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Most cancers are thought to arise because of changes that occur during the lifetime of the affected person. Some cancer have been linked to defective (mutant) genes that are inherited from the person's parent(s). The cancer itself is not inherited, but the defective genes make it more likely that particular cancers will occur. Families with these genes can have much more cancer than others.
The National Cancer Institute’s list of common cancer-related inherited genetic mutations includes mutations that affect several different tumor suppressorA gene that functions in the control of cell division. Tumor suppressors normally work to limit cell division and may be contrasted with oncogenes. genes. The cancers caused by inherited changes to tumor suppressor genes include breast cancer, ovarian cancer, prostate cancer, leukemiaA cancer affecting the cells that develop into white or red blood cells. Both of these cell types originate from stem cells in bone marrow. Red blood cells function to carry oxygen to our tissues and the white cells (leukocytes) are part of our immune system. The cancerous cells often accumulate in the blood., pancreatic cancer, and colon cancer.
NOTE: Only a portion of each of these cancer types is linked to inherited mutations. The rest of the cases are called ‘sporadic’, and they are not hereditary.
Many cancers are now routinely tested to see if they are candidates for treatment with targeted drugs. This includes some of those linked to hereditary cancer syndromes and a growing list of other cancers.
Because the cancers on the list below can be due to inherited geneA stretch of DNA that leads to the production of an RNA. The RNA is produced during the process of transcription. This RNA can be used to guide the formation of a protein via translation or can be used directly in the cell. mutations, many people diagnosed with them chose to get tested to see if they have the gene of interest.
Learn about genetic testing at the Winship Cancer Institute of Emory University.
Learn more about targeted cancer treatments.
Below are short descriptions of some of the better understood hereditary cancers:
Hereditary Breast Cancer
Li-Fraumeni syndrome
Cowden syndrome
Lynch syndrome
Familial Adenomatous PolyposisAlso: FAP. An inherited form of colon cancer characterized by the development of hundreds to thousands of colonic polyps. Most of these polyps are harmless but some eventually progress to malignant growths. FAP is often diagnosed via colonoscopy.
RetinoblastomaA cancer of the retina. Found most often in small children; this disease has been linked to the inheritance of mutated copies of the Rb tumor suppressor gene. For more information, see the entries on Rb and Tumor Suppressor.
Multiple Endocrine Neoplasia
Von-Hippel Lindau Syndrome
Genes: BRCA1, BRCA2
Related cancer types: Female breast and ovarian cancers, and other cancers, including prostate, pancreatic, and male breast cancer
BRCA1 and BRCA2 are tumor suppressor genes; their proteinOne of the four basic types of biomolecule. Proteins are polymers made up of strings of amino acids. Proteins serve many functions in organisms including transport of molecules, structure, cell adhesion and as signaling molecules such as hormones. Many transcription factors, including p53 and Rb are proteins. products are responsible for preventing uncontrolled cell division. Specifically, the BRCA1 and BRCA2 proteins are involved in repairing DNAAbbreviation for deoxyribonucleic acid. Composed of very long strings of nucleotides, which are abbreviated as A, C, G and T. DNA is the storage form of our genetic material. All of the instructions for the production of proteins are encoded in our DNA. damage and controlling other genes. The reason why mutations in these genes are specifically linked to breast and ovarian cancer is not completely clear, but it may be linked to the hormoneA chemical produced by cells that alters the activity of other cells. The chemicals may be lipids, such as testosterone and estrogen or proteins like insulin. Hormones may act at locations far from their site of origin. Estrogen, for example, is produced primarily by cells in the ovaries but acts on cells in the breast and elsewhere. estrogenA steroid sex hormone. Estrogen's structure is closely related to cholesterol. Produced by the ovaries, estrogen has effects on the reproductive, cardiovascular and skeletal systems. Estrogen is also a growth factor for some types of cells, including breast cells. Inhibitors of estrogen function such as tamoxifen and arimidex are used to block the growth effects of estrogen. See also, estrogen receptor.. Breast and ovarian cells depend on the hormone estrogen to reproduce –and they respond to changing levels of estrogen (levels of estrogen are affected by the menstrual cycle and puberty, for example). The rapid division caused by estrogen may lead to increased mutation in these genes and the subsequent development of cancer.
