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Cancer is a group of diseases involving abnormal cell growth with the potential to invade or
spread Spread may refer to: Places * Spread, West Virginia Arts, entertainment, and media * ''Spread'' (film), a 2009 film. * ''$pread'', a quarterly magazine by and for sex workers * "Spread", a song by OutKast from their 2003 album ''Speakerboxxx/T ...
to other parts of the body. These contrast with
benign tumor A benign tumor is a mass of cells (tumor) that does not invade neighboring tissue or metastasize (spread throughout the body). Compared to malignant (cancerous) tumors, benign tumors generally have a slower growth rate. Benign tumors have re ...
s, which do not spread. Possible signs and symptoms include a lump, abnormal bleeding, prolonged cough, unexplained
weight loss Weight loss, in the context of medicine, health, or physical fitness, refers to a reduction of the total body mass, by a mean loss of fluid, body fat ( adipose tissue), or lean mass (namely bone mineral deposits, muscle, tendon, and other co ...
, and a change in
bowel movements Defecation (or defaecation) follows digestion, and is a necessary process by which organisms eliminate a solid, semisolid, or liquid waste material known as feces from the digestive tract via the anus. The act has a variety of names ranging f ...
. While these symptoms may indicate cancer, they can also have other causes. Over 100 types of cancers affect humans.
Tobacco use Tobacco smoking is the practice of burning tobacco and ingesting the resulting smoke. The smoke may be inhaled, as is done with cigarettes, or simply released from the mouth, as is generally done with pipes and cigars. The practice is believed ...
is the cause of about 22% of cancer deaths. Another 10% are due to
obesity Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's ...
, poor
diet Diet may refer to: Food * Diet (nutrition), the sum of the food consumed by an organism or group * Dieting, the deliberate selection of food to control body weight or nutrient intake ** Diet food, foods that aid in creating a diet for weight loss ...
, lack of physical activity or excessive drinking of alcohol. Other factors include certain infections, exposure to ionizing radiation, and environmental pollutants. In the developing world, 15% of cancers are due to infections such as ''
Helicobacter pylori ''Helicobacter pylori'', previously known as ''Campylobacter pylori'', is a gram-negative, microaerophilic, spiral (helical) bacterium usually found in the stomach. Its helical shape (from which the genus name, helicobacter, derives) is thoug ...
'',
hepatitis B Hepatitis B is an infectious disease caused by the '' Hepatitis B virus'' (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection. Many people have no symptoms during an initial infection. ...
, hepatitis C,
human papillomavirus infection Human papillomavirus infection (HPV infection) is caused by a DNA virus from the ''Papillomaviridae'' family. Many HPV infections cause no symptoms and 90% resolve spontaneously within two years. In some cases, an HPV infection persists and res ...
,
Epstein–Barr virus The Epstein–Barr virus (EBV), formally called ''Human gammaherpesvirus 4'', is one of the nine known human herpesvirus types in the herpes family, and is one of the most common viruses in humans. EBV is a double-stranded DNA virus. It is b ...
and
human immunodeficiency virus The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immun ...
(HIV). These factors act, at least partly, by changing the
gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
s of a cell. Typically, many genetic changes are required before cancer develops. Approximately 5–10% of cancers are due to inherited genetic defects. 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 A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a dise ...
. The risk of developing certain cancers can be reduced by not smoking, maintaining a healthy weight, limiting alcohol intake, eating plenty of vegetables, fruits, and
whole grain A whole grain is a grain of any cereal and pseudocereal that contains the endosperm, germ, and bran, in contrast to refined grains, which retain only the endosperm. As part of a general healthy diet, consumption of whole grains is associated ...
s, eating
resistant starch Resistant starch (RS) is starch, including its degradation products, that escapes from digestion in the small intestine of healthy individuals. Resistant starch occurs naturally in foods, but it can also be added as part of dried raw foods, or use ...
,
vaccination Vaccination is the administration of a vaccine to help the immune system develop immunity from a disease. Vaccines contain a microorganism or virus in a weakened, live or killed state, or proteins or toxins from the organism. In stimulating ...
against certain infectious diseases, limiting consumption of
processed meat Processed meat is considered to be any meat which has been modified in order to either improve its taste or to extend its shelf life. Methods of meat processing include salting, curing, fermentation, smoking, and/or the addition of chemical pr ...
and
red meat In gastronomy, red meat is commonly red when raw and a dark color after it is cooked, in contrast to white meat, which is pale in color before and after cooking. In culinary terms, only flesh from mammals or fowl (not fish) is classified as ...
, and limiting exposure to direct sunlight. Early detection through screening is useful for
cervical In anatomy, cervical is an adjective that has two meanings: # of or pertaining to any neck. # of or pertaining to the female cervix: i.e., the ''neck'' of the uterus. *Commonly used medical phrases involving the neck are **cervical collar **cerv ...
and colorectal cancer. The benefits of screening for breast cancer are controversial. Cancer is often treated with some combination of
radiation therapy Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radi ...
, surgery,
chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs ( chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemothe ...
and
targeted therapy Targeted therapy or molecularly targeted therapy is one of the major modalities of medical treatment ( pharmacotherapy) for cancer, others being hormonal therapy and cytotoxic chemotherapy. As a form of molecular medicine, targeted therapy blocks ...
. Pain and symptom management are an important part of care.
Palliative care Palliative care (derived from the Latin root , or 'to cloak') is an interdisciplinary medical caregiving approach aimed at optimizing quality of life and mitigating suffering among people with serious, complex, and often terminal illnesses. Wit ...
is particularly important in people 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 The five-year survival rate is a type of survival rate for estimating the prognosis of a particular disease, normally calculated from the point of diagnosis. Lead time bias from earlier diagnosis can affect interpretation of the five-year surviva ...
in the
developed world A developed country (or industrialized country, high-income country, more economically developed country (MEDC), advanced country) is a sovereign state that has a high quality of life, developed economy and advanced technological infrastruct ...
is on average 80%. For cancer in the United States, the average five-year survival rate is 66%. In 2015, about 90.5 million people worldwide had cancer. In 2019, annual cancer cases grew by 23.6 million people and there were 10 million deaths worldwide, representing over the previous decade increases of 26% and 21%, respectively. The most common types of cancer in males are
lung cancer Lung cancer, also known as lung carcinoma (since about 98–99% of all lung cancers are carcinomas), is a malignant lung tumor characterized by uncontrolled cell growth in tissues of the lung. Lung carcinomas derive from transformed, malign ...
, prostate cancer, colorectal cancer, and stomach cancer. In females, the most common types are
breast cancer Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a r ...
, colorectal cancer,
lung cancer Lung cancer, also known as lung carcinoma (since about 98–99% of all lung cancers are carcinomas), is a malignant lung tumor characterized by uncontrolled cell growth in tissues of the lung. Lung carcinomas derive from transformed, malign ...
, and cervical cancer. If
skin cancer Skin cancers are cancers that arise from the skin. They are due to the development of abnormal cells that have the ability to invade or spread to other parts of the body. There are three main types of skin cancers: basal-cell skin cancer (BCC) ...
other than melanoma were included in total new cancer cases each year, it would account for around 40% of cases. In children, acute lymphoblastic leukemia and brain tumors are most common, except in Africa, where
non-Hodgkin lymphoma Non-Hodgkin lymphoma (NHL), also known as non-Hodgkin's lymphoma, is a group of blood cancers that includes all types of lymphomas except Hodgkin lymphomas. Symptoms include enlarged lymph nodes, fever, night sweats, weight loss, and tirednes ...
occurs more often. In 2012, about 165,000 children under 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 global total economic costs of cancer were estimated at US$1.16 trillion per year .


