Etymology and definitions
The word comes from the ancient Greek , meaning 'crab' and 'tumor'. Greek physicians Hippocrates and Galen, among others, noted the similarity of crabs to some tumors with swollen veins. The word was introduced in English in the modern medical sense around 1600. Cancers comprise a large family of diseases that involve abnormalSigns and symptoms
When cancer begins, it produces no symptoms. Signs and symptoms appear as the mass grows or ulcerates. The findings that result depend on cancer's type and location. Few symptoms are specific. Many frequently occur in individuals who have other conditions. Cancer can be difficult to diagnose and can be considered a " great imitator." People may become anxious or depressed post-diagnosis. The risk of suicide in people with cancer is approximately double.Local symptoms
Local symptoms may occur due to the mass of the tumor or its ulceration. For example, mass effects from lung cancer can block the bronchus resulting in cough or pneumonia;Systemic symptoms
Systemic symptoms may occur due to the body's response to the cancer. This may include fatigue, unintentional weight loss, or skin changes. Some cancers can cause a systemic inflammatory state that leads to ongoing muscle loss and weakness, known as cachexia. Some cancers, such asMetastasis
Metastasis is the spread of cancer to other locations in the body. The dispersed 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 metastasized. Metastasis is common in the late stages of cancer and it can occur via the blood or theCauses
The majority of cancers, some 90–95% of cases, are due to genetic mutations from environmental and lifestyle factors. The remaining 5–10% are due to inherited genetics. '' Environmental'' refers to any cause that is not inherited, such as lifestyle, economic, and behavioral factors and not merely pollution. Common environmental factors that contribute to cancer death include tobacco use (25–30%), diet and obesity (30–35%), infections (15–20%),Chemicals
Exposure to particular substances have been linked to specific types of cancer. These substances are called '' carcinogens''. Tobacco smoke, for example, causes 90% of lung cancer. It also causes cancer in theDiet and exercise
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 cancer deaths. A UK study including data on over 5 million people showed higherInfection
Worldwide approximately 18% of cancer deaths are related to infectious diseases. This proportion ranges 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 cancer bacteria and parasites may also play a role. Oncoviruses (viruses that can cause cancer) include human papillomavirus (Radiation
Radiation exposure such as ultraviolet radiation and radioactive material is a risk factor for cancer. Many non-melanoma skin cancers are due to ultraviolet radiation, mostly from sunlight. Sources of ionizing radiation includeHeredity
The vast majority of cancers are non-hereditary (sporadic). Hereditary cancers are primarily caused by an inherited genetic defect. Less than 0.3% of the population are carriers of a genetic mutation that has a large effect on cancer risk and these cause less than 3–10% of 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 withPhysical agents
Some substances cause cancer primarily through their physical, rather than chemical, effects. A prominent example of this is prolonged exposure toHormones
Some hormones play a role in the development of cancer by promoting cell growth, 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 testicle, 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 their 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 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 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 (menopause), 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.Autoimmune diseases
There is an association between celiac disease and an increased risk of all cancers. People with untreated celiac disease have a higher risk, but this risk decreases with time after diagnosis and strict treatment, probably due to the adoption of a gluten-free diet, which seems to have a protective role against development of malignancy in people with celiac disease. However, the delay in diagnosis and initiation of a gluten-free diet seems to increase the risk of malignancies. Rates of gastrointestinal cancers are increased in people with Crohn's disease and ulcerative colitis, due to chronic inflammation. Also, immunotherapy, immunomodulators and biological therapy for inflammatory bowel disease, biologic agents used to treat these diseases may promote developing extra-intestinal malignancies.Pathophysiology
Genetics
