Cancer 
i//, known medically as a
malignant neoplasm, is a broad group of diseases involving unregulated cell growth. In cancer,
cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also
spread to more distant parts of the body through the
lymphatic system or
bloodstream. Not all tumors are cancerous;
benign tumors do not invade neighboring tissues and do not spread throughout the body. There are over 200 different known cancers that affect humans.
The causes of cancer are diverse, complex, and only partially understood. Many things are known to increase the risk of cancer, including
tobaccouse,
dietary factors, certain
infections, exposure to
radiation,
lack of physical activity,
obesity, and environmental pollutants.These factors can directly damage genes or combine with existing genetic faults within cells to cause cancerous mutations.Approximately 5–10% of cancers can be traced directly to inherited genetic defects.Many cancers could be prevented by not smoking, eating more vegetables, fruits and whole grains, eating less meat and refined carbohydrates, maintaining a healthy weight, exercising, minimizing sunlight exposure, and being
vaccinated against some infectious diseases.
Cancer can be detected in a number of ways, including the presence of certain
signs and symptoms,
screening tests, or
medical imaging. Once a possible cancer is detected it is diagnosed by
microscopic examination of a
tissue sample. Cancer is usually treated with
chemotherapy,
radiation therapy and
surgery. The chances of surviving the disease vary greatly by the type and location of the cancer and the extent of disease at the start of treatment. While cancer can affect people of all ages, and a few types of cancer are more common in children, the risk of developing cancer generally increases with age. In 2007, cancer caused about 13% of
all human deaths worldwide (7.9 million). Rates are rising as more people live to an old age and as mass lifestyle changes occur in the developing world.
Definitions
There is no one definition that describes all cancers. They are a large family of diseases which form a subset of
neoplasms, which show some features that suggest of
malignancy. A neoplasm or tumor is a group of cells that have undergone unregualated growth, and will often form a mass or lump, but may be distributed diffusely.
Six characteristics of malignancies have been proposed: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis.The progression from normal cells to cells that can form a discernible mass to outright cancer involves multiple steps.
Signs and symptoms
Symptoms of cancer
metastasis depend on the location of the tumor.
When cancer begins it invariably produces no symptoms with signs and symptoms only appearing as the mass continues to grow or
ulcerates. The findings that result depend on the type and location of the cancer. Few symptoms are
specific, with many of them also frequently occurring in individuals who have other conditions. Cancer is the new "
great imitator". Thus it is not uncommon for people diagnosed with cancer to have been treated for other diseases to which it was assumed their symptoms were due.
Local effects
Local symptoms may occur due to the mass of the tumor or its ulceration. For example, mass effects from
lung cancer can cause blockage of the
bronchus resulting in
cough or
pneumonia;
esophageal cancer can cause narrowing of the esophagus, making it difficult or painful to swallow; and
colorectal cancer may lead to narrowing or blockages in the bowel, resulting in changes in bowel habits. Masses in breasts or testicles may be easily felt.
Ulceration can cause bleeding which, if it occurs in the lung, will lead to
coughing up blood, in the bowels to
anemia or
rectal bleeding, in the bladder to blood in the urine, and in the uterus to vaginal bleeding. Although localized pain may occur in advanced cancer, the initial swelling is usually painless. Some cancers can cause build up of fluid within the chest or abdomen.
Systemic symptoms
General symptoms occur due to distant effects of the cancer that are not related to direct or metastatic spread. These may include: unintentional weight loss,
fever, being excessively tired, and changes to the skin.
Hodgkin disease,
leukemias, and cancers of the liver or kidney can cause a persistent
fever of unknown origin.
Metastasis
Symptoms of metastasis are due to the spread of cancer to other locations in the body. They can include enlarged
lymph nodes (which can be felt or sometimes seen under the skin and are typically hard),
hepatomegaly (enlarged liver) or
splenomegaly (enlarged spleen) which can be felt in the
abdomen, pain or
fracture of affected bones, and
neurological symptoms.Most cancer deaths are due to cancer that has spread from its primary site to other organs (metastasized).
Causes
Cancers are primarily an environmental disease with 90–95% of cases attributed to environmental factors and 5–10% due to genetics.
Environmental, as used by cancer researchers, means any cause that is not
inherited genetically, not merely pollution.Common environmental factors that contribute to cancer death include
tobacco (25–30%), diet and
obesity (30–35%),
infections(15–20%),
radiation (both ionizing and non-ionizing, up to 10%), stress, lack of
physical activity, and
environmental pollutants.
It is nearly impossible to prove what caused a cancer in any individual, because most cancers have multiple possible causes. For example, if a person who uses tobacco heavily develops lung cancer, then it was probably caused by the tobacco use, but since everyone has a small chance of developing lung cancer as a result of air pollution or radiation, then there is a small chance that the cancer developed because of air pollution or radiation.
Chemicals
Cancer pathogenesis is traceable back to
DNA mutations that impact cell growth and metastasis. Substances that cause DNA mutations are known as mutagens, and mutagens that cause cancers are known as carcinogens. Particular substances have been linked to specific types of cancer.
Tobacco smoking is associated with many forms of cancer,and causes 90% of
lung cancer.
