Cancer

Cancer is a class of diseases characterized by uncontrolled cell division and the ability of these cells to invade other tissues, either by direct growth into adjacent tissue (invasion) or by migration of cells to distant sites (metastasis). This unregulated growth is caused by damage to DNA, resulting in mutations to vital genes that control cell division, among other functions. One or more of these mutations, which can be inherited or acquired, can lead to uncontrolled cell division and tumor formation. Tumor ("swelling" in Latin) refers to any abnormal mass of tissue, but may be either malignant (cancerous) or benign (noncancerous). Only malignant tumors are capable of invading other tissues or metastasizing.

Causes and pathophysiology

Origins of cancer

Cell division (proliferation) is a physiological process that occurs in almost all tissues and under many circumstances. Normally the balance between proliferation and cell death is tightly regulated to ensure the integrity of organs and tissues. Mutations in DNA that lead to cancer disrupt these orderly processes.

Related Topics:
Cell division - Tissues - DNA

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The uncontrolled and often rapid proliferation of cells can lead to either a benign tumor or a malignant tumor (cancer). Benign tumors do not spread to other parts of the body or invade other tissues, and they are rarely a threat to life unless they extrinsically compress vital structures. Malignant tumors can invade other organs, spread to distant locations (metastasize) and become life-threatening.

Related Topics:
Benign - Tumor - Malignant - Metastasize

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Molecular biology

Carcinogenesis (meaning literally, the creation of cancer) is the process of derangement of the rate of cell division due to damage to DNA.

Related Topics:
Carcinogenesis - DNA

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Cancer is, ultimately, a disease of genes. Typically, a series of several mutations is required before a normal cell transforms into a cancer cell. The process involves both proto-oncogenes and tumor suppressor genes. Proto-oncogenes are involved in signal transduction by coding for a chemical "messenger", produced when a cell undergoes protein synthesis. These messengers, send signals based on the amount of them present to the cell or other cells, telling them to undergo mitosis, in order divide and reproduce. When mutated, they become oncogenes and overexpress the signals to divide, and thus cells have a higher chance to divide excessively. Frustratingly, the chance of cancer cannot be reduced by removing proto-oncogenes from the human genome as they are critical for growth, repair and homeostasis of the body. It is only when they become mutated, that the signals for growth become excessive.

Related Topics:
Gene - Mutation - Proto-oncogene - Tumor suppressor gene - Signal transduction - Chemical - Protein synthesis - Mitosis - Oncogene - Overexpress - Homeostasis

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Tumor suppressor genes code for chemical messengers that command cells to slow or stop mitosis in order to allow DNA repair. This is done by special enzymes which detect any mutation or damage to DNA, such that the mistake is not carried on to the next generation. Tumor suppressor genes are usually triggered by signals that DNA damage has occurred. In addition to inhibiting mitosis, they can code for such enzymes themselves, or sending signals to activate such enzymes. However, a mutation can damage the tumor suppressor gene itself, or the signal pathway which activates it, "switching it off". The invariable consequence of this is that DNA repair is hindered or inhibited: DNA damage accumulates without repair, inevitably leading to cancer.

Related Topics:
DNA repair - Enzymes

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In general, mutations in both types of genes are required for cancer to occur. For example, a mutation limited to one oncogene would be suppressed by normal mitosis control (the Knudson or 1-2-hit hypothesis) and tumor suppressor genes. A mutation to only one tumor suppressor gene would not cause cancer either, due to the presence of many "backup" genes that duplicate its functions. It is only when enough proto-oncogenes have mutated into oncogenes, and enough tumor suppressor genes deactivated or damaged, that the signals for cell growth overwhelm the signals to regulate it, that cell growth quickly spirals out of control.

Related Topics:
Knudson - Backup

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Mutations can have various causes. Particular causes have been linked to specific types of cancer. Tobacco smoking is associated with lung cancer. Prolonged exposure to radiation, particularly ultraviolet radiation from the sun, leads to melanoma and other skin malignancies. Breathing asbestos fibers is associated with mesothelioma. In more general terms, chemicals called mutagens and free radicals are known to cause mutations. Other types of mutations can be caused by chronic inflammation, as neutrophil granulocytes secrete free radicals that damage DNA. Chromosomal translocations, such as the Philadelphia chromosome, are a special type of mutation that involve exchanges between different chromosomes.

Related Topics:
Tobacco smoking - Lung cancer - Radiation - Ultraviolet radiation - Sun - Melanoma - Asbestos - Mesothelioma - Mutagen - Free radical - Inflammation - Neutrophil granulocyte - Chromosomal translocation - Philadelphia chromosome

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Many mutagens are also carcinogens, but some carcinogens are not mutagens. Examples of carcinogens that are not mutagens include alcohol and estrogen. These are thought to promote cancers through their stimulating effect on the rate of cell mitosis. Faster rates of mitosis increasingly leave less window space for repair enzymes to repair damaged DNA during DNA replication, increasingly the likelihood of a genetic mistake. A mistake made during mitosis can lead to the daughter cells receiving the wrong number of chromosomes, which leads to aneuploidy and may lead to cancer.