Cancer is fundamentally a disease of tissue growth regulation. For a normal cell to malignant transformation, transform into a cancer cell, the genes that regulate cell growth and differentiation must be altered. The affected genes are divided into two broad categories. Oncogenes are genes that promote cell growth and reproduction. Tumor suppressor genes are genes that 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 multiple 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. Gene duplication, Genomic amplification occurs when a cell gains 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. Small-scale mutations include point mutations, deletions, and insertions, which may occur in the promoter (genetics), promoter region 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, leading to the expression of ''viral'' oncogenes in the affected cell and its descendants. Replication of the data contained within the DNA of living cells will probability, probabilistically result in some errors (mutations). Complex error correction and prevention are built into the process and safeguard the cell against cancer. If a 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 cell division, 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 (medical), hypoxia. The errors that cause cancer are self-amplifying and compounding, for example: * A mutation in the error-correcting machinery of a cell might cause that cell and its children to accumulate errors more rapidly. * A further mutation in an oncogene might cause the cell to reproduce more rapidly and more frequently than its normal counterparts. * A further mutation may cause loss of a tumor suppressor gene, disrupting the apoptosis signaling pathway and immortalizing the cell. * A further mutation in the signaling machinery of the cell might send error-causing signals to nearby cells. The transformation of a 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 more controls that limit normal tissue growth. This rebellion-like scenario is 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 ''Somatic evolution in cancer, clonal evolution'', drives progression towards more invasive cancer staging, stages. Clonal evolution leads to intra-tumour heterogeneity (cancer cells with heterogeneous mutations) that complicates designing effective treatment strategies and requires an Evolutionary therapy, evolutionary approach to designing treatment. Characteristic abilities developed by cancers are divided into categories, specifically evasion of apoptosis, self-sufficiency in growth signals, insensitivity to anti-growth signals, sustained angiogenesis, limitless replicative potential, metastasis, reprogramming of energy metabolism and evasion of immune destruction.Epigenetics
The classical view of cancer is a set of diseases driven by progressive genetic abnormalities that include mutations in tumor-suppressor genes and oncogenes, and in chromosome, chromosomal abnormalities. A role for Epigenetics, epigenetic alterations was identified in the early 21st century. Epigenetics, Epigenetic alterations are functionally relevant modifications to the genome that do not change the nucleotide sequence. Examples of such modifications are changes in DNA methylation (hypermethylation and hypomethylation), histone modification and changes in chromosomal architecture (caused by inappropriate expression of proteins such as HMGA2 or HMGA1). Each of these alterations regulates gene expression without altering the underlying DNA sequence. These changes may remain through cell divisions, endure for multiple generations, and can be considered as equivalent to mutations. Epigenetic alterations occur frequently in cancers. As an example, one study 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 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 may occur early in progression to cancer and are a possible cause of the Genome instability, genetic instability characteristic of cancers. Reduced expression of DNA repair genes disrupts 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 damage remains in cells at a higher than usual level (5th level) and causes increased frequencies of mutation and/or epimutation (6th level). 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 cause increased mutation (right side of figure) and increased epimutation. During repair of DNA double strand breaks, or repair of other DNA damage, incompletely cleared repair sites can cause epigenetic gene silencing. Deficient expression of DNA repair proteins due to an inherited mutation can increase cancer risks. Individuals with an inherited impairment in any of 34 DNA repair genes (see article DNA repair-deficiency disorder) have increased cancer risk, with some defects ensuring a 100% lifetime chance of cancer (e.g. p53 mutations). Germ line DNA repair mutations are noted on the figure's left side. 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. Many studies of heavy metal-induced carcinogenesis show that such heavy metals cause a reduction in expression of DNA repair enzymes, some through epigenetic mechanisms. DNA repair inhibition is proposed to be a predominant mechanism in heavy metal-induced carcinogenicity. In addition, frequent epigenetic alterations of the DNA sequences code 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 Neoplasm#Field defects in progression to cancer, 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 three or four may be "driver" mutations and the remaining ones may be "passenger" mutations.Metastasis
