Carcinogenesis (meaning literally, the creation of cancer) is the process by which normal cells are transformed into cancer cells. Cancer (medical term Malignant Neoplasm) is a class of Diseases in which a group of cells display uncontrolled The cell is the structural and functional unit of all known living Organisms It is the smallest unit of an organism that is classified as living and is often called
Cell division is a physiological process that occurs in almost all tissues and under many circumstances. Normally, the balance between proliferation and programmed cell death, usually in the form of apoptosis, is maintained by tightly regulating both processes to ensure the integrity of organs and tissues. Mutations in DNA that lead to cancer (only certain mutations can lead to cancer and the majority of potential mutations will have no bearing) disrupt these orderly processes by disrupting the programming regulating the processes.
Carcinogenesis is caused by this mutation of the genetic material of normal cells, which upsets the normal balance between proliferation and cell death. This results in uncontrolled cell division and tumor formation. The uncontrolled and often rapid proliferation of cells can lead to benign tumors; some types of these may turn into malignant tumors (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 compress vital structures or are physiologically active for instance, producing a hormone. Malignant tumors can invade other organs, spread to distant locations (metastasis) and become life threatening. Metastasis ( Greek: displacement μετά=next + στάσις=placement, plural metastases) sometimes abbreviated mets,
More than one mutation is necessary for carcinogenesis. In fact, a series of several mutations to certain classes of genes is usually required before a normal cell will transform into a cancer cell. Only mutations in those certain types of genes which play vital roles in cell division, apoptosis (cell death), and DNA repair will cause a cell to lose control of its cell proliferation.
Contents |
Mechanisms of carcinogenesis
Cancer is, ultimately, a disease of genes. History See also History of genetics The existence of genes was first suggested by Gregor Mendel (1822-1884 who in the 1860s studied inheritance In order for cells to start dividing uncontrollably, genes which regulate cell growth must be damaged. Proto-oncogenes are genes which promote cell growth and mitosis, a process of cell division, and tumor suppressor genes discourage cell growth, or temporarily halts cell division from occurring in order to carry out DNA repair. An oncogene is a protein encoding Gene, which — when deregulated — participates in the onset and development of Cancer. Mitosis is the process in which a Eukaryotic cell separates the Chromosomes in its Cell nucleus, into two identical sets in two daughter nuclei A tumor suppressor gene, or antioncogene is a Gene that protects a cell from one step on the path to cancer DNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its Genome. Typically, a series of several mutations to these genes are required before a normal cell transforms into a cancer cell. In biology mutations are changes to the Nucleotide sequence of the Genetic material of an organism
Proto-oncogenes
Proto-oncogenes promote cell growth in a variety of ways. Many can produce hormones, a "chemical messenger" between cells which encourage mitosis, the effect of which depends on the signal transduction of the receiving tissue or cells. Hormones (from Greek ὁρμή - "impetus" are chemicals released by cells that affect cells in other parts of the body In Biology, signal transduction refers to any process by which a cell converts one kind of signal or stimulus into another Some are responsible for the signal transduction system and signal receptors in cells and tissues themselves, thus controlling the sensitivity to such hormones. In Biochemistry, a receptor is a Protein molecule embedded in either the Plasma membrane or Cytoplasm of a cell to which a mobile signaling They often produce mitogens, or are involved in transcription of DNA in protein synthesis, which create the proteins and enzymes is responsible for producing the products and biochemicals cells use and interact with. A mitogen is a Chemical substance, usually some form of a Protein, that encourages a cell to commence Cell division, triggering Mitosis. Transcription is the synthesis of RNA under the direction of DNA Protein synthesis is the creation of proteins using DNA and' RNA'. Proteins are large Organic compounds made of Amino acids arranged in a linear chain and joined together by Peptide bonds between the Carboxyl Enzymes are Biomolecules that catalyze ( ie increase the rates of Chemical reactions Almost all enzymes are Proteins Biochemistry is the study of the chemical processes in living Organisms It deals with the Structure and function of cellular components such as
Mutations in proto-oncogenes can modify their expression and function, increasing the amount or activity of the product protein. Gene expression is the process by which inheritable information from a Gene, such as the DNA sequence, is made into a functional Gene product, such When this happens, they become oncogenes, and thus cells have a higher chance to divide excessively and uncontrollably. An oncogene is a protein encoding Gene, which — when deregulated — participates in the onset and development of Cancer. The chance of cancer cannot be reduced by removing proto-oncogenes from the genome as they are critical for growth, repair and homeostasis of the body. In classical genetics the genome of a Diploid Organism including Eukarya refers to a full set of chromosomes or genes in a Gamete, thereby Homeostasis (from Greek: ὅμος hómos, "equal" and ιστημι istēmi, "to stand" lit It is only when they become mutated, that the signals for growth become excessive.