Etymology and definitions

The word comes from the ancient Greek , meaning 'crab' and 'tumor'. Greek physicians
Hippocrates Hippocrates of Kos (; grc-gre, Ἱπποκράτης ὁ Κῷος, Hippokrátēs ho Kôios; ), also known as Hippocrates II, was a Greek physician of the classical period who is considered one of the most outstanding figures in the history o ...
and
Galen Aelius Galenus or Claudius Galenus ( el, Κλαύδιος Γαληνός; September 129 – c. AD 216), often Anglicized as Galen () or Galen of Pergamon, was a Greek physician, surgeon and philosopher in the Roman Empire. Considered to be one ...
, 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 abnormal cell growth with the potential to invade or spread to other parts of the body. They form a subset of
neoplasm A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
s. 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. All tumor cells show the six hallmarks of cancer. These characteristics are required to produce a malignant tumor. They include: * Cell growth and division absent the proper signals * Continuous growth and division even given contrary signals * Avoidance of
programmed cell death Programmed cell death (PCD; sometimes referred to as cellular suicide) is the death of a cell (biology), cell as a result of events inside of a cell, such as apoptosis or autophagy. PCD is carried out in a biological process, which usually confers ...
* Limitless number of cell divisions * Promoting blood vessel construction *
Invasion An invasion is a Offensive (military), military offensive in which large numbers of combatants of one geopolitics, geopolitical Legal entity, entity aggressively enter territory (country subdivision), territory owned by another such entity, gen ...
of tissue and formation of
metastases Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then ...
The progression from normal cells to cells that can form a detectable mass to outright cancer involves multiple steps known as malignant progression.