Metastasis is the spread of cancer to other locations in the body. The dispersed 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 metastasized. Metastasis is common in the late stages of cancer and it can occur via the blood or theMetabolism
Normal cells typically generate only about 30% of energy from glycolysis, whereas most cancers rely on glycolysis for energy production (Warburg effect (oncology), Warburg effect). But a minority of cancer types rely on oxidative phosphorylation as the primary energy source, including lymphoma, leukemia, and endometrial cancer. Even in these cases, however, the use of glycolysis as an energy source rarely exceeds 60%. A few cancers use glutamine as the major energy source, partly because it provides nitrogen required for nucleotide (DNA, RNA) synthesis. Cancer stem cells often use oxidative phosphorylation or glutamine as a primary energy source. Several studies have indicated that the enzyme sirtuin 6 is selectively inactivated during oncogenesis in a variety of tumor types by inducing glycolysis. Another sirtuin, sirtuin 3 inhibits cancers that depend upon glycolysis, but promotes cancers that depend upon oxidative phosphorylation. A low-carbohydrate diet (ketogenic diet) has sometimes been recommended as a supportive therapy for cancer treatment.Diagnosis
Most cancers are initially recognized either because of the appearance of signs or symptoms or through cancer screening, screening. Neither of these leads to a definitive diagnosis, which requires the examination of a tissue sample by a anatomical pathology, pathologist. People with suspected cancer are investigated with medical tests. These commonly include blood tests, Projectional radiography, X-rays, (contrast CT, contrast) CT scans and endoscopy. The tissue medical diagnosis, diagnosis from the biopsy indicates the type of cell that is proliferating, its histological grade, genetic abnormalities and other features. Together, this information is useful to evaluate the prognosis and to choose the best treatment. Cytogenetics and immunohistochemistry are other types of tissue tests. These tests provide information about molecular changes (such as mutations, fusion genes and numerical chromosome changes) and may thus also indicate the prognosis and best treatment. Cancer diagnosis can cause psychological distress and psychosocial interventions, such as talking therapy, may help people with this.Classification
Cancers are classified by the List of distinct cell types in the adult human body, type of cell that the tumor cells resemble and is therefore presumed to be the origin of the tumor. These types include: * Carcinoma: Cancers derived from epithelium, epithelial cells. This group includes many of the most common cancers and include nearly all those in the breast cancer, breast, prostate cancer, prostate, lung cancer, lung, pancreas and Colorectal cancer, colon. * Sarcoma: Cancers arising from connective tissue (i.e. bone, cartilage, fat, nerve), each of which develops from cells originating in mesenchyme, mesenchymal cells outside the bone marrow. * Lymphoma and leukemia: These two classes arise from hematopoietic (blood-forming) cells that leave the marrow and tend to mature in the lymph nodes and blood, respectively. * Germ cell tumor: Cancers derived from pluripotent cells, most often presenting in the testicular cancer, testicle or the ovarian cancer, ovary (seminoma and dysgerminoma, respectively). * Blastoma: Cancers derived from immature "precursor" cells or embryonic tissue. Cancers are usually named using ''-carcinoma'', ''-sarcoma'' or ''-blastoma'' as a suffix, with the Latin or Greek word for the organ (anatomy), organ or tissue of origin as the root. For example, cancers of the liver parenchyma arising from malignant epithelial cells is called ''hepatocellular carcinoma, 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 ''mammary ductal carcinoma, ductal carcinoma of the breast''. Here, the adjective ''ductal'' refers to the appearance of 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 ''uterine fibroid, fibroid''). Confusingly, some types of cancer use the ''-noma'' suffix, examples includingPrevention
Cancer prevention is defined as active measures to decrease cancer risk. The vast majority of cancer cases are due to environmental risk factors. Many of these environmental factors are controllable lifestyle choices. Thus, cancer is generally preventable. Between 70% and 90% of common cancers are due to environmental factors and therefore potentially preventable. Greater than 30% of cancer deaths could be prevented by avoiding risk factors including: tobacco, overweight, excess weight/ obesity, poor diet, physical inactivity, alcohol (drug), alcohol, sexually transmitted infections and air pollution. Further, poverty could be considered as an indirect risk factor in human cancers. Not all environmental causes are controllable, such as naturally occurring background radiation and cancers caused through hereditary genetic disorders and thus are not preventable via personal behavior. In 2019, ~44% of all cancer deaths – or ~4.5 M deaths or ~105 million lost disability-adjusted life years – were List of causes of death by rate#Underlying causes, due to known clearly preventable risk factors, led by smoking, Alcohol and health, alcohol use and obesity, high BMI, according to a Global Burden of Disease Study, GBD Systematic review, systematic analysis.Dietary
