The truth and how to prevent cancer

• What is cancer?
• What causes cancer
• Can it be prevented?
• How is it diagnosed

What causes cancer Origins of cancer mutations. Other types of mutations can Cell division or cell proliferation is a be caused by chronic inflammation, as physiological process that occurs in neutrophil granulocytes secrete free almost all tissues and under many radicals that damage DNA. Chromosomal circumstances. Normally the balance translocations, such as the Philadelphia between proliferation and programmed chromosome, are a special type of cell death is tightly regulated to mutation that involve exchanges between ensure the integrity of organs and different chromosomes. tissues. Mutations in DNA that lead to Many mutagens are also carcinogens, but cancer disrupt these orderly processes. some carcinogens are not mutagens. The uncontrolled and often rapid Examples of carcinogens that are not proliferation of cells can lead to mutagens include alcohol and estrogen. either a benign tumor or a malignant These are thought to promote cancers tumor (cancer). Benign tumors do not through their stimulating effect on the spread to other parts of the body or rate of cell mitosis. Faster rates of invade other tissues, and they are mitosis increasingly leave less rarely a threat to life unless they opportunities for repair enzymes to extrinsically compress vital structures. repair damaged DNA during DNA Malignant tumors can invade other replication, increasing the likelihood organs, spread to distant locations of a genetic mistake. A mistake made (metastasize) and become during mitosis can lead to the daughter life-threatening. cells receiving the wrong number of Molecular biology chromosomes, which leads to aneuploidy Carcinogenesis, which means the and may lead to cancer. initiation or generation of cancer, is Furthermore, many cancers originate from the process of derangement of the rate a viral infection; this is especially of cell division due to damage to DNA. true in animals such as birds, but also Cancer is, ultimately, a disease of in humans, as viruses are responsible genes. In order for cells to start for 15% of human cancers worldwide. The dividing uncontrollably, genes which main viruses associated with human regulate cell growth must be damaged. cancers are human papillomavirus, Proto-oncogenes are genes which promote hepatitis B virus, Epstein-Barr virus, cell growth and mitosis, a process of and human T-lymphotropic virus. cell division, and tumor suppressor Experimental and epidemiologic data genes discourage cell growth, or imply a causative role for viruses and temporarily halt cell division in order they appear to be the second most to carry out DNA repair. Typically, a important risk factor for cancer series of several mutations to these development in humans, exceeded only by genes are required before a normal cell tobacco usage The mode of transforms into a cancer cell. virally-induced tumors can be divided Proto-oncogenes promote cell growth into two, acutely-transforming or through a variety of ways. Many can slowly-transforming. In acutely produce hormones, a "chemical messenger" transforming viruses, the viral between cells which encourage mitosis, particles carry a gene that encodes for the effect of which depends on the an overactive oncogene called signal transduction of the receiving viral-oncogene (v-onc), and the infected tissue or cells. Some are responsible cell is transformed as soon as v-onc is for the signal transduction system and expressed. In contrast, in signal receptors in cells and tissues slowly-transforming viruses, the virus themselves, thus controlling the genome is inserted, especially as viral sensitivity to such hormones. They often genome insertion is an obligatory part produce mitogens, or are involved in of retroviruses, near a proto-oncogene transcription of DNA in protein in the host genome. The viral promoter synthesis, which creates the proteins or other transcription regulation and enzymes responsible for producing elements in turn cause overexpression of the products and biochemicals cells use that proto-oncogene, which in turn and interact with. induces uncontrolled cellular Mutations in proto-oncogenes can modify proliferation. Because viral genome their expression and function, insertion is not specific to increasing the amount or activity of the proto-oncogenes and the chance of product protein. When this happens, they insertion near that proto-oncogene is become oncogenes, and thus cells have a low, slowly-transforming viruses have higher chance to divide excessively and very long tumor latency compared to uncontrollably. The chance of cancer acutely-transforming viruses, which cannot be reduced by removing already carry the viral-oncogene. proto-oncogenes from the genome as they It is impossible to tell the initial are critical for growth, repair and cause for any specific cancer. However, homeostasis of the body. It is only when with the help of molecular biological they become mutated that the signals for techniques, it is possible to growth become excessive. characterize the mutations or Tumor suppressor genes code for chromosomal aberrations within a tumor, anti-proliferation signals and proteins and rapid progress is being made in