Signs 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 Specific may refer to: * Specificity (disambiguation) * Specific, a cure or therapy for a specific illness Law * Specific deterrence, focussed on an individual * Specific finding, intermediate verdict used by a jury in determining the fina ...
. 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 A bronchus is a passage or airway in the lower respiratory tract that conducts air into the lungs. The first or primary bronchi pronounced (BRAN-KAI) to branch from the trachea at the carina are the right main bronchus and the left main bronchu ...
resulting in cough or
pneumonia Pneumonia is an inflammatory condition of the lung primarily affecting the small air sacs known as alveoli. Symptoms typically include some combination of productive or dry cough, chest pain, fever, and difficulty breathing. The severi ...
; esophageal cancer can cause narrowing of the
esophagus The esophagus ( American English) or oesophagus (British English; both ), non-technically known also as the food pipe or gullet, is an organ in vertebrates through which food passes, aided by peristaltic contractions, from the pharynx to ...
, making it difficult or painful to swallow; and colorectal cancer may lead to narrowing or blockages in the
bowel The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...
, affecting bowel habits. Masses in breasts or testicles may produce observable lumps.
Ulceration An ulcer is a discontinuity or break in a bodily membrane that impedes normal function of the affected organ. According to Robbins's pathology, "ulcer is the breach of the continuity of skin, epithelium or mucous membrane caused by sloughing o ...
can cause bleeding that can lead to symptoms such as
coughing up blood Hemoptysis is the coughing up of blood or blood-stained mucus from the bronchi, larynx, trachea, or lungs. In other words, it is the airway bleeding. This can occur with lung cancer, infections such as tuberculosis, bronchitis, or pneumonia, a ...
(lung cancer),
anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, th ...
or
rectal bleeding Rectal bleeding refers to bleeding in the rectum. There are many causes of rectal hemorrhage, including inflamed hemorrhoids (which are dilated vessels in the perianal fat pads), rectal varices, proctitis (of various causes), stercoral ulcers an ...
(colon cancer),
blood in the urine Hematuria or haematuria is defined as the presence of blood or red blood cells in the urine. “Gross hematuria” occurs when urine appears red, brown, or tea-colored due to the presence of blood. Hematuria may also be subtle and only detectable w ...
(bladder cancer), or
abnormal vaginal bleeding Vaginal bleeding is any expulsion of blood from the vagina. This bleeding may originate from the uterus, vaginal wall, or cervix. Generally, it is either part of a normal menstrual cycle or is caused by hormonal or other problems of the reprod ...
(endometrial or cervical cancer). Although localized pain may occur in advanced cancer, the initial tumor is usually painless. Some cancers can cause a buildup of fluid within the chest or
abdomen The abdomen (colloquially called the belly, tummy, midriff, tucky or stomach) is the part of the body between the thorax (chest) and pelvis, in humans and in other vertebrates. The abdomen is the front part of the abdominal segment of the torso. ...
.Holland Chp. 1


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 Cachexia () is a complex syndrome associated with an underlying illness, causing ongoing muscle loss that is not entirely reversed with nutritional supplementation. A range of diseases can cause cachexia, most commonly cancer, congestive heart f ...
. Some cancers, such as
Hodgkin's disease Hodgkin lymphoma (HL) is a type of lymphoma, in which cancer originates from a specific type of white blood cell called lymphocytes, where multinucleated Reed–Sternberg cells (RS cells) are present in the patient's lymph nodes. The condition wa ...
,
leukemia Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ' ...
s, and
liver The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
or
kidney cancer Kidney cancer, also known as renal cancer, is a group of cancers that starts in the kidney. Symptoms may include blood in the urine, lump in the abdomen, or back pain. Fever, weight loss, and tiredness may also occur. Complications can include spr ...
s, can cause a persistent
fever Fever, also referred to as pyrexia, is defined as having a body temperature, temperature above the human body temperature, normal range due to an increase in the body's temperature Human body temperature#Fever, set point. There is not a single ...
. Some systemic symptoms of cancer are caused by hormones or other molecules produced by the tumor, known as
paraneoplastic syndromes A paraneoplastic syndrome is a syndrome (a set of signs and symptoms) that is the consequence of a tumor in the body (usually a cancerous one), specifically due to the production of chemical signaling molecules (such as hormones or cytokines) by ...
. Common paraneoplastic syndromes include
hypercalcemia Hypercalcemia, also spelled hypercalcaemia, is a high calcium (Ca2+) level in the blood serum. The normal range is 2.1–2.6 mmol/L (8.8–10.7 mg/dL, 4.3–5.2 mEq/L), with levels greater than 2.6 mmol/L defined as hypercalcemi ...
, which can cause altered mental state, constipation and dehydration, or
hyponatremia Hyponatremia or hyponatraemia is a low concentration of sodium in the blood. It is generally defined as a sodium concentration of less than 135 mmol/L (135 mEq/L), with severe hyponatremia being below 120 mEq/L. Symptoms can be abs ...
, which can also cause altered mental status, vomiting, headaches, or seizures.


Metastasis

Metastasis Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...
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 the
lymphatic system The lymphatic system, or lymphoid system, is an organ system in vertebrates that is part of the immune system, and complementary to the circulatory system. It consists of a large network of lymphatic vessels, lymph nodes, lymphatic or lymphoid o ...
or both. The typical steps in metastasis are local
invasion An invasion is a military offensive in which large numbers of combatants of one geopolitical entity aggressively enter territory owned by another such entity, generally with the objective of either: conquering; liberating or re-establishing con ...
,
intravasation Intravasation is the invasion of cancer cells through the basement membrane into a blood or lymphatic vessel. Intravasation is one of several carcinogenic events that initiate the escape of cancerous cells from their primary sites. Other mechanisms ...
into the blood or lymph, circulation through the body,
extravasation __NOTOC__ Extravasation is the leakage of a fluid out of its container into the surrounding area, especially blood or blood cells from vessels. In the case of inflammation, it refers to the movement of white blood cells from the capillaries to the ...
into the new tissue, proliferation and
angiogenesis Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis. Angiogenesis continues the growth of the vasculature by processes of sprouting and splitting ...
. Different types of cancers tend to metastasize to particular organs, but overall the most common places for metastases to occur are the
lung The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of t ...
s,
liver The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
, brain, and the
bone A bone is a Stiffness, rigid Organ (biology), organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red blood cell, red and white blood cells, store minerals, provid ...
s.