While many dietary recommendations have been proposed to reduce cancer risks, the evidence to support them is not definitive. The primary dietary factors that increase risk are obesity and alcohol consumption. Diets low in fruits and vegetables and high in red meat have been implicated but reviews and meta-analyses do not come to a consistent conclusion. A 2014 meta-analysis found no relationship between fruits and vegetables and cancer. Coffee is associated with a reduced risk of liver cancer. Studies have linked excessive consumption of red meat, red or processed meat to an increased risk of breast cancer, Colorectal cancer, colon cancer and pancreatic cancer, a phenomenon that could be due to the presence of carcinogens in meats cooked at high temperatures. In 2015 the International Agency for Research on Cancer, IARC reported that eating processed meat (e.g., bacon, ham, hot dogs, sausages) and, to a lesser degree, red meat was linked to some cancers. Healthy diet, 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, pickled foods and Carbohydrate#Nutrition, refined carbohydrates.Medication
Medications can be used to prevent cancer in a few circumstances. In the general population, Non-steroidal anti-inflammatory drug, NSAIDs reduce the risk ofVaccination
Vaccines have been developed that prevent infection by some carcinogenic viruses. HPV vaccine, Human papillomavirus vaccine (Gardasil and Cervarix) decrease the risk of developingScreening
Unlike diagnostic 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 test, blood or urinalysis, urine tests orRecommendations
U.S. Preventive Services Task Force
The U.S. Preventive Services Task Force (USPSTF) issues recommendations for various cancers: * Strongly recommendsJapan
Screens for gastric cancer using photofluorography due to the high incidence there.Genetic testing
Genetic testing for individuals at high-risk of certain cancers is recommended by unofficial groups. Carriers of these mutations may then undergo enhanced surveillance, chemoprevention, or preventative surgery to reduce their subsequent risk.Management
Many treatment options for cancer exist. The primary ones include surgery, chemotherapy, radiation therapy, hormonal therapy (oncology), hormonal therapy, targeted therapy and palliative care. Which treatments are used depends on the type, location and grade of the cancer as well as the patient's health and preferences. The therapy#By treatment intent, treatment intent may or may not be curative.Chemotherapy
Chemotherapy is the treatment of cancer with one or more Cytotoxicity, cytotoxic anti-neoplastic drugs (list of chemotherapeutic agents, chemotherapeutic agents) as part of a chemotherapy regimen, standardized regimen. The term encompasses a variety of drugs, which are divided into broad categories such as Alkylating antineoplastic agent, alkylating agents and antimetabolites. Traditional chemotherapeutic agents act by killing cells that divide rapidly, a critical property of most cancer cells. It was found that providing combined cytotoxic drugs is better than a single drug, a process called the combination therapy, which has an advantage in the statistics of survival and response to the tumor and in the progress of the disease. A Cochrane review concluded that combined therapy was more effective to treat metastasized breast cancer. However, generally it is not certain whether combination chemotherapy leads to better health outcomes, when both survival and toxicity are considered. Targeted therapy is a form of chemotherapy that targets specific molecular differences between cancer and normal cells. The first targeted therapies blocked the estrogen receptor molecule, inhibiting the growth of breast cancer. Another common example is the class of Bcr-Abl tyrosine-kinase inhibitor, Bcr-Abl inhibitors, which are used to treat chronic myelogenous leukemia (CML). Currently, targeted therapies exist for many of the most common cancer types, including bladder cancer, breast cancer,Radiation
Radiation therapy involves the use ofSurgery
Surgery is the primary method of treatment for most isolated, solid cancers and may play a role in palliation and prolongation of survival. It is typically an important part of definitive diagnosis and staging of tumors, 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 sufficient to eliminate the cancer.Holland Chp. 40Palliative care