the that suppress mitosis and cell growth. field of predicting prognosis based on Generally tumor suppressors are the spectrum of mutations in some cases. transcription factors that are activated For example, some tumors have a by cellular stress or DNA damage. Often defective p53 gene. This mutation is DNA damage will cause the presence of associated with poor prognosis, since free-floating genetic material as well those tumor cells are less likely to go as other signs, and will trigger enzymes into apoptosis or programmed cell death and pathways which lead to the when damaged by therapy. Telomerase activation of tumor suppressor genes. mutations remove additional barriers, The functions of such genes is to arrest extending the number of times a cell can the progression of cell cycle in order divide. Other mutations enable the tumor to carry out DNA repair, preventing to grow new blood vessels to provide mutations from being passed on to more nutrients, or to metastasize, daughter cells. Canonical tumor spreading to other parts of the body. suppressors include the p53 protein, Malignant tumors cells have distinct which is a transcription factor properties: activated by many cellular stressors evading apoptosis including hypoxia and ultraviolet unlimited growth potential radiation damage. (immortalitization) due to overabundance Despite nearly half of all cancers may of telomerase involve alterations in p53, its tumor self-sufficiency of growth factors suppressor function is poorly insensitivity to anti-growth factors understood. It is clear it has two increased cell division rate functions: one a nuclear role as a altered ability to differentiate transcription factor, and the other a no ability for contact inhibition cytoplasmic role in cell cycle and ability to invade neighbouring tissues division regulation and apoptosis. ability to build metastases at distant The Warburg effect is the preferential sites use of glycolyisis for energy to sustain ability to promote blood vessel growth cancer growth. p53 has been shown to (angiogenesis) regulate the shift from the respiratory A cell that degenerates into a tumor to the glycolytic pathway. Synthesis of cell does not usually acquire all these Cytochrome c Oxidase 2 (SCO2) has been properties at once, but its descendant recognized as the downstream mediator of cells are selected to build them. This this effect. SCO2 is critical for process is called clonal evolution. A regulating the cytochrome c oxidase first step in the development of a tumor complex within the mitochondria, and p53 cell is usually a small change in the can disprutpt the SCO2 gene. P53 DNA, often a point mutation, which leads regulation of SCO2 and mitochondrial to a genetic instability of the cell. respiration may provide a possible The instability can increase to a point explanation for the Warburg effec where the cell loses whole chromosomes, However, a mutation can damage the tumor or has multiple copies of several. Also, suppressor gene itself, or the signal the DNA methylation pattern of the cell pathway which activates it, "switching changes, activating and deactivating it off". The invariable consequence of genes without the usual regulation. this is that DNA repair is hindered or Cells that divide at a high rate, such inhibited: DNA damage accumulates as epithelials, show a higher risk of without repair, inevitably leading to becoming tumor cells than those which cancer. divide less, for example neurons. In general, mutations in both types of Morphology genes are required for cancer to occur. Cancer tissue has a distinctive For example, a mutation limited to one appearance under the microscope. Among oncogene would be suppressed by normal the distinguishing traits are a large mitosis control and tumor suppressor number of dividing cells, variation in genes, which was first hypothesised as nuclear size and shape, variation in the Knudson hypothesis. A mutation to cell size and shape, loss of specialized only one tumor suppressor gene would not cell features, loss of normal tissue cause cancer either, due to the presence organization, and a poorly defined tumor of many "backup" genes that duplicate boundary. Immunohistochemistry and other its functions. It is only when enough molecular methods may characterise proto-oncogenes have mutated into specific markers on tumor cells, which oncogenes, and enough tumor suppressor may aid in diagnosis and prognosis. genes deactivated or damaged, that the Biopsy and microscopical examination can signals for cell growth overwhelm the also distinguish between malignancy and signals to regulate it, that cell growth hyperplasia, which refers to tissue quickly spirals out of control. Often, growth based on an excessive rate of because these genes regulate the cell division, leading to a larger than processes that prevent most damage to usual number of cells but with a normal genes themselves, the rate of mutations orderly arrangement of cells within the increase as one gets older, because DNA tissue. This process is considered damage forms a feedback loop. reversible. Hyperplasia can be a normal Knudson’s two hit model has recently tissue response to an irritating been challenged by several stimulus, for example callus. investigators. Inactivation of one Dysplasia is an abnormal type of allele of some tumor suppressor genes is excessive cell proliferation sufficient to cause tumors. This characterized by loss of normal tissue phenomena is called haploinsufficiency arrangement and cell structure. Often and has been demonstrated by a number of such cells revert to normal behavior, experimental approaches. Tumors caused but occasionally, they gradually become by haploinsufficiency usually have a malignant. later age of onset when compared with The most severe cases of dysplasia are those by a two hit process.