Many
mutagens are also
carcinogens, but some carcinogens are not mutagens.
Alcohol is an example of a chemical carcinogen that is not a mutagen.In Western Europe 10% of cancers in males and 3% of cancers in females are attributed to alcohol.
Decades of research has demonstrated the link between
tobacco use and cancer in the
lung,
larynx, head, neck, stomach, bladder, kidney,
esophagusand
pancreas.Tobacco smoke contains over fifty known carcinogens, including
nitrosamines and
polycyclic aromatic hydrocarbons.Tobacco is responsible for about one in three of all cancer deaths in the developed world,and about one in five worldwide.
Lung cancer death rates in the United States have mirrored
smoking patterns, with increases in smoking followed by dramatic increases in lung cancer death rates and, more recently, decreases in smoking rates since the 1950s followed by decreases in lung cancer death rates in men since 1990.However, the numbers of smokers worldwide is still rising, leading to what some organizations have described as the
tobacco epidemic.
Cancer related to one's occupation is believed to represent between 2–20% of all cases.Every year, at least 200,000 people die worldwide from cancer related to their workplace.Most cancer deaths caused by occupational risk factors occur in the developed world.It is estimated that approximately 20,000 cancer deaths and 40,000 new cases of cancer each year in the U.S. are attributable to occupation.Millions of workers run the risk of developing cancers such as
lung cancer and
mesothelioma from inhalig
asbestos fibers and tobacco smoke, or
leukemia from exposure to
benzene at their workplaces.
Diet and exercise
Diet,
physical inactivity, and
obesity are related to approximately 30–35% of cancer deaths.In the United States excess body weight is associated with the development of many types of cancer and is a factor in 14–20% of all cancer deaths.ysical inactivity is believed to contribute to cancer risk not only through its effect on body weight but also through negative effects on
immune system and
endocrine system.More than half of the effect from diet is due to
overnutrition rather than from eating too little healthy foods.
Diets that are low in vegetables, fruits and whole grains, and high in processed or red meats are linked with a number of cancers.A high-salt diet is linked to gastric cancer, aflatoxin B1, a frequent food contaminate, with liver cancer, and Betel nut chewing with oral cancer.This may partly explain differences in cancer incidence in different countries. For example, gastric canceris more common in Japan due to its high-salt diet and colon cancer is more common in the United States. Immigrants develop the risk of their new country, often within one generation, suggesting a substantial link between diet and cancer.
Infection
Worldwide approximately 18% of cancer deaths are related to
infectious diseases.This proportion varies in different regions of the world from a high of 25% in Africa to less than 10% in the developed world.
Viruses are the usual infectious agents that cause cancer but
bacteria and
parasites may also have an effect.
Radiation
Sources of ionizing radiation include
medical imaging, and
radon gas. Radiation can cause cancer in most parts of the body, in all animals, and at any age, although radiation-induced solid tumors usually take 10–15 years, and can take up to 40 years, to become clinically manifest, and radiation-induced
leukemias typically require 2–10 years to appear.Some people, such as those with
nevoid basal cell carcinoma syndrome or
retinoblastoma, are more susceptible than average to developing cancer from radiation exposure.Children and adolescents are twice as likely to develop radiation-induced leukemia as adults; radiation exposure before birth has ten times the effect.Ionizing radiation is not a particularly strong mutagen.Residential exposure to radon gas, for example, has similar cancer risks as
passive smoking.Low-dose exposures, such as living near a
nuclear power plant, are generally believed to have no or very little effect on cancer development.Radiation is a more potent source of cancer when it is combined with other cancer-causing agents, such as radon gas exposure plus smoking tobacco.
Unlike chemical or physical triggers for cancer, ionizing radiation hits molecules within cells randomly. If it happens to strike a
chromosome, it can break the chromosome, result in an
abnormal number of chromosomes, inactivate one or more genes in the part of the chromosome that it hit, delete parts of the DNA sequence, cause
chromosome translocations, or cause other types of
chromosome abnormalities.Major damage normally results in the cell dying, but smaller damage may leave a stable, partly functional cell that may be capable of proliferating and developing into cancer, especially if
tumor suppressor genes were damaged by the radiation.Three independent stages appear to be involved in the creation of cancer with ionizing radiation: morphological changes to the cell, acquiring
cellular immortality (losing normal, life-limiting cell regulatory processes), and adaptations that favor formation of a tumor.Even if the radiation particle does not strike the DNA directly, it triggers responses from cells that indirectly increase the likelihood of mutations.
Medical use of ionizing radiation is a 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. One report estimates that approximately 29,000 future cancers could be related to the approximately 70 million
CT scans performed in the US in 2007.It is estimated that 0.4% of cancers in 2007 in the United States are due to CTs performed in the past and that this may increase to as high as 1.5–2% with rates of CT usage during this same time period.
Prolonged exposure to
ultraviolet radiation from the
sun can lead to
melanoma and other skin malignancies.Clear evidence establishes ultraviolet radiation, especially the non-ionizing medium wave
UVB, as the cause of most non-melanoma
skin cancers, which are the most common forms of cancer in the world.