Palliative care is treatment that attempts to help the patient feel better and may be combined with an attempt to treat the cancer. Palliative care includes action to reduce physical, emotional, spiritual and psycho-social distress. Unlike treatment that is aimed at directly killing cancer cells, the primary goal of palliative care is to improve quality of life (healthcare), quality of life. People at all stages of cancer treatment typically receive some kind of palliative care. In some cases, Specialty (medicine), medical specialty professional organizations recommend that patients and physicians respond to cancer only with palliative care. This applies to patients who: # display low performance status, implying limited ability to care for themselves # received no benefit from prior Evidence-based medicine, evidence-based treatments # are not eligible to participate in any appropriate clinical trial # no strong evidence implies that treatment would be effective Palliative care may be confused with hospice and therefore only indicated when people approach End-of-life care, end of life. Like hospice care, palliative care attempts to help the patient cope with their immediate needs and to increase comfort. Unlike hospice care, palliative care does not require people to stop treatment aimed at the cancer. Multiple national medical guidelines recommend early palliative care for patients whose cancer has produced distressing symptoms or who need help coping with their illness. In patients first diagnosed with metastatic disease, palliative care may be immediately indicated. Palliative care is indicated for patients with a prognosis of less than 12 months of life even given aggressive treatment.Immunotherapy
A variety of therapies using Cancer immunotherapy, immunotherapy, stimulating or helping the immune system to fight cancer, have come into use since 1997. Approaches include Monoclonal antibody, antibodies, checkpoint therapy, and adoptive cell transfer.Laser therapy
Laser therapy uses high-intensity light to treat cancer by shrinking or destroying tumors or precancerous growths. Lasers are most commonly used to treat superficial cancers that are on the surface of the body or the lining of internal organs. It is used to treat basal cell skin cancer and the very early stages of others like cervical, penile, vaginal, vulvar, and non-small cell lung cancer. It is often combined with other treatments, such as surgery, chemotherapy, or radiation therapy. Laser ablation, Laser-induced interstitial thermotherapy (LITT), or interstitial laser Laser coagulation, photocoagulation, uses lasers to treat some cancers using hyperthermia, which uses heat to shrink tumors by damaging or killing cancer cells. Laser are more precise than surgery and cause less damage, pain, bleeding, swelling, and scarring. A disadvantage is surgeons must have specialized training. It may be more expensive than other treatments.Alternative medicine
Alternative cancer treatments, Complementary and alternative cancer treatments are a diverse group of therapies, 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 studied or tested using conventional techniques such as clinical trials. Some alternative treatments have been investigated and shown to be ineffective but still continue to be marketed and promoted. Cancer researcher Andrew J. Vickers stated, "The label 'unproven' is inappropriate for such therapies; it is time to assert that many alternative cancer therapies have been 'disproven'."Prognosis
Survival rates vary by cancer type and by the stage at which it is diagnosed, ranging from majority survival to complete mortality five years after diagnosis. Once a cancer has metastasized, prognosis normally becomes much worse. About half of patients receiving treatment for invasive cancer (excluding carcinoma in situ, carcinoma ''in situ'' and non-melanoma skin cancers) die from that cancer or its treatment. A majority of cancer deaths are due to metastases of the primary tumor. Survival is worse in the developing world, partly because the types of cancer that are most common there are harder to treat than those associated with developed countries. Those who survive cancer develop a second primary cancer at about twice the rate of those never diagnosed. The increased risk is believed to be due to the random chance of developing any cancer, the likelihood of surviving the first cancer, the same risk factors that produced the first cancer, unwanted side effects of treating the first cancer (particularly radiation therapy), and better compliance with screening. Predicting short- or long-term survival depends on many factors. The most important are the cancer type and the patient's age and overall health. Those who are wikt:frailty, frail with other health problems have lower survival rates than otherwise healthy people. Centenarians are unlikely to survive for five years even if 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, depression and other complications and/or disease progression that both impairs quality and quantity of life. Additionally, patients with worse prognoses may be depressed or report poorer quality of life because they perceive that their condition is likely to be fatal. People with cancer have an increased risk of venous thromboembolism, blood clots in their veins which can be life-threatening. The use of Anticoagulant, blood thinners such as heparin decrease the risk of blood clots but have not been shown to increase survival in people with cancer. People who take blood thinners also have an increased risk of bleeding. Although extremely rare, some forms of cancer, even from an advanced stage, can heal spontaneously. This phenomenon is known as the spontaneous remission.Epidemiology