Tumor suppressor genes
Tumor suppressor genes code for anti-proliferation signals and proteins that suppress mitosis and cell growth. Generally tumor suppressors are transcription factors that are activated by cellular stress or DNA damage. In the field of Molecular biology, a transcription factor (sometimes called a sequence-specific DNA binding factor is a Protein that binds to specific sequences Often DNA damage will cause the presence of free-floating genetic material as well as other signs, and will trigger enzymes and pathways which lead to the activation of tumor suppressor genes. The functions of such genes is to arrest the progression of cell cycle in order to carry out DNA repair, preventing mutations from passing on to daughter cells. Canonical tumor suppressors include the p53 gene, which is a transcription factor activated by many cellular stress including hypoxia and ultraviolet radiation damage. p53 (also known as protein 53 or tumor protein 53) is a Transcription factor encoded by the TP53 gene Chronic Hypoxia is a pathological condition in which the body as a whole ( generalized hypoxia) or region of the body ( tissue hypoxia) is deprived of adequate Ultraviolet ( UV) light is Electromagnetic radiation with a Wavelength shorter than that of Visible light, but longer than X-rays
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.
Multiple mutations
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 and tumor suppressor genes, which was first hypothesised by the Knudson hypothesis. A hypothesis (from Greek) consists either of a suggested explanation for a phenomenon (an event that is observable or of a reasoned proposal suggesting a possible The Knudson hypothesis is the Hypothesis that Cancer is the result of accumulated Mutations to a cell's DNA. 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. In Information technology, backup refers to making copies of Data so that these additional copies may be used to restore the original after a 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. Often, because these genes regulate the processes that prevent most damage to genes themselves, the rate of mutations increase as one gets older, because DNA damage forms a feedback loop. Feedback is a circular causal Process whereby some proportion of a system's output is returned (fed back to the Input.
Usually, oncogenes are dominant alleles, as they contain gain-of-function mutations, while mutated tumor suppressors are recessive alleles, as they contain loss-of-function mutations. In biology mutations are changes to the Nucleotide sequence of the Genetic material of an organism In biology mutations are changes to the Nucleotide sequence of the Genetic material of an organism Each cell has two copies of a same gene, one from each parent, and under most cases gain of function mutation in one copy of a particular proto-oncogene is enough to make that gene a true oncogene, while usually loss of function mutation need to happen in both copies of a tumor suppressor gene to render that gene completely non-functional. However, cases exist in which one loss of function copy of a tumor suppressor gene can render the other copy non-functional, and this is called the dominant negative effect. This is observed in many p53 mutations.
Mutation of tumor suppressor genes that are passed on to the next generation of not merely cells, but their offspring can cause increased likelihoods for cancers to be inherited. In Biology, offspring are the product of Reproduction, a new Organism produced by one or more Parents Collective offspring may be known Members within these families have increased incidence and decreased latency of multiple tumors. The mode of inheritance of mutant tumor suppressors is that affected member inherits a defective copy from one parent, and a normal copy from another. Because mutations in tumor suppressors act in a recessive manner (note, however, there are exceptions), the loss of the normal copy creates the cancer phenotype. A phenotype is any observable characteristic of an Organism, such as its morphology, Development, biochemical or physiological properties For instance, individuals who are heterozygous for p53 mutations are often victims of Li-Fraumeni syndrome, and those who are heterozygous for Rb mutations develop retinoblastoma. Zygosity refers to the genetic condition of a Zygote. In genetics zygosity describes the similarity or dissimilarity of DNA between Homologous Li-Fraumeni syndrome is a rare Autosomal dominant Hereditary disorder. The retinoblastoma protein (abbreviated pRb or Rb) is a Tumor suppressor Protein that is dysfunctional in many types of Cancer Retinoblastoma is a Cancer of the Retina. Development of this tumor is initiated by Mutations ref> that inactivate both copies of the RB1 Similarly, mutations in the adenomatous polyposis coli gene are linked to adenopolyposis colon cancer, with thousands of polyps in colon while young, while mutations in BRCA1 and BRCA2 lead to early onset of breast cancer. Familial adenomatous polyposis ( FAP) is an inherited condition in which numerous polyps form mainly in the Epithelium of the large intestine. Familial adenomatous polyposis ( FAP) is an inherited condition in which numerous polyps form mainly in the Epithelium of the large intestine. BRCA1 ( Breast cancer 1 early onset is a Human Gene, some mutations of which are associated with a significant increase in the risk of Breast cancer BRCA2 (Breast Cancer Type 2 susceptibility protein is a Human Gene that is involved in the repair of chromosomal Breast cancer is a Cancer that starts in the cells of the Breast in women and men