Heredity
Physical agents
Some substances cause cancer primarily through their physical, rather than chemical, effects on cells.
A prominent example of this is prolonged exposure to
asbestos, naturally occurring mineral fibers which are a major cause of
mesothelioma, which is a cancer of the
serous membrane, usually the serous membrane surrounding the lungs.Other substances in this category, including both naturally occurring and synthetic asbestos-like fibers such as
wollastonite,
attapulgite,
glass wool, and
rock wool, are believed to have similar effects.
Usually, physical carcinogens must get inside the body (such as through inhaling tiny pieces) and require years of exposure to develop cancer.
Physical trauma resulting in cancer is relatively rare.Claims that breaking bones resulted in bone cancer, for example, have never been proven.Similarly, physical trauma is not accepted as a cause for cervical cancer, breast cancer, or brain cancer.
One accepted source is frequent, long-term application of hot objects to the body. It is possible that repeated burns on the same part of the body, such as those produced by
kanger and kairo heaters (charcoal
hand warmers), may produce skin cancer, especially if carcinogenic chemicals are also present.Frequently drinking scalding hot tea may produce esophageal cancer.
Generally, it is believed that the cancer arises, or a pre-existing cancer is encouraged, during the process of repairing the trauma, rather than the cancer being caused directly by the trauma.However, repeated injuries to the same tissues might promote excessive cell proliferation, which could then increase the odds of a cancerous mutation. There is no evidence that
inflammationitself causes cancer.
Hormones
Some
hormones play a role in the development of cancer by promoting
cell proliferation.
Insulin-like growth factors and their binding proteins play a key role in cancer cell proliferation, differentiation and apoptosis, suggesting possible involvement in carcinogenesis.
Hormones are important agents in sex-related cancers such as cancer of the breast,
endometrium, prostate, ovary, and
testis, and also of
thyroid cancer and
bone cancer.For example, the daughters of women who have breast cancer have significantly higher levels of
estrogen and
progesterone than the daughters of women without breast cancer. These higher hormone levels may explain why these women have higher risk of breast cancer, even in the absence of a breast-cancer gene.Similarly, men of African ancestry have significantly higher levels of testosterone than men of European ancestry, and have a correspondingly much higher level of prostate cancer.Men of Asian ancestry, with the lowest levels of testosterone-activating
androstanediol glucuronide, have the lowest levels of prostate cancer.
Other factors are also relevant: obese people have higher levels of some hormones associated with cancer and a higher rate of those cancers.Women who take
hormone replacement therapyhave 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.
Other
Excepting the rare transmissions that occur with pregnancies and only a marginal few organ donors, cancer is generally not a
transmissible disease. The main reason for this is tissue graft rejection caused by
MHC incompatibility.In humans and other vertebrates, the immune system uses MHC antigens to differentiate between "self" and "non-self" cells because these antigens are different from person to person. When non-self antigens are encountered, the immune system reacts against the appropriate cell. Such reactions may protect against tumour cell engraftment by eliminating implanted cells. In the United States, approximately 3,500 pregnant women have a malignancy annually, and transplacental transmission of
acute leukemia,
lymphoma,
melanomaand
carcinoma from mother to fetus has been observed.The development of donor-derived tumors from organ transplants is exceedingly rare. The main cause of organ transplant associated tumors seems to be malignant melanoma, that was undetected at the time of organ harvest.Job stress does not appear to be a significant factor at least in lung, colorectal, breast and prostate cancers.
Pathophysiology
Main article:
Carcinogenesis
Cancers are caused by a series of mutations. Each mutation alters the behavior of the cell somewhat.
Genetic alterations
Cancer is fundamentally a disease of tissue growth regulation failure. In order for a normal cell to
transform into a cancer cell, the
genes which regulate cell growth and differentiation must be altered.
The affected genes are divided into two broad categories.
Oncogenes are genes which promote cell growth and reproduction.
Tumor suppressor genes are genes which inhibit cell division and survival. Malignant transformation can occur through the formation of novel oncogenes, the inappropriate over-expression of normal oncogenes, or by the under-expression or disabling of tumor suppressor genes. Typically, changes in
many genes are required to transform a normal cell into a cancer cell.
Genetic changes can occur at different levels and by different mechanisms. The gain or loss of an entire
chromosome can occur through errors in
mitosis. More common are
mutations, which are changes in the
nucleotide sequence of genomic DNA.
Large-scale mutations involve the deletion or gain of a portion of a chromosome.
Genomic amplification occurs when a cell gains many copies (often 20 or more) of a small chromosomal locus, usually containing one or more oncogenes and adjacent genetic material.
Translocation occurs when two separate chromosomal regions become abnormally fused, often at a characteristic location. A well-known example of this is the
Philadelphia chromosome, or translocation of chromosomes 9 and 22, which occurs in
chronic myelogenous leukemia, and results in production of the
BCR-
abl fusion protein, an oncogenic
tyrosine kinase.
Small-scale mutations include point mutations, deletions, and insertions, which may occur in the
promoter region of a gene and affect its
expression, or may occur in the gene's
coding sequence and alter the function or stability of its
protein product. Disruption of a single gene may also result from
integration of genomic material from a
DNA virus or
retrovirus, and resulting in the expression of
viral oncogenes in the affected cell and its descendants.