Causes

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 A biophysical environment is a biotic and abiotic surrounding of an organism or population, and consequently includes the factors that have an influence in their survival, development, and evolution. A biophysical environment can vary in scale f ...
'' 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 Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's ...
(30–35%), infections (15–20%),
radiation In physics, radiation is the emission or transmission of energy in the form of waves or particles through space or through a material medium. This includes: * ''electromagnetic radiation'', such as radio waves, microwaves, infrared, visi ...
(both ionizing and non-ionizing, up to 10%), lack of
physical activity Physical activity is defined as any voluntary bodily movement produced by skeletal muscles that requires energy expenditure.Global Recommendations on Physical Activity for Health, 2009. World Health Organization. Geneva, Switzerland. Accessed 13/ ...
, and pollution. Psychological stress does not appear to be a risk factor for the onset of cancer, though it may worsen outcomes in those who already have cancer. It is not generally possible to prove what caused a particular cancer because the various causes do not have specific fingerprints. 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, the cancer may have developed for one of those reasons. Excepting the rare transmissions that occur with pregnancies and occasional
organ donors Organ donation is the process when a person allows an organ of their own to be removed and transplanted to another person, legally, either by consent while the donor is alive or dead with the assent of the next of kin. Donation may be for re ...
, cancer is generally not a
transmissible disease In medicine, public health, and biology, transmission is the passing of a pathogen causing communicable disease from an infected host individual or group to a particular individual or group, regardless of whether the other individual was previou ...
, however factors that may have contributed to the development of cancer can be transmissible; such as oncoviruses like
hepatitis B Hepatitis B is an infectious disease caused by the '' Hepatitis B virus'' (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection. Many people have no symptoms during an initial infection. ...
, Epstein-Barr virus and HIV.


Chemicals

Exposure to particular substances have been linked to specific types of cancer. These substances are called ''
carcinogen A carcinogen is any substance, radionuclide, or radiation that promotes carcinogenesis (the formation of cancer). This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Several radioactive substan ...
s''.
Tobacco smoke Tobacco smoke is a sooty aerosol produced by the incomplete combustion of tobacco during the tobacco smoking, smoking of cigarettes and other tobacco products. Temperatures in burning cigarettes range from about 400 °C between puffs to abo ...
, for example, causes 90% of lung cancer. It also causes cancer in the
larynx The larynx (), commonly called the voice box, is an organ in the top of the neck involved in breathing, producing sound and protecting the trachea against food aspiration. The opening of larynx into pharynx known as the laryngeal inlet is about ...
, head, neck, stomach, bladder, kidney,
esophagus The esophagus ( American English) or oesophagus (British English; both ), non-technically known also as the food pipe or gullet, is an organ in vertebrates through which food passes, aided by peristaltic contractions, from the pharynx to ...
and
pancreas The pancreas is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine gland, i.e. it has both an end ...
. Tobacco smoke contains over fifty known carcinogens, including
nitrosamine In organic chemistry, nitrosamines (or more formally ''N''-Nitrosamines) are organic compounds with the chemical structure , where R is usually an alkyl group. They feature a nitroso group () bonded to a deprotonated amine. Most nitrosamines are ...
s and
polycyclic aromatic hydrocarbon A polycyclic aromatic hydrocarbon (PAH) is a class of organic compounds that is composed of multiple aromatic rings. The simplest representative is naphthalene, having two aromatic rings and the three-ring compounds anthracene and phenanthrene. ...
s. Tobacco is responsible for about one in five cancer deaths worldwide and about one in three in the developed world. Lung cancer death rates in the United States have mirrored
smoking Smoking is a practice in which a substance is burned and the resulting smoke is typically breathed in to be tasted and absorbed into the bloodstream. Most commonly, the substance used is the dried leaves of the tobacco plant, which have bee ...
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 cancers in females are attributed to alcohol exposure, especially liver and digestive tract cancers. Cancer from work-related substance exposures may cause between 2 and 20% of cases, causing at least 200,000 deaths. Cancers such as lung cancer and
mesothelioma Mesothelioma is a type of cancer that develops from the thin layer of tissue that covers many of the internal organs (known as the mesothelium). The most common area affected is the lining of the lungs and chest wall. Less commonly the lining ...
can come from inhaling tobacco smoke or
asbestos Asbestos () is a naturally occurring fibrous silicate mineral. There are six types, all of which are composed of long and thin fibrous crystals, each fibre being composed of many microscopic "fibrils" that can be released into the atmosphere b ...
fibers, or
leukemia Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ' ...
from exposure to
benzene Benzene is an organic chemical compound with the molecular formula C6H6. The benzene molecule is composed of six carbon atoms joined in a planar ring with one hydrogen atom attached to each. Because it contains only carbon and hydrogen atoms, ...
. Exposure to
perfluorooctanoic acid Perfluorooctanoic acid (PFOA; conjugate base perfluorooctanoate; also known colloquially as C8, for its 8 carbon chain structure) is a perfluorinated carboxylic acid produced and used worldwide as an industrial surfactant in chemical processes an ...
(PFOA), which is predominantly used in the production of
Teflon Polytetrafluoroethylene (PTFE) is a synthetic fluoropolymer of tetrafluoroethylene that has numerous applications. It is one of the best-known and widely applied PFAS. The commonly known brand name of PTFE-based composition is Teflon by Chemou ...
, is known to cause two kinds of cancer.