Non-mutagenic carcinogens
Many mutagens are also carcinogens, but some carcinogens are not mutagens. In Biology, a mutagen ( Latin, literally origin of change) is a physical or chemical agent that changes the genetic information (usually DNA) The term carcinogen refers to any substance Radionuclide or radiation that is an agent directly involved in the promotion of Cancer or in the fatation of its propagation Examples of carcinogens that are not mutagens include alcohol and estrogen. In Chemistry, an alcohol is any Organic compound in which a Hydroxyl group ( - O[[hydrogen H]]) is bound to a Carbon Estrogens (US otherwise oestrogens or œstrogens) are a group of Steroid compounds named for their importance in the Estrous cycle, These are thought to promote cancers through their stimulating effect on the rate of cell mitosis. Mitosis is the process in which a Eukaryotic cell separates the Chromosomes in its Cell nucleus, into two identical sets in two daughter nuclei Faster rates of mitosis increasingly leave less opportunities for repair enzymes to repair damaged DNA during DNA replication, increasingly the likelihood of a genetic mistake. DNA replication is the process of copying a double-stranded DNA molecule to form two double-stranded molecules 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. A chromosome is an organized structure of DNA and Protein that is found in cells. Aneuploidy is defined as an abnormal number of Chromosomes Syndromes caused by an extra or missing chromosome are among the most widely recognized Genetic disorders
Role of viral infections
Furthermore, many cancers originate from a viral infection; this is especially true in animals such as birds, but less so in humans. A virus (from the Latin virus meaning Toxin or Poison) is a sub-microscopic infectious agent that is unable An infection is the detrimental Colonization of a host Organism by a foreign Species. Birds ( class Aves) are bipedal endothermic ( Warm-blooded) Vertebrate animals that lay eggs. Human beings, humans or man (Origin 1590–1600 L homō man OL hemō the earthly one (see Humus Viruses are responsible for 15% of human cancers. The mode of virally-induced tumors can be divided into two, acutely-transforming or slowly-transforming. In acutely transforming viruses, the viral particles carry a gene that encodes for 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, especially as viral genome insertion is obligatory part of retroviruses, near a proto-oncogene in the host genome. A retrovirus is any Virus belonging to the viral family Retroviridae. The viral promoter or other transcription regulation elements in turn cause over-expression of that proto-oncogene, which in turn induces uncontrolled cellular proliferation. In Biology, a promoter is a region of DNA that facilitates the transcription of a particular Gene. Because viral genome insertion is not specific to proto-oncogenes and the chance of insertion near that proto-oncogene is low, slowly-transforming viruses have very long tumor latency compared to acutely-transforming virus, which already carries the viral-oncogene.
How viruses are thought to cause cancer
Viruses that are known to cause cancer such as HPV and cervical cancer, Hepatitis B and liver cancer and EBV and a type of lymphoma are all DNA viruses. It is thought that when the virus infects a cell it inserts a part of its own DNA near the cell growth genes causing cell division. The group of changed cells that are formed from the first cell dividing all have the same viral DNA near the cell growth genes. The group of changed cells are now special because one of the normal controls on growth has been lost.
Cells depending on their location can be damaged through radiation e. g. sunshine, chemicals e. g. cigarette smoke, inflammation e. g. bacterial infection or other viruses. Each cell has a chance of damage, a step on a path towards cancer. Cells often die if they are damaged, through failure of a vital process or the immune system however sometimes damage will knock out a single cancer gene. In an old person there are thousands, tens of thousands or hundreds of thousands of knocked out cells. The chance that any one would form a cancer is very low.
When the damage occurs in any area of changed cells something different occurs. Each of the cells has the potential for growth. The changed cells will divide quicker when the area is damaged by physical, chemical or viral agents. A vicious cycle has been set up. Damaging the area will cause the changed cells to divide and then it is more likely they will suffer knock outs.
This model of carcinogenesis is popular because it explains why cancers grow. It would be expected that cells that are damaged through radiation would die or at least be worse off because they have fewer genes working, viruses increase the number of genes working.
One concern is that we may end up with thousands of vaccines to prevent every virus that can change our cells. Viruses can have different effects on different parts of the body. It may be possible to prevent a number of different cancers by immunising against one viral agent. It is likely that HPV for instance has a role in cancers of the mucous membranes of the mouth.
