cancer

2011-01-14T04:06:00.000-08:00

Cancer

Cancer (medical term: malignant neoplasm) is a class of disease in which a group of cells

display uncontrolled growth through division beyond normal limits, invasion that intrudes upon

and destroys adjacent tissues, and sometimes metastasis, in which cancer cells spread to o-

ther locations in the body vialymph or blood. These three malignant properties of cancers differ-

entiate them from benign tumors, which are self-limited, and do not invade or metastasize.

Cancers are primarily an environmental disease with 90-95% of cases due environmental factors

such as lifestyle, and 5-10% directly due to heredity.^[1] Common environmental factors leading

to cancer include: tobacco (25-30%), diet and obesity (30-35%), infections (15-20%), radiation,

stress, lack of physical activity, and environmental pollutants.^[1] These environmental factors ca-

use or enhance abnormalities in the genetic material of cells.^[2] Cell reproduction is an extremely

complex process, which is normally tightly regulated by several classes of genes including onco-

genes and tumor suppressor genes. Hereditary or acquired abnormalities in these regulatory ge-

nes can lead to uncontrolled cell growth, and the development of cancer.

The presence of cancer can be suspected on the basis of symptoms, or findings on radiology. De-
finitive diagnosis of cancer, however, requires the microscopic examination of a biopsy specimen.
Most cancers can be treated. Possible treatments include chemotherapy, radiotherapy and sur-
gery. The prognosis is influenced by the type of cancer and the extent of disease. While cancer
can affect people of all ages the risk typically increases with age.^[3] In 2007 cancer caused about
13% of all human deaths worldwide (7.9 million) and it is projected to be 12 million deaths per
year by 2030.

Cancer
Classification and external resources
A coronal CT scan showing a cancer of rightpleural membranes, the outer surface of the lung and inner surface of the chest wall,malignant mesothelioma. Legend: → tumor ←, ★ central pleural effusion, 1 & 3 lungs, 2 spine, 4 ribs, 5 aorta, 6 spleen, 7 & 8 kidneys, 9 liver.
ICD-10	D 00.
ICD-9	140—239
DiseasesDB	28843
MedlinePlus	001289
MeSH	D009369

Classification

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

Carcinoma: Cancer derived from epithelial cells.

Sarcoma: Cancer derived from connective tissue, or mesenchymal cells.

Lymphoma and leukemia: Cancer derived from hematopoietic (blood-forming) cells

Germ cell tumor: Cancer derived from pluripotent cells.

Blastoma: Cancer derived from immature "precursor" or embryonic tissue.

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, a cancer of the liver is calledhepatocarcin-
oma; a cancer of 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 tha-
t 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 also use the
-oma suffix, examples including melanoma and seminoma.

Signs and symptoms

Local symptoms are lead to the growth ofhemorrhage (bleeding from the skin, mouth or anus)

,ulceration andpain. Although local pain commonly occurs in advanced cancer, the initial swelling

is often painless.None of these are diagnostic, as many of these symptoms commonly occur

in patients who do not have cancer.

Pathophysiology

The affected genes are divided into two broad categories. Oncogenes are genes which promote cell

growthCancer is fundamentally a disease of failure of regulation of tissue growth. In order for a normal cell to

transform into a cancer cell, the genes which regulate cell growth and differentiation must be altered.^[5]

transformation can occur through the formation of novel oncogenes, the inappropriate over-expression of

and reproduction. Tumor suppressor genes are genes which inhibit cell division and survival. Malignant

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.^[6]

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 aremutations - 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'scoding 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 orretrovirus, 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 pres-

ence of disruptive substances called carcinogens, repeated physical injury, heat, ionising radiation, or hypoxia^[7]

(see causes, below).

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

1.>A mutation in the error-correcting machinery of a cell might cause that cell and its children to accumulate

errors more rapidly.

