occur in oncogenes and tumor suppressor genes.

    Metastasis Main article: Metastasis

    Metastasis is the spread of cancer to other locations in the body. The new tumors are called metastatic tumors, while the original is called the primary tumor. Almost all cancers can metastasize. Most cancer deaths are due to cancer that has spread from its primary site to other organs (metastasized).

    Metastasis is very common in the late stages of cancer, and it can occur via the blood or the lymphatic system or both. The typical steps in metastasis are local invasion, intravasation into the blood or lymph, circulation through the body, extravasation into the new tissue, proliferation, and angiogenesis. Different types of cancers tend to metastasize to particular organs, but overall the most common places for metastases to occur are the lungs, liver, brain, and the bones.

    DiagnosisChest x-ray showing lung cancer in the left lung.

    Most cancers are initially recognized either because of the appearance of signs or symptoms or through screening. Neither of these lead to a definitive diagnosis, which requires the examination of a tissue sample by a pathologist. People with suspected cancer are investigated with medical tests. These commonly include blood tests, X-rays, CT scans and endoscopy.

    Most people are distressed to learn that they have cancer. They may become extremely anxious and depressed. The risk of suicide in people with cancer is approximately double the normal risk.

    Classification Further information: List of cancer types and List of oncology-related terms

    Cancers are classified by the type of cell that the tumor cells resemble and is therefore presumed to be the origin of the tumor. These types include:

    Cancers are usually named using -carcinoma, -sarcoma or -blastoma as a suffix, with the Latin or Greek word for the organ or tissue of origin as the root. For example, cancers of the liver parenchyma arising from malignant epithelial cells is called hepatocarcinoma, while a malignancy arising from primitive liver precursor cells is called a hepatoblastoma, and a cancer arising from fat cells is called a liposarcoma. For some common cancers, the English organ name is used. For example, the most common type of breast cancer is called ductal carcinoma of the breast. Here, the adjective ductal refers to the appearance of the cancer under the microscope, which suggests that it has originated in the milk ducts.

    Benign tumors (which are not cancers) are named using -oma as a suffix with the organ name as the root. For example, a benign tumor of smooth muscle cells is called a leiomyoma (the common name of this frequently occurring benign tumor in the uterus is fibroid). Confusingly, some types of cancer use the -noma suffix, examples including melanoma and seminoma.

    Some types of cancer are named for the size and shape of the cells under a microscope, such as giant cell carcinoma, spindle cell carcinoma, and small-cell carcinoma.

    Pathology

    The tissue diagnosis given by the pathologist indicates the type of cell that is proliferating, its histological grade, genetic abnormalities, and other features of the tumor. Together, this information is useful to evaluate the prognosis of the patient and to choose the best treatment. Cytogenetics and immunohistochemistry are other types of testing that the pathologist may perform on the tissue specimen. These tests may provide information about the molecular changes (such as mutations, fusion genes, and numerical chromosome changes) that has happened in the cancer cells, and may thus also indicate the future behavior of the cancer (prognosis) and best treatment.

    Prevention

    Cancer prevention is defined as active measures to decrease the risk of cancer. The vast majority of cancer cases are due to environmental risk factors, and many, but not all, of these environmental factors are controllable lifestyle choices. Thus, cancer is considered a largely preventable disease. Greater than 30% of cancer deaths could be prevented by avoiding risk factors including: tobacco, overweight / obesity, an insufficient diet, physical inactivity, alcohol, sexually transmitted infections, and air pollution. Not all environmental causes are controllable, such as naturally occurring background radiation, and other cases of cancer are caused through hereditary genetic disorders, and thus it is not possible to prevent all cases of cancer.

    Dietary Main article: Diet and cancer

    While many dietary recommendations have been proposed to reduce the risk of cancer, the evidence to support them is not definitive. The primary dietary factors that increase risk are obesity and alcohol consumption; with a diet low in fruits and vegetables and high in red meat being implicated but not confirmed. A 2014 meta-analysis did not find a relationship between fruits and vegetables and cancer. Consumption of coffee is associated with a reduced risk of liver cancer. Studies have linked excessive consumption of red or processed meat to an increased risk of breast cancer, colon cancer, and pancreatic cancer, a phenomenon which could be due to the presence of carcinogens in meats cooked at high temperatures. Dietary recommendations for cancer prevention typically include an emphasis on vegetables, fruit, whole grains, and fish, and an avoidance of processed and red meat (beef, pork, lamb), animal fats, and refined carbohydrates.

    Medication

    The concept that medications can be used to prevent cancer is attractive, and evidence supports their use in a few defined circumstances. In the general population, NSAIDs reduce the risk of colorectal cancer however due to the cardiovascular and gastrointestinal side effects they cause overall harm when used for prevention. Aspirin has been found to reduce the risk of death from cancer by about 7%. COX-2 inhibitor may decrease the rate of polyp formation in people with familial adenomatous polyposis however are associated with the same adverse effects as NSAIDs. Daily use of tamoxifen or raloxifene has been demonstrated to reduce the risk of developing breast cancer in high-risk women. The benefit verses harm for 5-alpha-reductase inhibitor such as finasteride is not clear.