Diet and exercise

Diet,
physical inactivity Physical inactivity refers to the lack of moderate-to-vigorous physical activity in a person's lifestyle. It is distinct from sedentary behavior. Health effects The World Health Organization (WHO) has defined physical inactivity as a global public ...
, and
obesity Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's ...
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 higher
body mass index Body mass index (BMI) is a value derived from the mass (weight) and height of a person. The BMI is defined as the body mass divided by the square of the body height, and is expressed in units of kg/m2, resulting from mass in kilograms and he ...
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 the
immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
and
endocrine system The endocrine system is a messenger system comprising feedback loops of the hormones released by internal glands of an organism directly into the circulatory system, regulating distant target organs. In vertebrates, the hypothalamus is the neu ...
. More than half of the effect from the diet is due to
overnutrition Overnutrition (also known as hyperalimentation) is a form of malnutrition in which the intake of nutrients is oversupplied. The amount of nutrients exceeds the amount required for normal growth, development, and metabolism. The term can also ref ...
(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 Stomach cancer, also known as gastric cancer, is a cancer that develops from the lining of the stomach. Most cases of stomach cancers are gastric carcinomas, which can be divided into a number of subtypes, including gastric adenocarcinomas. Lymph ...
.
Aflatoxin B1 Aflatoxin B1 is an aflatoxin produced by ''Aspergillus flavus'' and '' A. parasiticus''. It is a very potent carcinogen with a TD50 3.2 μg/kg/day in rats. This carcinogenic potency varies across species with some, such as rats and monkeys, seem ...
, a frequent food contaminant, causes liver cancer.
Betel nut The betel (''Piper betle'') is a vine of the family Piperaceae, which includes pepper and kava. The betel plant is native to Southeast Asia. It is an evergreen, dioecious perennial, with glossy heart-shaped leaves and white catkins. Betel plan ...
chewing can cause oral cancer. National differences in dietary practices may partly explain differences in cancer incidence. For example,
gastric cancer Stomach cancer, also known as gastric cancer, is a cancer that develops from the lining of the stomach. Most cases of stomach cancers are gastric carcinomas, which can be divided into a number of subtypes, including gastric adenocarcinomas. Lymph ...
is more common in Japan due to its high-salt diet while
colon cancer Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel mo ...
is more common in the United States. Immigrant cancer profiles mirror those of their new country, often within one generation.


Infection

Worldwide approximately 18% of cancer deaths are related to
infectious disease An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dise ...
s. 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 Cancer bacteria are bacteria infectious organisms that are known or suspected to cause cancer. While cancer-associated bacteria have long been considered to be opportunistic (i.e., infecting healthy tissues after cancer has already established i ...
and
parasites Parasitism is a Symbiosis, close relationship between species, where one organism, the parasite, lives on or inside another organism, the Host (biology), host, causing it some harm, and is Adaptation, adapted structurally to this way of lif ...
may also play a role. Oncoviruses (viruses that can cause cancer) include human papillomavirus ( cervical cancer),
Epstein–Barr virus The Epstein–Barr virus (EBV), formally called ''Human gammaherpesvirus 4'', is one of the nine known human herpesvirus types in the herpes family, and is one of the most common viruses in humans. EBV is a double-stranded DNA virus. It is b ...
(B-cell lymphoproliferative disease and nasopharyngeal carcinoma), Kaposi's sarcoma herpesvirus (Kaposi's sarcoma and primary effusion lymphomas),
hepatitis B Hepatitis B is an infectious disease caused by the '' Hepatitis B virus'' (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection. Many people have no symptoms during an initial infection. ...
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 ''Helicobacter pylori'', previously known as ''Campylobacter pylori'', is a gram-negative, microaerophilic, spiral (helical) bacterium usually found in the stomach. Its helical shape (from which the genus name, helicobacter, derives) is thoug ...
''-induced gastric carcinoma. Parasitic infections associated with cancer include ''Schistosoma haematobium'' (Bladder cancer, squamous cell carcinoma of the bladder) and the liver flukes, ''Opisthorchis viverrini'' and ''Clonorchis sinensis'' (cholangiocarcinoma).