2.>A further mutation in an oncogene might cause the cell to reproduce more rapidly and more frequently than

its normal counterparts.

3.>A further mutation may cause loss of a tumour suppressor gene, disrupting the apoptosis signalling pathway

and resulting in the cell becoming immortal.

4.>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

ognoing process, termed clonal evolution drives progression towards more invasive stages.^[8]

Causes

Cancers are primarily an environmental disease with 90-95% of cases due to environmental factors and 5-10% due

to genetics.^[1] "Environmental", as used by cancer researchers, means any cause that is not genetic, and inclu-

des everything from natural sunlight to industrial pollution to viruses to behavioral choices to old age. Most environ-

mental causes, such as naturally occurringbackground radiation, are not modifiable or controllable. Common env-

ironmental factors that lead to cancer death include: tobacco (25-30% of deaths), diet and obesity (30-35%), infec-

tions (15-20%), radiation, stress, lack of physical activity, and environmental pollutants.^[1]

Chemicals

Further information: Carcinogen

Many mutagens are also carcinogens, but some carcinogens are not mutagens. Alcohol is an example of a 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,^[9] and causes 90% of lung cancer.^[10] Prolonged exposure to asbestos fibers is associated with

mesothelioma.^[11]^[12]

chemical carcinogen that is not a mutagen.^[13] Such chemicals may promote cancers through stimulating the

rate of cell division. Faster rates of replication leaves less time for repair enzymes to repair damaged DNA

duringDNA replication, increasing the likelihood of a mutation.

Decades of research has demonstrated the link between tobacco use and cancer in the lung, larynx, head,

neck, stomach, bladder, kidney, oesophagus and pancreas.^[14]Tobacco smoke contains over fifty known

carcinogens, including nitrosamines and polycyclic aromatic hydrocarbons.^[15] Tobacco is responsible for

about one in three of all cancer deaths in the developed world,^[9] and about one in five worldwide.^[15] Indeed,

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^[when?], decreases in smoking

followed by decreases in lung cancer death rates in men. However, the numbers of smokers worldwide is

still rising, leading to what some organizations have described as the tobacco epidemic.^[16]

Cancer related to ones occupation is believed to represent between 2-20% of all cases.^[17] Every year, at

least 200,000 people die worldwide from cancer related to their workplace.^[18] Millions of workers run the

risk of developing cancers such as lung cancer and mesothelioma from inhaling asbestos fibers and tobacco

smoke, or leukemiafrom exposure to benzene at their workplaces.^[18] Currently, most cancer deaths caused

by occupational risk factors occur in the developed world.^[18] 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.^[19]

Radiation

Sources of ionizing radiation, such as radon gas, can cause cancer. Prolonged exposure to ultraviolet

radiation from the sun can lead to melanoma and other skin malignancies.^[20] 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.^[21] It is estimated that 0.4% of current cancers 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 2007 rates of CT usage.^[22]

Non-ionizing radio frequency radiation from mobile phones and other similar RF sources has also been

proposed as a cause of cancer, but there is currently little established evidence of such a link.^[23]

Infection

Some cancers can be caused by infection.^[24] This is especially true in animals such as birds, but also

in humans, with oncoviruses responsible for up to 20% of human cancers worldwide.^[25] These include

human papillomavirus (cervical carcinoma), Epstein-Barr virus (B-cell lymphoproliferative disease and

nasopharyngeal carcinoma), Kaposi's sarcoma herpesvirus (Kaposi's Sarcoma and primary effusion lym-

phomas),hepatitis B and hepatitis C viruses (hepatocellular carcinoma), and Human T-cell leukemia virus-1

(T-cell leukemias). Bacterial infection may also increase the risk of cancer, as seen in Helicobacter pylori

inducedgastric carcinoma.^[25] Parasitic infections strongly associated with cancer include Schistosoma

haematobium (squamous cell carcinoma of the bladder) and the liver flukes, Opisthorchis viverrini and