Replication of the enormous amount of data contained within the DNA of living cells will
probabilistically result in some errors (mutations). Complex error correction and prevention is built into the process, and safeguards the cell against cancer. If significant error occurs, the damaged cell can "self-destruct" through programmed cell death, termed
apoptosis. If the error control processes fail, then the mutations will survive and be passed along to
daughter cells.
Some environments make errors more likely to arise and propagate. Such environments can include the presence of disruptive substances called
carcinogens, repeated physical injury, heat, ionising radiation, or
hypoxia.
The errors which cause cancer are self-amplifying and compounding, for example:
- 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 tumour suppressor gene, disrupting the apoptosis signalling pathway and resulting in the cell becoming immortal.
- A further mutation in signaling machinery of the cell might send error-causing signals to nearby cells.
The transformation of normal cell into cancer is akin to a
chain reaction caused by initial errors, which compound into more severe errors, each progressively allowing the cell to escape the controls that limit normal tissue growth. This rebellion-like scenario becomes an undesirable
survival of the fittest, where the driving forces of
evolution work against the body's design and enforcement of order. Once cancer has begun to develop, this ongoing process, termed
clonal evolution drives progression towards more invasive
stages.
Epigenetic alterations
The central role of DNA damage and epigenetic defects in DNA repair genes in carcinogenesis
Classically, cancer has been viewed as a set of diseases that are driven by progressive genetic abnormalities that include mutations in tumour-suppressor genes and oncogenes, and chromosomal abnormalities. However, it has become apparent that cancer is also driven by
epigenetic alterations.
Epigenetic alterations refer to functionally relevant modifications to the genome that do not involve a change in the nucleotide sequence. Examples of such modifications are changes in
DNA methylation (hypermethylation and hypomethylation) and
histone modification and changes in chromosomal architecture (caused by inappropriate expression of proteins such as
HMGA2 or
HMGA1).Each of these epigenetic alterations serves to regulate gene expression without altering the underlying
DNA sequence. These changes may remain through
cell divisions, last for multiple generations, and can be considered to be epimutations (equivalent to mutations).
Epigenetic alterations occur frequently in cancers. As an example, Schnekenburger and Diederich listed protein coding genes that were frequently altered in their methylation in association with colon cancer. These included 147 hypermethylated and 27 hypomethylated genes. Of the hypermethylated genes, 10 were hypermethylated in 100% of colon cancers, and many others were hypermethylated in more than 50% of colon cancers.
While large numbers of epigenetic alterations are found in cancers, the epigenetic alterations in DNA repair genes, causing reduced expression of DNA repair proteins, may be of particular importance. Such alterations are thought to occur early in progression to cancer and to be a likely cause of the
genetic instability characteristic of cancers.
Reduced expression of DNA repair genes causes deficient DNA repair. This is shown in the figure at the 4th level from the top. (In the figure, red wording indicates the central role of DNA damage and defects in DNA repair in progression to cancer.) When DNA repair is deficient DNA damages remain in cells at a higher than usual level (5th level from the top in figure), and these excess damages cause increased frequencies of mutation and/or epimutation (6th level from top of figure). Mutation rates increase substantially in cells defective in DNA mismatch repair or in homologous recombinational repair (HRR).Chromosomal rearrangements and aneuploidy also increase in HRR defective cells.
Higher levels of DNA damage not only cause increased mutation (right side of figure), but also cause increased epimutation. During repair of DNA double strand breaks, or repair of other DNA damages, incompletely cleared sites of repair can cause epigenetic gene silencing.
Deficient expression of DNA repair proteins due to an inherited mutation can cause increased risk of cancer. Individuals with an inherited impairment in any of 34 DNA repair genes (see article
DNA repair-deficiency disorder) have an increased risk of cancer, with some defects causing up to a 100% lifetime chance of cancer (e.g. p53 mutations).Germ line DNA repair mutations are noted in a box on the left side of the figure, with an arrow indicating their contribution to DNA repair deficiency. However, such germline mutations (which cause highly penetrant cancer syndromes) are the cause of only about 1 percent of cancers.
In sporadic cancers, deficiencies in DNA repair are occasionally caused by a mutation in a DNA repair gene, but are much more frequently caused by epigenetic alterations that reduce or silence expression of DNA repair genes. This is indicated in the figure at the 3rd level from the top. For example, when 113 colorectal cancers were examined in sequence, only four had a
missense mutation in the DNA repair gene
MGMT, while the majority had reduced MGMT expression due to methylation of the MGMT promoter region (an epigenetic alteration).Five different studies found that between 40% and 90% of colorectal cancers have reduced MGMT expression due to methylation of the MGMT promoter region.
Similarly, out of 119 cases of mismatch repair-deficient colorectal cancers that lacked DNA repair gene
PMS2 expression, PMS2 was deficient in 6 due to mutations in the PMS2 gene, while in 103 cases PMS2 expression was deficient because its pairing partner
MLH1 was repressed due to promoter methylation (PMS2 protein is unstable in the absence of MLH1).In the other 10 cases, loss of PMS2 expression was likely due to epigenetic overexpression of the
microRNA,
miR-155, which down-regulates MLH1.