Estimates are that in 2018, 18.1 million new cases of cancer and 9.6 million deaths occur globally. About 20% of males and 17% of females will get cancer at some point in time while 13% of males and 9% of females will die from it. In 2008, approximately 12.7 million cancers were diagnosis, diagnosed (excluding non-melanoma skin cancers and other non-invasive cancers) and in 2010 nearly 7.98 million people died. Cancers account for approximately 16% of deaths. The most common are lung cancer (1.76 million deaths),History
Cancer has existed for all of human history. The earliest written record regarding cancer is from circa 1600 BC in the Egyptian Edwin Smith Papyrus and describes breast cancer. Hippocrates ( – ) described several kinds of cancer, referring to them with the Greek language, Greek word wikt:καρκίνος#Ancient Greek, καρκίνος ''karkinos'' (crab or crayfish). This name comes from the appearance of the cut surface of a solid malignant tumor, with "the veins stretched on all sides as the animal the crab has its feet, whence it derives its name". Galen stated that "cancer of the breast is so called because of the fancied resemblance to a crab given by the lateral prolongations of the tumor and the adjacent distended veins". Aulus Cornelius Celsus, Celsus ( – 50 AD) translated ''karkinos'' into the Latin ''cancer'', also meaning crab and recommended surgery as treatment. Galen (2nd century AD) disagreed with the use of surgery and recommended purgatives instead. These recommendations largely stood for 1000 years. In the 15th, 16th and 17th centuries, it became acceptable for doctors to dissection, 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 René Descartes, 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. The physician John Hill described tobacco sniffing as the cause of nose cancer in 1761. This was followed by the report in 1775 by British surgeon Percivall Pott that chimney sweeps' carcinoma, a cancer of the scrotum, was a common disease among chimney sweeps. 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.Society and culture
Although many diseases (such as heart failure) may have a worse prognosis than most cases of cancer, cancer is the subject of widespread fear and taboos. The euphemism of "a long illness" to describe cancers leading to death is still commonly used in obituaries, rather than naming the disease explicitly, reflecting an apparent social stigma, stigma. Cancer is also euphemised as "the C-word"; Macmillan Cancer Support uses the term to try to lessen the fear around the disease. In Nigeria, one local name for cancer translates into English as "the disease that cannot be cured". This deep belief that cancer is necessarily a difficult and usually deadly disease is reflected in the systems chosen by society to compile cancer statistics: the most common form of cancer—non-melanoma skin cancers, accounting for about one-third of cancer cases worldwide, but very few deaths—are excluded from cancer statistics specifically because they are easily treated and almost always cured, often in a single, short, outpatient procedure. Western conceptions of patients' rights for people with cancer include a duty to fully disclose the medical situation to the person, and the right to engage in Shared decision-making in medicine, shared decision-making in a way that respects the person's own values. In other cultures, other rights and values are preferred. For example, most African cultures value whole families rather than individualism. In parts of Africa, a diagnosis is commonly made so late that cure is not possible, and treatment, if available at all, would quickly bankrupt the family. As a result of these factors, African healthcare providers tend to let family members decide whether, when and how to disclose the diagnosis, and they tend to do so slowly and circuitously, as the person shows interest and an ability to cope with the grim news. People from Asian and South American countries also tend to prefer a slower, less candid approach to disclosure than is idealized in the United States and Western Europe, and they believe that sometimes it would be preferable not to be told about a cancer diagnosis. In general, disclosure of the diagnosis is more common than it was in the 20th century, but full disclosure of the prognosis is not offered to many patients