Clonorchis sinensis (cholangiocarcinoma).^[26]

Experimental and epidemiological data imply a causative role for viruses and they appear to be the second

most important risk factor for cancer development in humans, exceeded only by tobacco usage.^[27] The

mode of virally induced tumors can be divided into two, acutely transforming or slowly transforming. In acutely

transforming viruses, the virus carries an overactive oncogene called viral-oncogene (v-onc), and the infected

cell is transformed as soon as v-onc is expressed. In contrast, in slowly transforming viruses, the virus

genome is inserted near a proto-oncogene in the host genome. The viral promoter or other transcription

regulation elements then cause overexpression of that proto-oncogene. This induces uncontrolled cell division.

Because the site of insertion is not specific to proto-oncogenes and the chance of insertion near any proto

-oncogene is low, slowly transforming viruses will cause tumors much longer after infection than the acutely

transforming viruses.

Hepatitis viruses, including hepatitis B and hepatitis C, can induce a chronic viral infection that leads to live-

r cancer in 0.47% of hepatitis B patients per year (especially in Asia, less so in North America), and in 1.4%

of hepatitis C carriers per year. Liver cirrhosis, whether from chronic viral hepatitis infection or alcoholism, is

associated with the development of liver cancer, and the combination of cirrhosis and viral hepatitis presents

the highest risk of liver cancer development. Worldwide, liver cancer is one of the most common, and most

deadly, cancers due to a huge burden of viral hepatitis transmission and disease.

Advances in cancer research have made a vaccine designed to prevent cancers available. In 2006, the U.S.

Food and Drug Administration approved a human papilloma virus vaccine, called Gardasil. The vaccine protects

against 6,11,16,18 strains of HPV, which together cause 70% of cervical cancers and 90% of genital warts

. It also lists vaginal and vulvar cancers as being protected. In March 2007, the US Centers for Disease Control

and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) officially recommended that fem-

ales aged 11–12 receive the vaccine, and indicated that females as young as age 9 and as old as age 26 are

also candidates for immunization. There is a second vaccine from Cervarix which protects against the more

dangerous HPV 16,18 strains only. In 2009, Gardasil was approved for protection against genital warts. In 2010

, the Gardasil vaccine was approved for protection against anal cancer for males and reviewers stated there was

no anatomical, histological or physiological anal differences between the genders so females would also be

protected.

In addition to viruses, researchers have noted a connection between bacteria and certain cancers. The most

prominent example is the link between chronic infection of the wall of the stomach with Helicobacter pylori

and gastric cancer.^[28]^[29] Although only a minority of those infected with Helicobacter go on to develop cancer,

since this pathogen is quite common it is probably responsible for most of these cancers.^[30]

HIV is associated with a number of malignancies, including Kaposi's sarcoma, non-Hodgkin's lymphoma, and

HPV-associated malignancies such as anal cancer and cervical cancer. AIDS-defining illnesses have long incl-

uded these diagnoses. The increased incidence of malignancies in HIV patients points to the breakdown of imm-

une surveillance as a possible etiology of cancer.^[31] Certain other immune deficiency states (e.g. common varia-

ble immunodeficiency and IgA deficiency) are also associated with increased risk of malignancy.^[32]

Heredity

Most forms of cancer are sporadic, meaning that there is no inherited cause of the cancer. There are, however, a

number of recognised syndromes where there is an inherited predisposition to cancer, often due to a defect in a

gene that protects against tumor formation. Famous examples are:

1.>certain inherited mutations in the genes BRCA1 and BRCA2 are associated with an elevated risk of breast

cancer and ovarian cancer

3.>tumors of various endocrine organs in multiple endocrine neoplasia (MEN types 1, 2a, 2b)

Li-Fraumeni syndrome (various tumors such as osteosarcoma, breast cancer, soft tissue sarcoma, brain

tumors) due to mutations of p53

4.>Turcot syndrome (brain tumors and colonic polyposis)

5.> Familial adenomatous polyposis an inherited mutation of the APC gene that leads to early onset of colon

carcinoma.