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 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 combined with other cancer-causing agents, such as radon plus tobacco smoke. Radiation can cause cancer in most parts of the body, in all animals and at any age. Children 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 cancer Skin cancers are cancers that arise from the skin. They are due to the development of abnormal cells that have the ability to invade or spread to other parts of the body. There are three main types of skin cancers: basal-cell skin cancer (BCC) ...
s, 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 has been described as a possible carcinogen by the World Health Organization's International Agency for Research on Cancer. Evidence, however, has not supported a concern. This includes that studies have not found a consistent link between mobile phone radiation and cancer risk.


Heredity

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 with colorectal cancer, among others. Statistically for cancers causing most mortality, the relative risk of developing colorectal cancer when a first-degree relative (parent, sibling or child) has been diagnosed with it is about 2. The corresponding relative risk is 1.5 for lung cancer, and 1.9 for prostate cancer. For breast cancer, the relative risk is 1.8 with a first-degree relative having developed it at 50 years of age or older, and 3.3 when the relative developed it when being younger than 50 years of age. Taller people have an increased risk of cancer because they have more cells than shorter people. Since height is genetically determined to a large extent, taller people have a heritable increase of cancer risk.


Physical agents

Some substances cause cancer primarily through their physical, rather than chemical, effects. A prominent example of this is prolonged exposure to
asbestos Asbestos () is a naturally occurring fibrous silicate mineral. There are six types, all of which are composed of long and thin fibrous crystals, each fibre being composed of many microscopic "fibrils" that can be released into the atmosphere b ...
, naturally occurring mineral fibers that are a major cause of
mesothelioma Mesothelioma is a type of cancer that develops from the thin layer of tissue that covers many of the internal organs (known as the mesothelium). The most common area affected is the lining of the lungs and chest wall. Less commonly the lining ...
(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 inhalation) and require years of exposure to produce cancer. Physical trauma resulting in cancer is relatively rare. Claims that breaking bones resulted in bone cancer, for example, have not 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. Frequent consumption of scalding hot tea may produce esophageal cancer. Generally, it is believed that cancer arises, or a pre-existing cancer is encouraged, during the process of healing, rather than 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. Chronic inflammation has been hypothesized to directly cause mutation. Inflammation can contribute to proliferation, survival, angiogenesis and migration of cancer cells by influencing the tumor microenvironment. Oncogenes build up an inflammatory pro-tumorigenic microenvironment.


Hormones

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
gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
s 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
carcinogen A carcinogen is any substance, radionuclide, or radiation that promotes carcinogenesis (the formation of cancer). This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Several radioactive substan ...
s, 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 Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...
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 the
lymphatic system The lymphatic system, or lymphoid system, is an organ system in vertebrates that is part of the immune system, and complementary to the circulatory system. It consists of a large network of lymphatic vessels, lymph nodes, lymphatic or lymphoid o ...
or both. The typical steps in metastasis are local
invasion An invasion is a military offensive in which large numbers of combatants of one geopolitical entity aggressively enter territory owned by another such entity, generally with the objective of either: conquering; liberating or re-establishing con ...
,
intravasation Intravasation is the invasion of cancer cells through the basement membrane into a blood or lymphatic vessel. Intravasation is one of several carcinogenic events that initiate the escape of cancerous cells from their primary sites. Other mechanisms ...
into the blood or lymph, circulation through the body,
extravasation __NOTOC__ Extravasation is the leakage of a fluid out of its container into the surrounding area, especially blood or blood cells from vessels. In the case of inflammation, it refers to the movement of white blood cells from the capillaries to the ...
into the new tissue, proliferation and
angiogenesis Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis. Angiogenesis continues the growth of the vasculature by processes of sprouting and splitting ...
. Different types of cancers tend to metastasize to particular organs, but overall the most common places for metastases to occur are the
lung The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of t ...
s,
liver The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
, brain and the
bone A bone is a Stiffness, rigid Organ (biology), organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red blood cell, red and white blood cells, store minerals, provid ...
s.


Metabolism

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 Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ' ...
, 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 The pancreas is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine gland, i.e. it has both an end ...
and Colorectal cancer, colon. * Sarcoma: Cancers arising from connective tissue (i.e.
bone A bone is a Stiffness, rigid Organ (biology), organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red blood cell, red and white blood cells, store minerals, provid ...
, cartilage, fat, nerve), each of which develops from cells originating in mesenchyme, mesenchymal cells outside the bone marrow. * Lymphoma and
leukemia Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ' ...
: 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 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. File:Breast cancer gross appearance.jpg, An invasive ductal carcinoma of the breast (pale area at the center) surrounded by spikes of whitish scar tissue and yellow fatty tissue File:Colon cancer 2.jpg, An invasive colorectal carcinoma (top center) in a colectomy specimen File:Lung cancer.jpg, A squamous-cell carcinoma (the whitish tumor) near the bronchi in a lung specimen File:BreastCancer.jpg, A large invasive Mammary ductal carcinoma, ductal carcinoma in a mastectomy specimen