Gene: TP53
Related cancer types: Breast cancer, soft tissue sarcomaA malignant cancer that originates in bone, muscle or connective tissues., osteosarcomaCancer of the bone. Osteosarcomas are derived from osteoblasts, cells that line the outside of bones. It is most common among children and young adults and affects males more than females. (bone cancer), leukemia, brain tumors, adrenocortical carcinomaCancer of epithelial cells, the cells that cover the outside and inside of body surfaces. This is the most common form of cancer. (cancer of the adrenal glands), and other cancers.
The TP53 gene (also known as p53A tumor suppressor gene that is mutated in over 50% of cancers of all types. The p53 protein is a transcription factor that controls entry into the cell division cycle. Many signals about the health of a cell are relayed to the p53 protein. This results in a decision by the cell as to whether or not cell division should occur. If the cell is damaged and can not be repaired, the p53 protein is involved in triggering a chain of events that causes the cell to kill itself in a process termed apoptosis. Cells defective for p53 do not have these controls and tend to divide even when conditions are not favorable. Like all tumor suppressors, the p53 gene is normally involved in slowing or monitoring cell division.) codes for a very important tumor suppressor protein. It is involved in many activities that prevent cells from dividing uncontrollably. The important activities regulated by p53 include DNA repair, cell death (apoptosisAlso called programmed cell death. Apoptosis is a natural process that occurs throughout the lives of almost all animals and plants. The death of the cells is a carefully controlled process that does not generate any inflammation.), and control of the cell cycle. It is referred to as a “gatekeeper” gene, since its job is to ultimately protect the body from tumor formation. Inherited mutations in TP53 cause a person to be very susceptible to many kinds of cancers, since it is one of the body’s main defenses against cancer-causing activities.
Gene: PTEN (phosphatase and tensin homolog)
Related cancer types: Breast, thyroid, endometrialRefers to the endometrium, the inner lining of the uterus. The endometrium is a common site of cancer. (uterine lining), and other cancers
PTEN is also a tumor suppressor gene. Like TP53, if PTEN is defective, cells may continue dividing, even though cancer-causing changes may be present. Specifically, the product of PTEN controls whether or not cells respond to messages telling them to either divide or undergo apoptosis (the cell version of suicide). If regulation of these messages is disabled, cells may end up dividing out of control, and a tumor may form. PTEN mutations are responsible for Cowden syndrome, which includes the formation of many hamartomas, which are non-malignantA tumor that has invaded neighboring tissue. growths. Mutations also lead to an increased risk for breast cancer, thyroid cancer, and endometrial cancer (cancer of the uterine lining).
Genes: MSH2, MLH1, MSH6, PMS2, EPCAM
Related cancer types: Colorectal, endometrial, ovarian, renal pelvis, pancreatic, small intestine, liver and biliary tract, stomach, brain, and breast cancers
The genes involved in Lynch syndrome are DNA mismatch repair genes. The proteins encoded by these genes are responsible for correcting mistakes made when DNA is copied (DNA replicationThe process by which DNA is duplicated. DNA replication occurs during the S phase (synthesis) of the cell cycle. Many chemotherapy drugs act during DNA replication. Some are incorporated into the newly replicated DNA and cause problems. Others interfere with enzymes necessary for DNA replication. See topoisomerase.). When these genes are defective, the proteins cannot repair DNA properly. Often, the cancers associated with Lynch syndrome can be identified by ‘microsatellite instability'. Microsatellite is a term for a repeating sequence of DNA, such as CGCGCGCGG or TATATATAT. The human genomeThe full set of genes in an organism. Humans have an estimated 25,000 protein-encoding genes in their genome. has many of these repeating sequences. Microsatellite instability means that the mutations specifically occur in these repeating sequences of DNA. Usually, there is a loss or gain of some repeats (i.e. CAGCAGCAG turns into CAGCAG). The changes in the repeated sequences can affect the stability of the DNA and can lead to cancer of many kinds.
Gene: APC (adenomatous polyposis coli)
Related cancer types: Colorectal cancer, tumors in the small intestine, brain, stomach, bone, skin, and other tissues. Also associated with non-cancerous (benignA growth that does not leave its site of origin or invade surrounding tissue. Benign growths can get large and are capable of causing illness or even death, depending on the location of the growth. Technically, benign growths are not cancer.) growths (polps) of the colon and small intestine.