6.>Hereditary nonpolyposis colorectal cancer (HNPCC, also known as Lynch syndrome) can include familial

cases of colon cancer, uterine cancer, gastric cancer, and ovarian cancer, without a preponderance of

colon.

7.> Retinoblastoma, when occurring in young children, is due to a hereditary mutation in the retinoblastoma

gene.

8.> Down syndrome patients, who have an extra chromosome 21, are known to develop malignancies such

as leukemia and testicular cancer, though the reasons for this difference are not well understood.

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 byMHC in-

compatibility.^[33] In humans and other vertebrates, the immune system uses MHC antigens to differentiate bet-

ween "self" and "non-self" cells because these antigens are different from person to person. When non-self anti-

gens are encountered, the immune system reacts against the appropriate cell. Such reactions may protect aga-

inst 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 leukaemia, lymphoma, melanom

a and carcinoma from mother to fetus has been observed.^[33] 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.^[34] though other cases exist^[35] In fact, cancer from

one organism will usually grow in another organism of that species, as long as they share the same histocomp-

atibility genes,^[36] proven using mice; however this would never happen in a real-world setting except as described

above.

In non-humans, a few types of transmissible cancer have been described, wherein the cancer spreads between an-

imals by transmission of the tumor cells themselves. This phenomenon is seen in dogs withSticker's sarcoma, a-

lso known as canine transmissible venereal tumor,^[37] as well as Devil facial tumour disease in Tasmanian devils.

Diagnosis

of these lead to a definitive diagnosis, which usually requires the opinion of a pathologist, a type of physician

(medical doctor) who specializes in the diagnosis of cancer and other diseases. People with suspected cancer

are investigated with medical tests. These commonly include blood tests, X-rays, CT scans and endoscopy.

Most cancers are initially recognized either because signs or symptoms appear or through screening. Neither

Pathology

A cancer may be suspected for a variety of reasons, but the definitive diagnosis of most malignancies must be

confirmed by histological examination of the cancerous cells by a pathologist. Tissue can be obtained from a

biopsy or surgery. Many biopsies (such as those of the skin, breast or liver) can be done in a doctor's office.

Biopsies of other organs are performed under anesthesia and require surgery in an operating room.

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 othe-

r 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 in the surrounding yellow fatty tissue.

An invasive colorectal carcinoma (top center) in acolectomy specimen.

A squamous cell carcinoma (the whitish tumor) near the bronchi in a lung specimen.

A large invasive ductal carcinoma in amastectomy specimen.

Prevention

Cancer prevention is defined as active measures to decrease the incidence of cancer.^[38] The vast majority of

cancer risk factors are environmental or lifestyle-related, thus cancer is largely a preventable disease.^[39]Greate-

r than 30% of cancer is preventable via avoiding risk factors including: tobacco, overweight or obesity, low fruit and

vegetable intake, physical inactivity, alcohol, sexually transmitted infection, air pollution.^[40]

Examples of modifiable cancer risk factors include alcohol consumption (associated with increased risk of oral,

esophageal, breast, and other cancers), smoking (80% of women with lung cancer have smoked in the past, and

90% of men^[41]), physical inactivity (associated with increased risk of colon, breast, and possibly other cancers),

and being overweight / obese (associated with colon, breast, endometrial, and possibly other cancers). Based on

epidemiologic evidence, it is now thought that avoiding excessive alcohol consumption may contribute to reduc-

tions in risk of certain cancers; however, compared with tobacco exposure, the magnitude of effect is modest or

small and the strength of evidence is often weaker. Other lifestyle and environmental factors known to affect can-

cer risk (either beneficially or detrimentally) include certain sexually transmitted diseases (such as those conveyed

by the human papillomavirus), the use of exogenous hormones, exposure to ionizing radiation and ultraviolet radi-

ation from the sun or from tanning beds, and certain occupational and chemical exposures.