around the world. In the United States and some other cultures, cancer is regarded as a disease that must be "fought" to end the "civil insurrection"; a War on Cancer was declared in the US. Military metaphors are particularly common in descriptions of cancer's human effects, and they emphasize both the state of the patient's health and the need to take immediate, decisive actions himself rather than to delay, to ignore or to rely entirely on others. The military metaphors also help rationalize radical, destructive treatments. In the 1970s, a relatively popular alternative cancer treatment in the US was a specialized form of talk therapy, based on the idea that cancer was caused by a bad attitude. People with a "cancer personality"—depressed, repressed, self-loathing and afraid to express their emotions—were believed to have manifested cancer through subconscious desire. Some psychotherapists said that treatment to change the patient's outlook on life would cure the cancer. Among other effects, this belief allowed society to Victim blaming, blame the victim for having caused the cancer (by "wanting" it) or having prevented its cure (by not becoming a sufficiently happy, fearless and loving person). It also increased patients' anxiety, as they incorrectly believed that natural emotions of sadness, anger or fear shorten their lives. The idea was ridiculed by Susan Sontag, who published ''Illness as Metaphor'' while recovering from treatment for breast cancer in 1978. Although the original idea is now generally regarded as nonsense, the idea partly persists in a reduced form with a widespread, but incorrect, belief that deliberately cultivating a habit of Optimism, positive thinking will increase survival. This notion is particularly strong in breast cancer culture. One idea about why people with cancer are blamed or stigmatized, called the just-world hypothesis, is that blaming cancer on the patient's actions or attitudes allows the blamers to regain a sense of control. This is based upon the blamers' belief that the world is fundamentally just and so any dangerous illness, like cancer, must be a type of punishment for bad choices, because in a just world, bad things would not happen to good people.Economic effect
The total health care expenditure on cancer in the US was estimated to be $80.2 billion in 2015. Even though cancer-related health care expenditure have increased in absolute terms during recent decades, the share of health expenditure devoted to cancer treatment has remained close to 5% between the 1960s and 2004. A similar pattern has been observed in Europe where about 6% of all health care expenditure are spent on cancer treatment. In addition to health care expenditure and financial toxicity, cancer causes indirect costs in the form of productivity losses due to sick days, permanent incapacity and disability as well as premature death during working age. Cancer causes also costs for informal care. Indirect costs and informal care costs are typically estimated to exceed or equal the health care costs of cancer.Workplace
In the United States, cancer is included as a protected condition by the Equal Employment Opportunity Commission (EEOC), mainly due to the potential for cancer having discriminating effects on workers.U.S. Equal Employment Opportunity Commission. "Questions & Answers about Cancer in the Workplace and the Americans with Disabilities Act (ADA)." https://www.eeoc.gov/laws/types/cancer.cfm Discrimination in the workplace could occur if an employer holds a false belief that a person with cancer is not capable of doing a job properly, and may ask for more sick leave than other employees. Employers may also make hiring or firing decisions based on misconceptions about cancer disabilities, if present. The EEOC provides interview guidelines for employers, as well as lists of possible solutions for assessing and accommodating employees with cancer.Research
Because cancer is a class of diseases, it is unlikely that there will ever be a single "cure for cancer" any more than there will be a single treatment for all infectious diseases. Angiogenesis inhibitors were once incorrectly thought to have potential as a "silver bullet" treatment applicable to many types of cancer. Angiogenesis inhibitors and other cancer therapeutics are used in combination to reduce cancer morbidity and mortality. Experimental cancer treatments are studied in clinical trials to compare the proposed treatment to the best existing treatment. Treatments that succeeded in one cancer type can be tested against other types. Diagnostic tests are under development to better target the right therapies to the right patients, based on their individual biology. Cancer research focuses on the following issues: * Agents (e.g. viruses) and events (e.g. mutations) that cause or facilitate genetic changes in cells destined to become cancer. * The precise nature of the genetic damage and the genes that are affected by it. * The consequences of those genetic changes on the biology of