Prevention

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 Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's ...
, 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 Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's ...
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 Processed meat is considered to be any meat which has been modified in order to either improve its taste or to extend its shelf life. Methods of meat processing include salting, curing, fermentation, smoking, and/or the addition of chemical pr ...
to an increased risk of breast cancer,
colon cancer Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel mo ...
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 Processed meat is considered to be any meat which has been modified in order to either improve its taste or to extend its shelf life. Methods of meat processing include salting, curing, fermentation, smoking, and/or the addition of chemical pr ...
(e.g., bacon, ham, hot dogs, sausages) and, to a lesser degree,
red meat In gastronomy, red meat is commonly red when raw and a dark color after it is cooked, in contrast to white meat, which is pale in color before and after cooking. In culinary terms, only flesh from mammals or fowl (not fish) is classified as ...
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 of colorectal cancer; however, due to 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 inhibitors may decrease the rate of polyp (medicine), polyp formation in people with familial adenomatous polyposis; however, it is associated with the same adverse effects as NSAIDs. Daily use of tamoxifen or raloxifene reduce the risk of breast cancer in high-risk women. The benefit versus harm for 5-alpha-reductase inhibitor such as finasteride is not clear. Vitamin supplementation does not appear to be effective at preventing cancer. While 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. One 2014 review found that supplements had no significant effect on cancer risk. Another 2014 review concluded that vitamin D3 may decrease the risk of death from cancer (one fewer death in 150 people treated over 5 years), but concerns with the quality of the data were noted. Beta-Carotene supplementation increases lung cancer rates in those who are high risk. Folic acid supplementation is not effective in preventing colon cancer and may increase colon polyps. Selenium supplementation has not been shown to reduce the risk of cancer.


Vaccination

Vaccines have been developed that prevent infection by some
carcinogen A carcinogen is any substance, radionuclide, or radiation that promotes carcinogenesis (the formation of cancer). This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Several radioactive substan ...
ic viruses. HPV vaccine, Human papillomavirus vaccine (Gardasil and Cervarix) decrease 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 where resources allow.


Screening

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 or medical imaging. Cancer biomarker, Cancer screening is not available for many types of cancers. Even when tests are available, they may not be recommended for everyone. ''Universal screening'' or ''mass screening'' involves screening everyone.Wilson JMG, Jungner G. (1968
Principles and practice of screening for disease.
Geneva:World Health Organization. Public Health Papers, No. 34.
''Selective screening'' identifies people who are at higher risk, such as people with a family history. Several factors are considered to determine whether the benefits of screening outweigh the risks and the costs of screening. These factors include: * Possible harms from the screening test: for example, X-ray images involve exposure to potentially harmful ionizing radiation * The likelihood of the test correctly identifying cancer * The likelihood that cancer is present: Screening is not normally useful for rare cancers. * Possible harms from follow-up procedures * Whether suitable treatment is available * Whether early detection improves treatment outcomes * Whether cancer will ever need treatment * Whether the test is acceptable to the people: If a screening test is too burdensome (for example, extremely painful), then people will refuse to participate. * Cost


Recommendations


U.S. Preventive Services Task Force

The U.S. Preventive Services Task Force (USPSTF) issues recommendations for various cancers: * Strongly recommends cervical cancer screening in women who are sexually active and have a cervix at least until the age of 65. * Recommend that Americans be screened for colorectal cancer via fecal occult blood testing, sigmoidoscopy, or colonoscopy starting at age 50 until age 75. * Evidence is insufficient to recommend for or against screening for
skin cancer Skin cancers are cancers that arise from the skin. They are due to the development of abnormal cells that have the ability to invade or spread to other parts of the body. There are three main types of skin cancers: basal-cell skin cancer (BCC) ...
, 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. * Recommends mammography for breast cancer screening every two years from ages 50–74, but does not recommend either breast self-examination or Breast cancer screening, clinical breast examination. A 2013 Cochrane review concluded that breast cancer screening by mammography had no effect in reducing mortality because of overdiagnosis and overtreatment.


Japan

Screens for
gastric cancer Stomach cancer, also known as gastric cancer, is a cancer that develops from the lining of the stomach. Most cases of stomach cancers are gastric carcinomas, which can be divided into a number of subtypes, including gastric adenocarcinomas. Lymph ...
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 Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs ( chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemothe ...
,
radiation therapy Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radi ...
, hormonal therapy (oncology), hormonal therapy,
targeted therapy Targeted therapy or molecularly targeted therapy is one of the major modalities of medical treatment ( pharmacotherapy) for cancer, others being hormonal therapy and cytotoxic chemotherapy. As a form of molecular medicine, targeted therapy blocks ...
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, colorectal cancer,
kidney cancer Kidney cancer, also known as renal cancer, is a group of cancers that starts in the kidney. Symptoms may include blood in the urine, lump in the abdomen, or back pain. Fever, weight loss, and tiredness may also occur. Complications can include spr ...
,
leukemia Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ' ...
, liver cancer, lung cancer, lymphoma, pancreatic cancer, prostate cancer,
skin cancer Skin cancers are cancers that arise from the skin. They are due to the development of abnormal cells that have the ability to invade or spread to other parts of the body. There are three main types of skin cancers: basal-cell skin cancer (BCC) ...
, and thyroid cancer as well as other cancer types. The efficacy of chemotherapy depends on the type of cancer and the stage. In combination with surgery, chemotherapy has proven useful in cancer types including breast cancer, colorectal cancer, pancreatic cancer, osteosarcoma, osteogenic sarcoma, testicular cancer, ovarian cancer and certain lung cancers. Chemotherapy is curative for some cancers, such as some leukemias, ineffective in some brain tumors, and needless in others, such as most non-melanoma skin cancers. The effectiveness of chemotherapy is often limited by its toxicity to other tissues in the body. Even when chemotherapy does not provide a permanent cure, it may be useful to reduce symptoms such as pain or to reduce the size of an inoperable tumor in the hope that surgery will become possible in the future.