Diet and obesity

Main article: Diet and cancer

Medication

The concept that medications could be used to prevent cancer is an attractive one, and many

high-quality clinical trials support the use of such chemoprevention in defined circumstances.

Aspirin has been found to reduce the risk of death from cancer.^[66]

Daily use of tamoxifen, a selective estrogen receptor modulator (SERM), typically for 5 years, has

been demonstrated to reduce the risk of developing breast cancer in high-risk women by about 50%

Raloxifenealso a SERM; has been shown to reduce the risk of breast cancer in high-risk women

equally as well as tamoxifen. It had fewer side effects than tamoxifen, though it did permit more DCIS

to form.^[67]

Finasteride, a 5-alpha-reductase inhibitor, has been shown to lower the risk of prostate cancer, though it

seems to mostly prevent low-grade tumors.^[68] The effect of COX-2 inhibitors such as rofecoxib and cele-

coxibupon the risk of colon polyps have been studied in familial adenomatous polyposis patients^[69] and in

the general population.^[70]^[71] In both groups, there were significant reductions in colon polyp incidence, but

this came at the price of increased cardiovascular toxicity.

As of 2010 vitamins have not been found to be effective at preventing cancer,^[72] while low levels of vitamin D

is correlated with increased cancer risk.^[73]^[74] Whether this relationship is causal and vitamin D supplemen-

tation is protective is yet to be determined.^[75] Beta-carotene supplementation has been found to increase

slightly, but not significantly risks of lung cancer.^[76] Folic acid supplementation has not been found effective

in preventing colon cancer and may increase colon polyps.^[77]

Vaccination

Vaccines have been developed to prevent oncogenic infectious agents and therapeutic vaccines are in

development to stimulate an immune response against cancer-specific epitopes.^[78]

Human papillomavirus vaccine (Gardasil and Cervarix) decreases the risk of developing cervical cancer.^[78]

The hepatitis B vaccine prevents infection with hepatitis B virus and thus decreases the risk of liver cancer.^[78]

Screening

Main article: Cancer screening

Cancer screening involves efforts to detect cancer before symptoms appear.^[79] This may involve physical

examination, blood or urine tests, or medical imaging.^[79] As screening tests may have risks these must

be weighted against the benefits of early detection and treatment.^[79] Especially if they are going to be

recommended for large segments of the population.

Recommendations

The U.S. Preventive Services Task Force (USPSTF) strongly recommends cervical cancer screening in those

who are sexually active and have a cervix at least until the age of 65.^[80] They recommendsmammography for

breast cancer screening every two years for those 50–74 years old, however do not recommend either breast

self-examination or clinical breast examination.^[81] Colorectal cancer screening is recommended via fecal occult

blood testing, sigmoidoscopy, or colonoscopy starting at age of 50 until age 75.^[82] There is insufficient evide-

nce to recommend for or against screening for skin cancer,^[83] oral cancer,^[84] lung cancer,^[85] or prostate

cancer in men under 75.^[86] Routine screening is not recommended for bladder cancer,^[87] testicular cancer,^[88]

ovarian cancer,^[89] pancreatic cancer,^[90] or prostate cancer in men over 75.^[86] A 2009 Cochrane review came

to slightly different conclusions with respect to breast cancer screening stating that routine mammography

may do more harm than good.^[91]

Genetic testing

Genetic testing for high-risk individuals is already available for certain cancer-related genetic mutations

Carriers of genetic mutations that increase risk for cancer incidence can undergo enhanced surveillance,

chemoprevention, or risk-reducing surgery. Early identification of inherited genetic risk for cancer, along

with cancer-preventing interventions such as surgery or enhanced surveillance, can be lifesaving for high-

risk individuals.