Related Topics:
Mutagen - Carcinogen - Alcohol - Estrogen - Mitosis - DNA replication - Chromosomes - Aneuploidy

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Mutations can also be inherited. Inheriting certain mutations in the BRCA1 gene, a tumor suppressor gene, renders a woman much more likely to develop breast cancer and ovarian cancer. Mutations in the Rb1 gene predispose to retinoblastoma, and those in the APC gene lead to colon cancer.

Related Topics:
BRCA1 - Breast cancer - Ovarian cancer - Rb1 - Retinoblastoma - APC - Colon cancer

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Some types of viruses can cause mutations. They play a role in about 15% of all cancers. Tumor viruses, such as some retroviruses, herpesviruses and papillomaviruses, usually carry an oncogene or a gene inhibits normal tumor suppression in their genome.

Related Topics:
Retrovirus - Herpesvirus - Papillomavirus - Genome

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It is impossible to tell the initial cause for any specific cancer. However, with the help of molecular biological techniques, it is possible to characterize the mutations or chromosomal aberrations within a tumor, and rapid progress is being made in the field of predicting prognosis based on the spectrum of mutations in some cases. For example, up to half of all tumors have a defective p53 gene, a tumor suppressor gene also known as "the guardian of the genome". This mutation is associated with poor prognosis, since those tumor cells are less likely to go into apoptosis (programmed cell death) when damaged by therapy. Telomerase mutations remove additional barriers, extending the number of times a cell can divide. Other mutations enable the tumor to grow new blood vessels to provide more nutrients, or to metastasize, spreading to other parts of the body.

Related Topics:
Molecular biological - Prognosis - P53 - Apoptosis - Telomerase - Grow new blood vessels

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Malignant tumors cells have distinct properties:

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• evading apoptosis
• unlimited growth potential (immortalitization)
• self-sufficiency of growth factors
• insensitivity to anti-growth factors
• increased cell division rate
• altered ability to differentiate
• no ability for contact inhibition
• ability to invade neighbouring tissues
• ability to build metastases at distant sites
• ability to promote blood vessel growth (angiogenesis)

A cell that degenerates into a tumor cell does not usually acquire all these properties at once, but its descendant cells are selected to build them. This process is called clonal evolution. A first step in the development of a tumor cell is usually a small change in the DNA, often a point mutation, which leads to a genetic instability of the cell. The instability can increase to a point where the cell loses whole chromosomes, or has multiple copies of several. Also, the DNA methylation pattern of the cell changes, activating and deactivating genes without the usual control. Cells that divide at a high rate, such as epithelials, show a higher risk of becoming tumor cells than those which divide less, for example neurons.

Related Topics:
Selected - Clonal evolution - Point mutation - Chromosome - DNA methylation - Gene - Epithelial - Neuron

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Morphology

Cancer tissue has a distinctive appearance under the microscope. Among the distinguishing traits are a large number of dividing cells, variation in nuclear size and shape, variation in cell size and shape, loss of specialized cell features, loss of normal tissue organization, and a poorly defined tumor boundary. Immunohistochemistry and other molecular methods may characterise specific markers on tumor cells, which may aid in diagnosis and prognosis.

Related Topics:
Microscope - Nuclear - Immunohistochemistry

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Biopsy and microscopical examination can also distinguish between malignancy and hyperplasia, which refers to tissue growth based on an excessive rate of cell division, leading to a larger than usual number of cells but with a normal orderly arrangement of cells within the tissue. This process is considered reversible. Hyperplasia can be a normal tissue response to an irritating stimulus, for example callus.

Related Topics:
Hyperplasia - Callus

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Dysplasia is an abnormal type of excessive cell proliferation characterized by loss of normal tissue arrangement and cell structure. Often such cells revert back to normal behavior, but occasionally, they gradually become malignant.

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The most severe cases of dysplasia are referred to as "carcinoma in situ." In Latin, the term "in situ" means "in place", so carcinoma in situ refers to an uncontrolled growth of cells that remains in the original location and shows no propensity to invade other tissues. Nevertheless, carcinoma in situ may develop into an invasive malignancy and is usually removed surgically, if possible.

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Heredity

Most forms of cancer are "sporadic", and have no basis in heredity. There are, however, a number of recognised syndromes of cancer with a hereditary component. Examples are:

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• certain inherited mutations in the genes BRCA1 and BRCA2 are associated with an elevated risk of breast cancer and ovarian cancer
• 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
• Turcot syndrome (brain tumors and colonic polyposis)
• Familial adenomatous polyposis an inherited mutation of the APC gene that leads to early onset of colon carcinoma.
• Retinoblastoma in young children is an inherited cancer

Environment and diet

The most consistent finding, over decades of research, is the strong association between tobacco use and cancers of many sites. Hundreds of epidemiological studies have confirmed this association. Further support comes from the fact that 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 followed by decreases in lung cancer death rates in men. Up to half of all cancer cases can be attributed to smoking, diet, and environmental pollution.

Related Topics:
Tobacco - Lung cancer - Smoking

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