In further examples, tabulated in the article
Epigenetics, epigenetic defects were found at frequencies of between 13%-100% for the DNA repair genes
BRCA1,
WRN,
FANCB,
FANCF, MGMT,
MLH1,
MSH2,
MSH4,
ERCC1, XPF,
NEIL1 and
ATM in cancers including those in breast, ovarian, colorectal, and head and neck. In particular, two or more epigenetic deficiencies in expression of ERCC1, XPF and/or PMS2 occurred simultaneously in the majority of the 49 colon cancers evaluated by Facista et al.
Many studies of heavy metal-induced carcinogenesis show that such heavy metals cause reduction in expression of DNA repair enzymes, some through epigenetic mechanisms. In some cases, DNA repair inhibition is proposed to be a predominant mechanism in heavy metal-induced carcinogenicity. For example, one group of studies shows that arsenic inhibits the DNA repair genes
PARP,
XRCC1,
Ligase III,
Ligase IV,
DNA POLB,
XRCC4,
DNA PKCS,
TOPO2B,
OGG1,
ERCC1,
XPF,
XPB,
XPC,
XPE and
P53.Another group of studies shows that cadmium inhibits the DNA repair genes
MSH2,
ERCC1,
XRCC1,
OGG1,
MSH6,
DNA-PK,
XPD and
XPC.
Cancers usually arise from an assemblage of mutations and epimutations that confer a selective advantage leading to clonal expansion (see
Field defects in progression to cancer). Mutations, however, may not be as frequent in cancers as epigenetic alterations. An average cancer of the breast or colon can have about 60 to 70 protein-altering mutations, of which about 3 or 4 may be “driver” mutations, and the remaining ones may be “passenger” mutations.Colon cancers were also found to have an average of 17 duplicated segments of chromosomes, 28 deleted segments of chromosomes and up to 10 translocations.However, by comparison, epigenetic alterations appear to be more frequent in colon cancers. There are large numbers of hypermethylated genes in colon cancer, as discussed above.
In addition, there are frequent epigenetic alterations of the DNA sequences coding for small RNAs called
microRNAs (or miRNAs). MiRNAs do not code for proteins, but can “target” protein-coding genes and reduce their expression. For instance, epigenetic increase in
CpG island methylation of the DNA sequence encoding miR-137 reduces its expression and is a frequent early epigenetic event in colorectal carcinogenesis, occurring in 81% of colon cancers and in 14% of the normal appearing colonic mucosa adjacent to the cancers. Silencing of miR-137 can affect expression of over 400 genes, the targets of this miRNA.Changes in the level of miR-137 expression cause altered mRNA expression of the target genes by 2 to 20-fold and corresponding, though often smaller, changes in expression of the protein products of the genes. Other microRNAs, with likely comparable numbers of target genes, are even more frequently epigenetically altered in colonic
field defects and in the colon cancers that arise from them. These include miR-124a, miR-34b/c and miR-342 which are silenced by CpG island methylation of their encoding DNA sequences in primary tumors at rates of 99%, 93% and 86%, respectively, and in the adjacent normal appearing mucosa at rates of 59%, 26% and 56%, respectively.Thus, epigenetic alterations are a major source of changes in gene expression, important in cancer.
As pointed out above under genetic alterations, cancer is caused by failure to regulate tissue growth, when the genes which regulate cell growth and differentiation are altered. It has become clear that these alterations are caused by both DNA sequence mutation in
oncogenes and
tumor suppressor genes as well as by epigenetic alterations. The epigenetic deficiencies in expression of DNA repair genes, in particular, likely cause an increased frequency of mutations, some of which then occur in oncogenes and tumor suppressor genes.
Diagnosis
Chest x-ray showing lung cancer in the left lung.
Most cancers are initially recognized either because of the appearance of signs or symptoms or through
screening. Neither of these lead to a definitive diagnosis, which requires the examination of a tissue sample by a
pathologist. People with suspected cancer are investigated with
medical tests. These commonly include
blood tests,
X-rays,
CT scans and
endoscopy.
Most people are distressed to learn that they have cancer. They may become extremely anxious and depressed. The risk of
suicide in people with cancer is approximately double the normal risk.
Classification
Cancers are classified by the
type of cell that the tumor cells resemble and is therefore presumed to be the origin of the tumor. These types include:
- Carcinoma: Cancers derived from epithelial cells. This group includes many of the most common cancers, particularly in the aged, and include nearly all those developing in the breast, prostate, lung, pancreas, and colon.
- Sarcoma: Cancers arising from connective tissue (i.e. bone, cartilage, fat, nerve), each of which develop from cells originating in mesenchymal cells outside the bone marrow.
- Lymphoma and leukemia: These two classes of cancer arise from hematopoietic (blood-forming) cells that leave the marrow and tend to mature in the lymph nodes and blood, respectively. Leukemia is the most common type of cancer in children accounting for about 30%.
- Germ cell tumor: Cancers derived from pluripotent cells, most often presenting in the testicle or the ovary (seminoma and dysgerminoma, respectively).