Radiation

Radiation therapy involves the use of ionizing radiation in an attempt to either cure or improve symptoms. It works by damaging the DNA of cancerous tissue, causing mitotic catastrophe resulting in the death of the cancer cells. To spare normal tissues (such as skin or organs, which radiation must pass through to treat the tumor), shaped radiation beams are aimed from multiple exposure angles to intersect at the tumor, providing a much larger dose there than in the surrounding, healthy tissue. As with chemotherapy, cancers vary in their response to radiation therapy. Radiation therapy is used in about half of cases. The radiation can be either from internal sources (brachytherapy) or external sources. The radiation is most commonly low energy X-rays for treating skin cancers, while higher energy X-rays are used for cancers within the body. Radiation is typically used in addition to surgery and or chemotherapy. For certain types of cancer, such as early head and neck cancer, it may be used alone. For painful bone metastasis, it has been found to be effective in about 70% of patients.Holland Chp. 41


Surgery

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. 40


Palliative care

Palliative care Palliative care (derived from the Latin root , or 'to cloak') is an interdisciplinary medical caregiving approach aimed at optimizing quality of life and mitigating suffering among people with serious, complex, and often terminal illnesses. Wit ...
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 The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
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), colorectal cancer (860,000) stomach cancer (780,000), liver cancer (780,000), and breast cancer (620,000). This makes invasive cancer the leading cause of death in the developed country, developed world and the second leading in the developing country, developing world. Over half of cases occur in the developing world. Deaths from cancer were 5.8 million in 1990. Deaths have been increasing primarily due to longer lifespans and lifestyle changes in the developing world. The most significant risk factor for developing cancer is age. Although it is possible for cancer to strike at any age, most patients with invasive cancer are over 65. According to cancer researcher Robert Weinberg (biologist), Robert A. Weinberg, "If we lived long enough, sooner or later we all would get cancer." Some of the association between aging and cancer is attributed to immunosenescence, errors accumulated in DNA over a lifetime and age-related changes in the
endocrine system The endocrine system is a messenger system comprising feedback loops of the hormones released by internal glands of an organism directly into the circulatory system, regulating distant target organs. In vertebrates, the hypothalamus is the neu ...
. Aging's effect on cancer is complicated by factors such as DNA damage and inflammation promoting it and factors such as vascular aging and endocrine changes inhibiting it. Some slow-growing cancers are particularly common, but often are not fatal. Autopsy studies in Europe and Asia showed that up to 36% of people have undiagnosed and apparently harmless thyroid cancer at the time of their deaths and that 80% of men develop prostate cancer by age 80. As these cancers do not cause the patient's death, identifying them would have represented overdiagnosis rather than useful medical care. The three most common childhood cancers are
leukemia Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ' ...
(34%), brain tumors (23%) and lymphomas (12%). In the United States cancer affects about 1 in 285 children. Rates of childhood cancer increased by 0.6% per year between 1975 and 2002 in the United States and by 1.1% per year between 1978 and 1997 in Europe. Death from childhood cancer decreased by half between 1975 and 2010 in the United States.


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 Hippocrates of Kos (; grc-gre, Ἱπποκράτης ὁ Κῷος, Hippokrátēs ho Kôios; ), also known as Hippocrates II, was a Greek physician of the classical period who is considered one of the most outstanding figures in the history o ...
( – ) 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 Aelius Galenus or Claudius Galenus ( el, Κλαύδιος Γαληνός; September 129 – c. AD 216), often Anglicized as Galen () or Galen of Pergamon, was a Greek physician, surgeon and philosopher in the Roman Empire. Considered to be one ...
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 Aelius Galenus or Claudius Galenus ( el, Κλαύδιος Γαληνός; September 129 – c. AD 216), often Anglicized as Galen () or Galen of Pergamon, was a Greek physician, surgeon and philosopher in the Roman Empire. Considered to be one ...
(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 cancer Skin cancers are cancers that arise from the skin. They are due to the development of abnormal cells that have the ability to invade or spread to other parts of the body. There are three main types of skin cancers: basal-cell skin cancer (BCC) ...
s, 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 disease An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dise ...
s. 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


Further reading

* * * * * *


External links

*
"On telling cancer patients to have a positive attitude"
at ''The Atlantic'' {{Authority control Cancer, Aging-associated diseases Oncology, *Cancer Latin words and phrases Wikipedia medicine articles ready to translate