Etiology
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. Molecular biology is the study of Biology at a molecular level Prognosis (older Greek πρόγνωσις modern Greek πρόγνωση - literally fore-knowing foreseeing) is a medical term denoting the For example, up to half of all tumors have a defective p53 gene. This mutation is associated with poor prognosis, since those tumor cells are less likely to go into apoptosis or programmed cell death when damaged by therapy. Programmed cell-death ( PCD) is death of a cell in any form mediated by an intracellular program Telomerase mutations remove additional barriers, extending the number of times a cell can divide. Telomerase is an Enzyme that adds specific DNA sequence repeats ("TTAGGG" in all vertebrates to the 3' ("three prime" end of DNA strands in the Other mutations enable the tumor to grow new blood vessels to provide more nutrients, or to metastasize, spreading to other parts of the body. Angiogenesis is a physiological process involving the growth of new Blood vessels from pre-existing vessels Metastasis ( Greek: displacement μετά=next + στάσις=placement, plural metastases) sometimes abbreviated mets,
Cancer stem cells
A new way of looking at carcinogenesis comes from integrating the ideas of developmental biology into oncology. Cancer stem cells (CSCs are a sub-population of Cancer cells (found within Tumors or Hematological cancers that possess characteristics normally associated Developmental Biology is the official journal of the Society for Developmental Biology. Oncology is the branch of medicine that studies Tumors ( Cancer) and seeks to understand their development diagnosis treatment and prevention The cancer stem cell paradigm proposes that some or all cancers arise from transformation of adult stem cells. Cancer stem cells (CSCs are a sub-population of Cancer cells (found within Tumors or Hematological cancers that possess characteristics normally associated The word paradigm ( Greek:παράδειγμα (paradigmacomposite from para- and the verb δείχνυμι "to show" as a whole -roughly- meaning "example" Adult stem cells are undifferentiated cells found throughout the body after embryonic development that divide to replenish dying cells and regenerate damaged These cells persist as a subcomponent of the tumor and retain key stem cell properties. Furthermore, the relapse of cancer and the emergence of metastasis are also attributed to these cells. A relapse (etymologically "who falls again" occurs when a person is affected again by a condition that affected them in the past Metastasis ( Greek: displacement μετά=next + στάσις=placement, plural metastases) sometimes abbreviated mets, The cancer stem cell hypothesis does not contradict earlier concepts of carcinogenesis. Cancer stem cells (CSCs are a sub-population of Cancer cells (found within Tumors or Hematological cancers that possess characteristics normally associated A hypothesis (from Greek) consists either of a suggested explanation for a phenomenon (an event that is observable or of a reasoned proposal suggesting a possible It simply points to adult stem cells as the site where the process begins. Adult stem cells are undifferentiated cells found throughout the body after embryonic development that divide to replenish dying cells and regenerate damaged
Non-mainstream theories
There are a number of theories of carcinogenesis and cancer treatment which fall outside the mainstream of scientific opinion, due to lack of scientific rationale, logic, or evidence base. These theories may be used to justify various alternative cancer treatments. They should be distinguished from those theories of carcinogenesis which have a logical basis within mainstream cancer biology, and from which conventionally testable hypotheses can be made.
References
- Knudson AG (2001). "Two genetic hits (more or less) to cancer". Nat Rev Cancer 1 (2): 157–62. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 11905807.
- Fearon ER, Vogelstein B (1990). "A genetic model for colorectal tumorigenesis". Cell 61 (5): 759–67. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 2188735.
- Dixon K, Kopras E (2004). "Genetic alterations and DNA repair in human carcinogenesis. ". Semin Cancer Biol 14 (6): 441–8. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 15489137.
- Sarasin A (2003). "An overview of the mechanisms of mutagenesis and carcinogenesis. ". Mutat Res 544 (2-3): 99–106. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 14644312.
- Schottenfeld D, Beebe-Dimmer JL (2005). "Advances in cancer epidemiology: understanding causal mechanisms and the evidence for implementing interventions. ". Annu Rev Public Health 26: 37–60. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 15760280.
- Wicha MS, Liu S, Dontu G (2006). "Cancer stem cells: an old idea--a paradigm shift. ". Cancer Res 66: 1883–90. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 16488983.
- The Basic Science of Oncology. Tannock IF, Hill RP et al (eds) 4th ed. 2005 McGraw-Hill.
- Principles of Cancer Biology. Kleinsmith, LJ (2006). Pearson Benjamin Cummings.
See also
Cancer (medical term Malignant Neoplasm) is a class of Diseases in which a group of cells display uncontrolled Cancer research is research into Cancer in order to identify causes and develop strategies for prevention diagnosis treatments and cure The term carcinogen refers to any substance Radionuclide or radiation that is an agent directly involved in the promotion of Cancer or in the fatation of its propagation In Biology, a mutagen ( Latin, literally origin of change) is a physical or chemical agent that changes the genetic information (usually DNA) An oncogene is a protein encoding Gene, which — when deregulated — participates in the onset and development of Cancer. A tumor suppressor gene, or antioncogene is a Gene that protects a cell from one step on the path to cancerDapyx Software network: MP3 Explorer | Ebook Manager | Zenithic