- Blastoma: Cancers derived from immature "precursor" cells or embryonic tissue. Blastomas are more common in children than in older adults.
Cancers are usually named using
-carcinoma,
-sarcoma or
-blastoma as a suffix, with the Latin or Greek word for the
organ or tissue of origin as the root. For example, cancers of the liver
parenchyma arising from malignant epithelial cells is called
hepatocarcinoma, while a malignancy arising from primitive liver precursor cells is called a
hepatoblastoma, and a cancer arising from fat cells is called a
liposarcoma. For some common cancers, the English organ name is used. For example, the most common type of
breast cancer is called
ductal carcinoma of the breast. Here, the adjective
ductal refers to the appearance of the cancer under the microscope, which suggests that it has originated in the milk ducts.
Benign tumors (which are not cancers) are named using
-oma as a suffix with the organ name as the root. For example, a benign tumor of smooth muscle cells is called a
leiomyoma (the common name of this frequently occurring benign tumor in the uterus is
fibroid). Confusingly, some types of cancer use the
-noma suffix, examples including
melanoma and
seminoma.
Pathology
The tissue
diagnosis given by the pathologist indicates the type of cell that is proliferating, its
histological grade, genetic abnormalities, and other features of the tumor. Together, this information is useful to evaluate the
prognosis of the patient and to choose the best treatment.
Cytogenetics and
immunohistochemistry are other types of testing that the pathologist may perform on the tissue specimen. These tests may provide information about the molecular changes (such as
mutations,
fusion genes, and numerical
chromosome changes) that has happened in the cancer cells, and may thus also indicate the future behavior of the cancer (prognosis) and best treatment.
An invasive
ductal carcinoma of the breast (pale area at the center) surrounded by spikes of whitish scar tissue and yellow fatty tissue.
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Prevention
Cancer prevention is defined as active measures to decrease the risk of cancer.The vast majority of cancer cases are due to environmental risk factors, and many, but not all, of these environmental factors are controllable lifestyle choices. Thus, cancer is considered a largely preventable disease.Greater than 30% of cancer deaths could be prevented by avoiding risk factors including:
tobacco,
overweight /
obesity, an insufficient diet,
physical inactivity,
alcohol,
sexually transmitted infections, and
air pollution.Not all environmental causes are controllable, such as naturally occurring
background radiation, and other cases of cancer are caused through hereditary genetic disorders, and thus it is not possible to prevent all cases of cancer.
Dietary
While many dietary recommendations have been proposed to reduce the risk of cancer, the evidence to support them is not definitive.The primary dietary factors that increase risk are
obesity and
alcohol consumption; with a diet low in fruits and vegetables and high in red meat being implicated but not confirmed.Consumption of
coffee is associated with a reduced risk of
liver cancer.Studies have linked consumption of red or processed meat to an increased risk of breast cancer,
colon cancer, and
pancreatic cancer, a phenomenon which could be due to the presence of carcinogens in meats cooked at high temperatures.Dietary recommendations for cancer prevention typically include an emphasis on vegetables, fruit, whole grains, and fish, and an avoidance of processed and red meat (beef, pork, lamb), animal fats, and refined carbohydrates.
Medication
The concept that medications can be used to prevent cancer is attractive, and evidence supports their use in a few defined circumstances.In the general population
NSAIDs reduce the risk of
colorectal cancer however due to the cardiovascular and gastrointestinal side effects they cause overall harm when used for prevention.
Aspirin has been found to reduce the risk of death from cancer by about 7%.
COX-2 inhibitor may decrease the rate of
polyp formation in people with
familial adenomatous polyposis however are associated with the same adverse effects as NSAIDs.Daily use of
tamoxifen or
raloxifene has been demonstrated to reduce the risk of developing
breast cancer in high-risk women.The benefit verses harm for
5-alpha-reductase inhibitor such as
finasteride is not clear.
Vitamins have not been found to be effective at preventing cancer,although low blood levels of
vitamin D are correlated with increased cancer risk.Whether this relationship is causal and vitamin D supplementation is protective is not determined.
Beta-Carotene supplementation has been found to increase
lung cancer rates in those who are high risk.
Folic acidsupplementation has not been found effective in preventing colon cancer and may increase colon polyps.
Vaccination
Screening
Cancer screening is currently not possible for many types of cancers, and even when tests are available, they may not be recommended for everyone.
Universal screening or
mass screeninginvolves screening everyone.
Selective screening identifies people who are known to be at higher risk of developing cancer, such as people with a family history of cancer.Several factors are considered to determine whether the benefits of screening outweigh the risks and the costs of screening.These factors include:
- 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 of cancer being 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 the cancer will ever need treatment.
- Whether the test is acceptable to the people: If a screening test is too burdensome (for example, being extremely painful), then people will refuse to participate.
- Cost of the test.
Recommendations
Genetic testing
| Gene | Cancer types |
|---|
| BRCA1, BRCA2 | Breast, ovarian, pancreatic |
| HNPCC, MLH1, MSH2, MSH6, PMS1, PMS2 | Colon, uterine, small bowel, stomach, urinary tract |
Genetic testing for individuals at high-risk of certain cancers is recommended.Carriers of these mutations may then undergo enhanced surveillance, chemoprevention, or preventative surgery to reduce their subsequent risk.