    Vitamins have not been found to be effective at preventing cancer, although low blood levels of vitamin D are correlated with increased cancer risk. Whether this relationship is causal and vitamin D supplementation is protective is not determined. Beta-Carotene supplementation has been found to increase lung cancer rates in those who are high risk. Folic acid supplementation has not been found effective in preventing colon cancer and may increase colon polyps. It is unclear if selenium supplementation has an effect.

    Vaccination

    Vaccines have been developed that prevent infection by some carcinogenic viruses. Human papillomavirus vaccine (Gardasil and Cervarix) decreases the risk of developing cervical cancer. The hepatitis B vaccine prevents infection with hepatitis B virus and thus decreases the risk of liver cancer. The administration of human papillomavirus and hepatitis B vaccinations is recommended when resources allow.

    Screening Main article: Cancer screening

    Unlike diagnosis efforts prompted by symptoms and medical signs, cancer screening involves efforts to detect cancer after it has formed, but before any noticeable symptoms appear. This may involve physical examination, blood or urine tests, or medical imaging.

    Cancer screening is currently not possible for many types of cancers, and even when tests are available, they may not be recommended for everyone. Universal screening or mass screening involves screening everyone. Selective screening identifies people who are known to be at higher risk of developing cancer, such as people with a family history of cancer. Several factors are considered to determine whether the benefits of screening outweigh the risks and the costs of screening. These factors include:

    Recommendations

    The U.S. Preventive Services Task Force (USPSTF) strongly recommends cervical cancer screening in women who are sexually active and have a cervix at least until the age of 65. They recommend that Americans be screened for colorectal cancer via fecal occult blood testing, sigmoidoscopy, or colonoscopy starting at age 50 until age 75. There is insufficient evidence to recommend for or against screening for skin cancer, oral cancer, lung cancer, or prostate cancer in men under 75. Routine screening is not recommended for bladder cancer, testicular cancer, ovarian cancer, pancreatic cancer, or prostate cancer.

    The USPSTF recommends mammography for breast cancer screening every two years for those 50–74 years old; however, they do not recommend either breast self-examination or clinical breast examination. A 2011 Cochrane review came to slightly different conclusions with respect to breast cancer screening stating that routine mammography may do more harm than good.

    Japan screens for gastric cancer using photofluorography due to the high incidence there.

    Genetic testing See also: Cancer syndrome Gene Cancer types
    BRCA1, BRCA2 Breast, ovarian, pancreatic
    HNPCC, MLH1, MSH2, MSH6, PMS1, PMS2 Colon, uterine, small bowel, stomach, urinary tract

    Genetic testing for individuals at high-risk of certain cancers is recommended. Carriers of these mutations may then undergo enhanced surveillance, chemoprevention, or preventative surgery to reduce their subsequent risk.

    Management Main articles: Management of cancer and oncology

    Many treatment options for cancer exist, with the primary ones including surgery, chemotherapy, radiation therapy, hormonal therapy, targeted therapy and palliative care. Which treatments are used depends upon the type, location, and grade of the cancer as well as the person''s health and wishes. The treatment intent may be curative or not curative.

    Chemotherapy

    Chemotherapy is the treatment of cancer with one or more cytotoxic anti-neoplastic drugs (chemotherapeutic agents) as part of a standardized regimen. The term encompasses any of a large variety of different anticancer drugs, which are divided into broad categories such as alkylating agents and antimetabolites. Traditional chemotherapeutic agents act by killing cells that divide rapidly, one of the main properties of most cancer cells.

    Targeted therapy is a form of chemotherapy which target specific molecular differences between cancer and normal cells. The first targeted therapies to be developed blocked the estrogen receptor molecule, inhibiting the growth of breast cancer. Another common example is the class of Bcr-Abl inhibitors, which are used to treat chronic myelogenous leukemia (CML). Currently, there are targeted therapies for breast cancer, multiple myeloma, lymphoma, prostate cancer, melanoma and other cancers.

    The efficacy of chemotherapy depends on the type of cancer and the stage. In combination with surgery, chemotherapy has proven useful in a number of different cancer types including: breast cancer, colorectal cancer, pancreatic cancer, osteogenic sarcoma, testicular cancer, ovarian cancer, and certain lung cancers. The overall effectiveness ranges from being curative for some cancers, such as some leukemias, to being ineffective, such as in some brain tumors, to being needless in others, like most non-melanoma skin cancers. The effectiveness of chemotherapy is often limited by toxicity to other tissues in the body. Even when it is impossible for chemotherapy to provide a permanent cure, chemotherapy may be useful to reduce symptoms like pain or to reduce the size of an inoperable tumor in the hope that surgery will be possible in the future.

    Radiation

    Radiation therapy involves the use of ionizing radiation in an attempt to either cure or improve the symptoms of cancer. It works by damaging the DNA of cancerous tissue leading to cellular death. To spare normal tissues (such as skin or organs which radiation must pass through to treat the tumor), shaped radiation beams are aimed from several angles of exposure to intersect at the tumor, providing a much larger absorbed dose there than in the surrounding, healthy tissue. As with chemotherapy, different cancers respond differently to radiation therapy.