Gene	Cancer types
BRCA1, BRCA2	Breast, ovarian, pancreatic
MLH1, MSH2, MSH6, PMS1, PMS2	Colon, uterine, small bowel, stomach, urinary tract

Management

Main article: Management of cancer

Many management options for cancer exist including: chemotherapy, radiation therapy, surgery,

immunotherapy, monoclonal antibody therapy and other methods. Which are used depends upon

the location and grade of the tumor and the stage of the disease, as well as the general state of a

person's health. Experimental cancer treatments are also under development.

Complete removal of the cancer without damage to the rest of the body is the goal of treatment.

Sometimes this can be accomplished by surgery, but the propensity of cancers to invade adjacent

tissue or to spread to distant sites by microscopic metastasis often limits its effectiveness. Surgery

often required the removal of a wide surgical margin or a free margin. The width of the free margin

depends on the type of the cancer, the method of removal (CCPDMA, Mohs surgery, POMA, etc.).

The margin can be as little as 1 mm for basal cell cancer using CCPDMA or Mohs surgery, to several

centimeters for aggressive cancers. The effectiveness of chemotherapy is often limited by toxicity to

other tissues in the body. Radiation can also cause damage to normal tissue.

Because cancer is a class of diseases,^[92]^[93] it is unlikely that there will ever be a single "cure for cancer"

any more than there will be a single treatment for all infectious diseases.^[94] Angiogenesis inhibitors were

once thought to have potential as a "silver bullet" treatment applicable to many types of cancer, but this

has not been the case in practice.^[95]

Prognosis

Epidemiology

Main article: Epidemiology of cancer

As of 2004, worldwide cancer caused 13% of all deaths (7.4 million). The leading causes were:

lung cancer (1.3 million deaths/year), stomach cancer (803,000 deaths),colorectal cancer

(639,000 deaths), liver cancer (610,000 deaths), and breast cancer (519,000 deaths).^[97] The

most significant risk factor is age. According to cancer researcher Robert A. Weinberg, "If we

lived long enough, sooner or later we all would get cancer."^[98] Essentially all of the increase in

Cancer rates between ancient times and people who died in England during 1901 and 1905 is due

to increased lifespans.^[98] Since then, some other factors, especially the increased use of tobacco,

have further raised the rates.^[98]

In the United States, cancer is responsible for 25% of all deaths with 30% of these from lung cancer

The most commonly occurring cancer in men is prostate cancer(about 25% of new cases) and in

women is breast cancer (also about 25%). Cancer can occur in children and adolescents, but it is

uncommon (about 150 cases per million in the U.S.), with leukemia the most common.^[99] In the

first year of life the incidence is about 230 cases per million in the U.S., with the most common being

neuroblastoma.^[100]

In the developed world, one in three people will develop cancer during their lifetimes. If all cancer patients

survived and cancer occurred randomly, the lifetime odds of developing a second primary cancer would

be one in nine.^[101] However, cancer survivors have an increased risk of developing a second primary cancer

and the odds are about two in nine.^[101] About half of these second primaries can be attributed to the

normal one-in-nine risk associated with random chance.^[101] The increased risk is believed to be primarily

due to the same risk factors that produced the first cancer (such as the person's genetic profile, alcohol

and tobacco use, obesity, and environmental exposures), and partly due to the treatment for the first cancer,

which typically includes mutagenic chemotherapeutic drugs or radiation.^[101] Cancer survivors may also

be more likely to comply with recommended screening, and thus may be more likely than average to detect

cancers.^[101]

Most common cancers in US males, by occurrence^[99]

in US females, by occurrence^[99]

in US males, by mortality^[99]

in US females, by mortality^[99]

Death rate from malignant cancer per 100,000 inhabitants in 2004.^[96]

no data

≤ 55

55-80

80-105

105-130

130-155

155-180

180-205

205-230

230-255

255-280

280-305

≥ 305

History

Hippocrates (ca. 460 BC – ca. 370 BC) described several kinds of cancers, referring to them with the