Management
Many management options for cancer exist with the primary ones including
surgery,
chemotherapy,
radiation therapy, and
palliative care. Which treatments are used depends upon the type, location and grade of the cancer as well as the person's health and wishes.
Palliative care
Palliative care refers to treatment which attempts to make the patient feel better and may or may not be combined with an attempt to attack the cancer. Palliative care includes action to reduce the physical, emotional, spiritual, and psycho-social distress experienced by people with cancer. Unlike treatment that is aimed at directly killing cancer cells, the primary goal of palliative care is to improve the patient's
quality of life.
Patients at all stages of cancer treatment need some kind of palliative care to comfort them. In some cases,
medical specialty professional organizations recommend that patients and physicians respond to cancer only with palliative care and not with cancer-directed therapy.Those cases have the following characteristics:
- patient has low performance status, corresponding with limited ability to care for oneself
- patient received no benefit from prior evidence-based treatments
- patient is ineligible to participate in any appropriate clinical trial
- the physician sees no strong evidence that treatment would be effective
Palliative care is often confused with
hospice and therefore only involved when people approach
end of life. Like hospice care, palliative care attempts to help the person cope with the immediate needs and to increase the person's comfort. Unlike hospice care, palliative care does not require people to stop treatment aimed at prolonging their lives or curing the cancer.
Multiple national
medical guidelines recommend early palliative care for people whose cancer has produced distressing symptoms (pain, shortness of breath, fatigue, nausea) or who need help coping with their illness. In people who have metastatic disease when first diagnosed, oncologists should consider a palliative care consult immediately. Additionally, an oncologist should consider a palliative care consult in any patient they feel has a prognosis of less than 12 months even if continuing aggressive treatment.
Surgery
Surgery is the primary method of treatment of most isolated solid cancers and may play a role in palliation and prolongation of survival. It is typically an important part of making the definitive diagnosis and staging the tumor as biopsies are usually required. In localized cancer surgery typically attempts to remove the entire mass along with, in certain cases, the
lymph nodes in the area. For some types of cancer this is all that is needed to eliminate the cancer.
Chemotherapy
Radiation
Radiation therapy involves the use of
ionizing radiation in an attempt to either cure or improve the symptoms of cancer. It is used in about half of all cases and the radiation can be from either internal sources in the form of
brachytherapy or external sources. Radiation is typically used in addition to surgery and or chemotherapy but for certain types of cancer such as early
head and neck cancer may be used alone. For painful
bone metastasis it has been found to be effective in about 70% of people.
Alternative treatments
Complementary and alternative cancer treatments are a diverse group of health care systems, practices, and products that are not part of conventional medicine."Complementary medicine" refers to methods and substances used along with conventional medicine, while "alternative medicine" refers to compounds used instead of conventional medicine.Most complementary and alternative medicines for cancer have not been rigorously studied or tested. Some alternative treatments have been investigated and shown to be ineffective but still continue to be marketed and promoted.
Prognosis
Cancer has a reputation as a deadly disease. Taken as a whole, about half of people receiving treatment for invasive cancer (excluding
carcinoma in situ and non-melanoma skin cancers) die from cancer or its treatment.Survival is worse in the developing world.However, the survival rates vary dramatically by type of cancer, with the range running from basically all people surviving to almost no one surviving.
Those who survive cancer are at increased risk of developing a second primary cancer at about twice the rate of those never diagnosed with cancer.The increased risk is believed to be primarily due to the same risk factors that produced the first cancer, partly due to the treatment for the first cancer, and potentially related to better compliance with screening.
Predicting either short-term or long-term survival is difficult and depends on many factors. The most important factors are the particular kind of cancer and the patient's age and overall health. People who are
frail with many other health problems have lower survival rates than otherwise healthy people. A
centenarian is unlikely to survive for five years even if the treatment is successful. People who report a higher quality of life tend to survive longer.People with lower quality of life may be affected by
major depressive disorder and other complications from cancer treatment and/or disease progression that both impairs their quality of life and reduces their quantity of life. Additionally, patients with worse prognoses may be depressed or report a lower quality of life directly because they correctly perceive that their condition is likely to be fatal.
Epidemiology
Death rate from malignant cancer per 100,000 inhabitants in 2004.
[145]
no data
≤ 55
55–80
80–105
105–130
130–155
155–180
|
180–205
205–230
230–255
255–280
280–305
≥ 305
|
Deaths from cancer were 5.8 million in 1990 and rates have been increasing primarily due to an aging population and lifestyle changes in the developing world.The most significant risk factor for developing cancer is old age.Although it is possible for cancer to strike at any age, most people who are diagnosed with invasive cancer are over the age of 65.According to cancer researcher 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.
Some slow-growing cancers are particularly common.
Autopsy studies in Europe and Asia have shown 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 did not cause the person's death, identifying them would have represented
overdiagnosis rather than useful medical care.
The three most common childhood cancers are leukemia (34%), brain tumors (23%), and lymphomas (12%).Rates of childhood cancer have increased by 0.6% per year between 1975 to 2002 in the United States and by 1.1% per year between 1978 and 1997 in Europe.