[6] referred to as "carcinoma in situ." In Usually, oncogenes are dominant, as they Latin, the term "in situ" means "in contain gain-of-function mutations, place", so carcinoma in situ refers to while mutated tumor suppressors are an uncontrolled growth of cells that recessive, as they contain remains in the original location and loss-of-function mutations. Each cell shows no propensity to invade other has two copies of the same gene, one tissues. Nevertheless, carcinoma in situ from each parent, and under most cases may develop into an invasive malignancy gain of function mutation in one copy of and is usually removed surgically, if a particular proto-oncogene is enough to possible. make that gene a true oncogene, while Heredity usually loss of function mutation needs Most forms of cancer are "sporadic", and to happen in both copies of a tumor have no basis in heredity. There are, suppressor gene to render that gene however, a number of recognised completely non-functional. However, syndromes of cancer with a hereditary cases exist in which one loss of component, often a defective tumor function copy of a tumor suppressor gene suppressor allele. Examples are: can render the other copy certain inherited mutations in the genes non-functional. This phenomenon is BRCA1 and BRCA2 are associated with an called the dominant negative effect and elevated risk of breast cancer and is observed in many p53 mutations. ovarian cancer Mutation of tumor suppressor genes that tumors of various endocrine organs in are passed on to the next generation of multiple endocrine neoplasia (MEN types not merely cells, but their offspring 1, 2a, 2b) can cause increased likelihoods for Li-Fraumeni syndrome (various tumors cancers to be inherited. Members within such as osteosarcoma, breast cancer, these families have increased incidence soft-tissue sarcoma, brain tumors) due and decreased latency of multiple to mutations of p53 tumors. The mode of inheritance of Turcot syndrome (brain tumors and mutant tumor suppressors is that colonic polyposis) affected member inherits a defective Familial adenomatous polyposis an copy from one parent, and a normal copy inherited mutation of the APC gene that from another. Because mutations in tumor leads to early onset of colon carcinoma. suppressors act in a recessive manner Retinoblastoma in young children is an (although there are exceptions), the inherited cancer loss of the normal copy creates the Lifestyle factors cancer phenotype. For instance, The most consistent finding, over individuals who are heterozygous for p53 decades of research, is the strong mutations are often victims of association between tobacco use and Li-Fraumeni syndrome, and those who are cancers of many sites. Hundreds of heterozygous for Rb mutations develop epidemiological studies have confirmed retinoblastoma. Similarly, mutations in this association. Further support comes the APC gene are linked to from the fact that lung cancer death adenopolyposis colon cancer, with rates in the United States have mirrored thousands of polyps in colon while smoking patterns, with increases in young, while mutations in BRCA1 and smoking followed by dramatic increases BRCA2 lead to early onset of breast in lung cancer death rates and, more cancer. recently, decreases in smoking followed Cancer pathology is ultimately due to by decreases in lung cancer death rates the accumulation of DNA mutations that in men. Lifestyle choices cause cancer: negatively effect expression of tumour tobacco, diet, exercise, sex, alcohol, suppressor proteins or positivly effect and tanning choices are the major risks. the expression of proteins that drive "Most cancers are related to known the cell cycle. Substances that cause lifestyle factors." these mutations are known as mutagens, There is also a growing body of research and mutagens that cause cancers are that correlates cancer incidence with known as carcinogens. Particular the lower levels of melatonin produced substances have been linked to specific in the body when people spend more time types of cancer. Tobacco smoking is in bright-light conditions, as happens associated with lung cancer. Prolonged typically in the well-lit nighttime exposure to radiation, particularly environments of the more developed ultraviolet radiation from the sun, countries. This effect is compounded in leads to melanoma and other skin people who sleep fewer hours and in malignancies. Breathing asbestos fibers people who work at night, two groups is associated with mesothelioma. In more that are known to have higher cancer general terms, chemicals called mutagens rates. and free radicals are known to cause 1 A B C D E F 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128