Greek word carcinos (crab or crayfish), among others.^[102] 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".^[103] Since it was against Greek tradition to open the body, Hippocra-

tes only described and made drawings of outwardly visible tumors on the skin, nose, and breasts. Treatm-

ent was based on the humor theory of four bodily fluids (black and yellow bile, blood, and phlegm). Accord-

ing to the patient's humor, treatment consisted of diet, blood-letting, and/or laxatives. Through the centuries

it was discovered that cancer could occur anywhere in the body, but humor-theory based treatment remai-

ned popular until the 19th century with the discovery of cells.

Celsus (ca. 25 BC - 50 AD) translated carcinos into the Latin cancer, also meaning crab. Galen (2nd cent-

ury AD) called benign tumours oncos, Greek for swelling, reserving Hippocrates' carcinos for malignant tu-

mours. He later added the suffix -oma, Greek for swelling, giving the name carcinoma.

The oldest known description and surgical treatment of cancer was discovered in Egypt and dates back to

approximately 1600 BC. The Papyrus describes 8 cases of ulcers of the breast that were treated by cauter-

ization, with a tool called "the fire drill." The writing says about the disease, "There is no treatment."^[104]

Another very early surgical treatment for cancer was described in the 1020s by Avicenna (Ibn Sina) in The

Canon of Medicine. He stated that the excision should be radical and that all diseased tissue should be re-

moved, which included the use of amputation or the removal of veins running in the direction of the tumor.

He also recommended the use of cauterization for the area treated if necessary.^[105]

In the 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 conc-

luded that it was contagious.^[106]

The first cause of cancer was identified by British surgeon Percivall Pott, who discovered in 1775 that

cancer of the scrotum was a common disease among chimney sweeps. The work of other individual

physicians led to various insights, but when physicians started working together they could make firmer

conclusions.

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.^[107]

The use of surgery to treat cancer had poor results due to problems with hygiene. The renowned Scottish

surgeon Alexander Monro saw only 2 breast tumor patients out of 60 surviving surgery for two years. In the

19th century, asepsis improved surgical hygiene and as the survival statistics went up, surgical removal

of the tumor became the primary treatment for cancer. With the exception of William Coley who in the late

19th century felt that the rate of cure after surgery had been higher before asepsis (and who injected bact-

eria into tumors with mixed results), cancer treatment became dependent on the individual art of the surgeon

at removing a tumor. During the same period, the idea that the body was made up of various tissues, that in

turn were made up of millions of cells, laid rest the humor-theories about chemical imbalances in the body.

The age of cellular pathology was born.

The genetic basis of cancer was recognised in 1902 by the German zoologist Theodor Boveri, professor of

zoology at Munich and later in Würzburg.^[108] He discovered a method to generate cells with multiple copies

of the centrosome, a structure he discovered and named. He postulated that chromosomes were distinct

and transmitted different inheritance factors. He suggested that mutations of the chromosomes could gene-

rate a cell with unlimited growth potential which could be passed onto its descendants. He proposed the

existence of cell cycle check points, tumour suppressor genes and oncogenes. He speculated that canc-

ers might be caused or promoted by radiation, physical or chemical insults or by pathogenic microorganisms.

When Marie Curie and Pierre Curie discovered radiation at the end of the 19th century, they stumbled upon

the first effective non-surgical cancer treatment. With radiation also came the first signs of multi-disciplinary

approaches to cancer treatment. The surgeon was no longer operating in isolation, but worked together with

hospital radiologists to help patients. The complications in communication this brought, along with the nec-

essity of the patient's treatment in a hospital facility rather than at home, also created a parallel process of

compiling patient data into hospital files, which in turn led to the first statistical patient studies.