History
Engraving with two views of a Dutch woman who had a tumor removed from her neck in 1689.
The earliest written record regarding cancer is from 3000 BC in the Egyptian
Edwin Smith Papyrus and describes cancer of the breast.Cancer however has existed for all of human history.
Hippocrates (ca. 460 BC – ca. 370 BC) described several kinds of cancer, referring to them with the
Greek word
καρκίνος karkinos (
crab or
crayfish).This name comes from the appearance of the cut surface of a solid malignant tumour, with "the veins stretched on all sides as the animal the crab has its feet, whence it derives its name".
Galen stated that "cancer of the breast is so called because of the fancied resemblance to a crab given by the lateral prolongations of the tumor and the adjacent distended veins".
:738 Celsus (ca. 25 BC – 50 AD) translated
karkinos into the
Latin cancer, also meaning crab and recommended surgery as treatment.
Galen (2nd century AD) disagreed with the use of surgery and recommended
purgatives instead.These recommendations largely stood for 1000 years.
In the 15th, 16th and 17th centuries, it became more acceptable for doctors to
dissect bodies to discover the cause of death.The German professor
Wilhelm Fabry believed that breast cancer was caused by a milk clot in a mammary duct. The Dutch professor
Francois de la Boe Sylvius, a follower of
Descartes, believed that all disease was the outcome of chemical processes, and that acidic
lymph fluid was the cause of cancer. His contemporary
Nicolaes Tulp believed that cancer was a poison that slowly spreads, and concluded that it was
contagious.
The physician John Hill described tobacco snuff as the cause of nose cancer in 1761.This was followed by the report in 1775 by British surgeon
Percivall Pott that 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
Though 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, "after a long illness" is still commonly used (2012), reflecting an apparent stigma.This deep belief that cancer is necessarily a difficult and usually deadly disease is reflected in the systems chosen by society to compile cancer statistics: the most common form of cancer—non-melanoma skin cancers, accounting for about one-third of all 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.
Cancer is regarded as a disease that must be "fought" to end the "civil insurrection"; a
War on Cancer has been declared. Military metaphors are particularly common in descriptions of cancer's human effects, and they emphasize both the parlous state of the affected individual's health and the need for the individual to take immediate, decisive actions himself, rather than to delay, to ignore, or to rely entirely on others caring for him. The military metaphors also help rationalize radical, destructive treatments.
In the 1970s, a relatively popular
alternative cancer treatment 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 allows society to
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 increases patients' anxiety, as they incorrectly believe that natural emotions of sadness, anger or fear shorten their lives.The idea was excoriated by the notoriously outspoken
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
positive thinking will increase survival.This notion is particularly strong in
breast cancer culture.
In 2007, the overall costs of cancer in the U.S. — including treatment and indirect mortality expenses (such as lost productivity in the workplace) — was estimated to be $226.8 billion. In 2009, 32% of Hispanics and 10% of children 17 years old or younger lacked health insurance; "uninsured patients and those from ethnic minorities are substantially more likely to be diagnosed with cancer at a later stage, when treatment can be more extensive and more costly."
Research
Experimental cancer treatments are treatments that are being studied to see whether they work. Typically, these are studied in
clinical trials to compare the proposed treatment to the best existing treatment. They may be entirely new treatments, or they may be treatments that have been used successfully in one type of cancer, and are now being tested to see whether they are effective in another type.More and more, such treatments are being developed alongside companion diagnostic tests to target the right drugs to the right patients, based on their individual biology.
Cancer research is the intense scientific effort to understand disease processes and discover possible therapies.
Research about cancer causes focuses on the following issues:
- Agents (e.g. viruses) and events (e.g. mutations) which cause or facilitate genetic changes in cells destined to become cancer.
- The precise nature of the genetic damage, and the genes which 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 which lead to further progression of the cancer.
The improved understanding of
molecular biology and
cellular biology due to cancer research has led to a number of new treatments for cancer since U.S. President Nixon declared the "
War on Cancer" in 1971. Since then, the U.S. has spent over $200 billion on cancer research, including resources from the public and private sectors and foundations.During that time, the country has seen a five percent decrease in the cancer death rate (adjusting for size and age of the population) between 1950 and 2005.
Pregnancy
Because cancer is largely a disease of older adults, it is not common in pregnant women. 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 in many pregnant or recently pregnant women. Some imaging procedures, such as
MRIs (magnetic resonance imaging),
CT scans, ultrasounds, and
mammograms with fetal shielding are considered safe during pregnancy; some others, such as
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 to speed the start of treatment are not uncommon. 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 likelihood of the mother surviving or being cured.In a few instances, such as advanced uterine cancer, the pregnancy cannot be continued, and in others, such as an acute leukemia discovered early in pregnancy, the pregnant woman may choose to have abortion so that she can begin aggressive chemotherapy without worrying about birth defects.
Some treatments may interfere with the mother's ability to give birth vaginally or to breastfeed her baby.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 being given after birth, many of the drugs pass through breast milk to the baby, which could harm the baby.
Other animals
Human Iris, Blue type