the cell, both in generating the defining properties of a cancer cell and in facilitating additional genetic events that lead to further progression of the cancer. The improved understanding of molecular biology and cell biology, cellular biology due to cancer research has led to new treatments for cancer since US President Richard Nixon declared the "War on Cancer" in 1971. Since then, the country has spent over $200 billion on cancer research, including resources from public and private sectors. The cancer death rate (adjusting for size and age of the population) declined by five percent between 1950 and 2005. Competition for financial resources appears to have suppressed the creativity, cooperation, risk-taking and original thinking required to make fundamental discoveries, unduly favoring low-risk research into small incremental advancements over riskier, more innovative research. Other consequences of competition appear to be many studies with dramatic claims whose results cannot be replicated and perverse incentives that encourage grantee institutions to grow without making sufficient investments in their own faculty and facilities. Virotherapy, which uses convert viruses, is being studied. In the wake of the COVID-19 pandemic, there has been a worry that cancer research and treatment are slowing down.Pregnancy
Cancer affects approximately 1 in 1,000 pregnant women. The most common cancers found during pregnancy are the same as the most common cancers found in non-pregnant women during childbearing ages: breast cancer, cervical cancer, leukemia, lymphoma, melanoma, ovarian cancer and colorectal cancer. Diagnosing a new cancer in a pregnant woman is difficult, in part because any symptoms are commonly assumed to be a normal discomfort associated with pregnancy. As a result, cancer is typically discovered at a somewhat later stage than average. Some imaging procedures, such as Magnetic resonance imaging, MRIs (magnetic resonance imaging), CT scans, ultrasounds and mammography, mammograms with fetal shielding are considered safe during pregnancy; some others, such as Positron emission tomography, PET scans, are not. Treatment is generally the same as for non-pregnant women. However, radiation and radioactive drugs are normally avoided during pregnancy, especially if the fetal dose might exceed 100 cGy. In some cases, some or all treatments are postponed until after birth if the cancer is diagnosed late in the pregnancy. Early deliveries are often used to advance the start of treatment. Surgery is generally safe, but pelvic surgeries during the first trimester may cause miscarriage. Some treatments, especially certain chemotherapy drugs given during the first trimester, increase the risk of birth defects and pregnancy loss (spontaneous abortions and stillbirths). Elective abortions are not required and, for the most common forms and stages of cancer, do not improve the mother's survival. In a few instances, such as advanced uterine cancer, the pregnancy cannot be continued and in others, the patient may end the pregnancy so that she can begin aggressive chemotherapy. Some treatments can interfere with the mother's ability to give birth vaginally or to breastfeed. Cervical cancer may require birth by Caesarean section. Radiation to the breast reduces the ability of that breast to produce milk and increases the risk of mastitis. Also, when chemotherapy is given after birth, many of the drugs appear in breast milk, which could harm the baby.Other animals
Veterinary oncology, concentrating mainly on cats and dogs, is a growing specialty in wealthy countries and the major forms of human treatment such as surgery and radiotherapy may be offered. The most common types of cancer differ, but the cancer burden seems at least as high in pets as in humans. Animals, typically rodents, are often used in cancer research and studies of natural cancers in larger animals may benefit research into human cancer. Across wild animals, there is still limited data on cancer. Nonetheless, a study published in 2022, explored cancer risk in (non-domesticated) zoo mammals, belonging to 191 species, 110,148 individual, demonstrated that cancer is a ubiquitous disease of mammals and it can emerge anywhere along the mammalian phylogeny. This research also highlighted that cancer risk is not uniformly distributed along mammals. For instance, species in the order Carnivora are particularly prone to be affected by cancer (e.g. over 25% of clouded leopards, bat-eared foxes and red wolves die of cancer), while ungulates (especially even-toed ungulates) appear to face consistently low cancer risks. In non-humans, a few types of transmissible cancer have also been described, wherein the cancer spreads between animals by transmission of the tumor cells themselves. This phenomenon is seen in dogs with Sticker's sarcoma (also known as canine transmissible venereal tumor), and in Tasmanian devils with devil facial tumour disease (DFTD).References
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