A founding paper of cancer epidemiology was the work of Janet Lane-Claypon, who published a comparative

study in 1926 of 500 breast cancer cases and 500 control patients of the same background and lifestyle

for the British Ministry of Health. Her ground-breaking work on cancer epidemiology was carried on by Ric-

hard Doll andAustin Bradford Hill, who published "Lung Cancer and Other Causes of Death In Relation to

Smoking. A Second Report on the Mortality of British Doctors" followed in 1956 (otherwise known as the

British doctors study). Richard Doll left the London Medical Research Center (MRC), to start the Oxford

unit for Cancer epidemiology in 1968. With the use of computers, the unit was the first to compile large

amounts of cancer data. Modern epidemiological methods are closely linked to current concepts of disease

and public health policy. Over the past 50 years, great efforts have been spent on gathering data across

medical practise, hospital, provincial, state, and even country boundaries to study the interdependence of

environmental and cultural factors on cancer incidence.

Cancer patient treatment and studies were restricted to individual physicians' practices until World War II

,when medical research centers discovered that there were large international differences in disease inci-

dence. This insight drove national public health bodies to make it possible to compile health data across

practises and hospitals, a process that many countries do today. The Japanese medical community obse-

rved that the bone marrow of victims of the atomic bombings of Hiroshima and Nagasakiwas completely

destroyed. They concluded that diseased bone marrow could also be destroyed with radiation, and this

led to the discovery of bone marrow transplants forleukemia. Since World War II, trends in cancer treatme-

nt are to improve on a micro-level the existing treatment methods, standardize them, and globalize them to

find cures through epidemiology and international partnerships.

Engraving with two views of a Dutch woman who had a tumor removed from her neck in 1689.

1938 poster identifying surgery, x-rays and radium as the proper treatments for cancer.

Society and culture

While some diseases (such as heart failure) may have a worse prognosis than certain types of cancer,

it is the subject of widespread fear and taboos. For instance, many will avoid using the word directly and

resort to euphemisms such as "big C".^{[citation needed]}

In Western culture, cancer is regarded as a disease that must be "fought" (see below on Richard Nixon's

"War on Cancer", announced in 1971). On an individual level, there is a widespread perception that peop-

le with cancer who remain optimistic can expect a better prognosis. A 2007 study indicated that this beli-

ef is probably incorrect.^[109]

Research

Main article: Cancer research

Cancer research is the intense scientific effort to understand disease processes and discover possible

therapies.

Research about cancer causes focusses on the following issues:

1.> Agents (e.g. viruses) and events (e.g. mutations) which cause or facilitate genetic changes in cells

destined to become cancer.

2.>The precise nature of the genetic damage, and the genes which are affected by it.

3.>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, effective treatments for cancer since President Nixon declared "War on Cancer" in 1971.

Since 1971 the United States has invested over $200 billion on cancer research; that total includes money

invested by public and private sectors and foundations.^[110] Despite this substantial investment, 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.^[111]

Leading cancer research organizations and projects include the American Association for Cancer Research,

the American Cancer Society (ACS), the American Society of Clinical Oncology, the European Organisation

for Research and Treatment of Cancer, the National Cancer Institute, the National Comprehensive Cancer

Network, and The Cancer Genome Atlas project at the NCI.

Cancer can be devided into three groups:-

1.>Metastatic symptoms: are due to the spread of cancer to other locations in the body.

2.>Systemic symptoms: occur due to distant effects of the cancer that are not related to direct

or metastatic lymph nodes (which can be felt or sometimes seen under the skin), hepatomegaly

(enlarged liver) or splenomegaly.

(enlarged spleen) which can be felt in the abdomen, pain or fracture of affected bones, and neurologicalsymptoms.

spread. Some of these effects can include weight loss (poor appetite and cachexia), fatigue, excessive sweating

(especially night sweats), anemia (low blood count) and other specific conditions termed paraneoplastic phenom-

ena. These may be mediated by immunological or hormonal signals from the cancer cells.