    Radiation therapy is used in about half of all cases and the radiation can be from either internal sources in the form of brachytherapy or external sources. Radiation is typically used in addition to surgery and or chemotherapy but for certain types of cancer, such as early head and neck cancer, may be used alone. For painful bone metastasis, it has been found to be effective in about 70% of people.

    Surgery

    Surgery is the primary method of treatment of most isolated solid cancers and may play a role in palliation and prolongation of survival. It is typically an important part of making the definitive diagnosis and staging the tumor as biopsies are usually required. In localized cancer surgery typically attempts to remove the entire mass along with, in certain cases, the lymph nodes in the area. For some types of cancer this is all that is needed to eliminate the cancer.

    Palliative care

    Palliative care refers to treatment which attempts to make the person feel better and may or may not be combined with an attempt to treat the cancer. Palliative care includes action to reduce the physical, emotional, spiritual, and psycho-social distress experienced by people with cancer. Unlike treatment that is aimed at directly killing cancer cells, the primary goal of palliative care is to improve the person''s quality of life.

    People at all stages of cancer treatment should have some kind of palliative care to provide comfort. In some cases, medical specialty professional organizations recommend that people and physicians respond to cancer only with palliative care and not with cure-directed therapy. This includes:

  • people with low performance status, corresponding with limited ability to care for themselves
  • people who received no benefit from prior evidence-based treatments
  • people who are not eligible to participate in any appropriate clinical trial
  • people for whom the physician sees no strong evidence that treatment would be effective
  • Palliative care is often confused with hospice and therefore only involved when people approach end of life. Like hospice care, palliative care attempts to help the person cope with the immediate needs and to increase the person''s comfort. Unlike hospice care, palliative care does not require people to stop treatment aimed at prolonging their lives or curing the cancer.

    Multiple national medical guidelines recommend early palliative care for people whose cancer has produced distressing symptoms (pain, shortness of breath, fatigue, nausea) or who need help coping with their illness. In people who have metastatic disease when first diagnosed, oncologists should consider a palliative care consult immediately. Additionally, an oncologist should consider a palliative care consult in any person they feel has less than 12 months of life even if continuing aggressive treatment.

    Immunotherapy Main article: Cancer immunotherapy

    A variety of therapies using immunotherapy, stimulating or helping the immune system to fight cancer, have come into use since 1997, and this continues to be an area of very active research.

    Alternative medicine

    Complementary and alternative cancer treatments are a diverse group of health care systems, practices, and products that are not part of conventional medicine. "Complementary medicine" refers to methods and substances used along with conventional medicine, while "alternative medicine" refers to compounds used instead of conventional medicine. Most complementary and alternative medicines for cancer have not been rigorously studied or tested. Some alternative treatments have been investigated and shown to be ineffective but still continue to be marketed and promoted. Cancer researcher Andrew J. Vickers has stated: "The label ''unproven'' is inappropriate for such therapies; it is time to assert that many alternative cancer therapies have been ''disproven''."

    Edzard Ernst has stated:

    "... any alternative cancer cure is bogus by definition. There will never be an alternative cancer cure. Why? Because if something looked halfway promising, then mainstream oncology would scrutinize it, and if there is anything to it, it would become mainstream almost automatically and very quickly. All curative "alternative cancer cures" are based on false claims, are bogus, and, I would say, even criminal."Prognosis See also: List of cancer mortality rates and Cancer survivor

    Cancer has a reputation as a deadly disease. Taken as a whole, about half of people receiving treatment for invasive cancer (excluding carcinoma in situ and non-melanoma skin cancers) die from cancer or its treatment. Survival is worse in the developing world, partly because the types of cancer that are most common there are at present harder to treat than those associated with the lifestyle of developed countries. However, the survival rates vary dramatically by type of cancer, and by the stage at which it is diagnosed, with the range running from the great majority of people surviving to almost no one surviving as long as five years after diagnosis. Once a cancer has metastasized or spread beyond its original site the prognosis normally becomes much worse.

    Those who survive cancer are at increased risk of developing a second primary cancer at about twice the rate of those never diagnosed with cancer. The increased risk is believed to be primarily due to the same risk factors that produced the first cancer, partly due to the treatment for the first cancer, and potentially related to better compliance with screening.

    Predicting either short-term or long-term survival is difficult and depends on many factors. The most important factors are the particular kind of cancer and the patient''s age and overall health. People who are frail with many other health problems have lower survival rates than otherwise healthy people. A centenarian is unlikely to survive for five years even if the treatment is successful. People who report a higher quality of life tend to survive longer. People with lower quality of life may be affected by major depressive disorder and other complications from cancer treatment and/or disease progression that both impairs their quality of life and reduces their quantity of life. Additionally, patients with worse prognoses may be depressed or report a lower quality of life directly because they correctly perceive that their condition is likely to be fatal.

    Epidemiology Main article: Epidemiology of cancer

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