APC is a tumor suppressor gene that controls how often a cell divides, how cells stick to each other, and cell movement. APC is also involved in DNA damage detection and works with other proteins involved in cell-cell communication. Many different mutations in APC are known to cause familial adenomatous polyposis, a condition associated with the development of many, frequently hundreds, of polyps. It is very likely that at least one of the polyps will become cancerous at some time in the patient’s life. A defective APC protein can also cause desmoid tumors, which are thick benign tumors that arise from connective tissue.
Gene: RB1 (retinoblastoma)
Related cancer types: Eye cancer (cancer of the retina), pinealoma (cancer of the pineal gland), osteosarcoma, melanoma, and soft tissue sarcoma
The RB1 gene codes for the RbA tumor suppressor. The Rb gene is mutated in many different cancers but was initially described due to its role in the development of an eye cancer, retinoblastoma, which usually strikes young children. The protein product of the gene is a transcription factor that controls the expression of genes important in driving cells into the division process. protein, which is a tumor suppressor. Rb is responsible for halting cell division if conditions are not optimal (i.e. there is DNA damage that must be repaired, or the cell is stressed in some way). It has roles in controlling other proteins involved in DNA replication, apoptosis, and cell maturation (differentiationThe maturation of a stem cell into a fully functional cell. Fully differentiated cells are often not able to divide and many cancers are thought to arise via mutations in the small number of stem cells that remain in the tissue.). When there is a mutation in the RB1 gene, the Rb protein may not work, so cell growth goes unregulated. For reasons that are not completely clear, changes to RB1 tend to cause cancer in the eye, specifically in the retina. When one mutated copy of the retinoblastoma gene is inherited (causing cancers known as germinal or familial retinoblastoma), the mutant gene is present in every cell in the body, leaving the person highly susceptible to other types of cancer, primarily the pineal gland, bones, soft tissue and skin.
Gene: MEN1
Related cancer types: Pancreatic endocrine tumors and (usually benign) parathyroid and pituitary gland tumors
MEN1 codes for a tumor suppressor protein called menin. The exact function of menin is unknown, but it appears to be involved in regulating cell division, DNA repair, and apoptosis. Over a thousand different mutations in the MEN1 gene are known to cause multiple endocrine neoplasia type 1. MEN type 1 involves tumor growth in endocrine glands (the glands in the body that produce hormones). The endocrine glands commonly affected by multiple endocrine neoplasia type 1 are the parathyroid gland, the pituitary gland, and the pancreas. Usually, a mutation in MEN1 leads to a shortened version of the menin protein, which is unstable and easily broken down. When this happens, one copy of the MEN1 gene does not produce a functioning menin protein. If a mutation arsies in the second copy (which is common in endocrine glands, although the reason for this is unknown) the cell cannot produce any functional menin at all, which can lead to uncontrolled cell division and cancer.
Gene: RET
Related cancer types: Medullary thyroid cancer and pheochromocytoma (benign adrenal gland tumor)
The RET gene is a proto-oncogeneA gene that normally functions to promote cell division. When these genes are mutated they may produce products that promote cell division in an abnormal fashion. Examples of oncogenes include HER2/neu, ras, and src. See Tumor Suppressors and Oncogenes for more details. that is involved in cell signaling. It spans the cell membraneA thin barrier between the cytoplasm and the extracellular space. Cell membranes are composed mainly of lipids and proteins. A hallmark of cellular membranes is their selective permeability to certain ions and other molecules., and acts as a receptor for signals that help cells respond to changes in their environment. MEN2 can be divided into three subtypes: MEN2A, MEN2B, and Familial Medullary Thyroid Carcinoma (FMTC). Most mutations in the RET gene that cause MEN2 are very small (point) mutations that change only one amino acidA monomer building block used to build proteins. There are many amino acids but only about twenty different kinds are found in most proteins. in the protein. Many of these mutations are associated with inherited (familial) medullary thyroid cancer.
Gene: VHL
Related cancer types: Kidney cancer and multiple noncancerous tumors, including pheochromocytoma
The VHL gene works with other proteins to form the VCB-CUL2 complex. This complex causes other proteins in the cell to be broken down when they are damaged or no longer needed. One target of the VCB-CUL2 complex is hypoxia-inducible factor-2-alpha (HIF-2a). HIF-2a coordinates the body’s response to changes in oxygen levels by controlling cell division, and the formation of new blood vessels and red blood cells. When oxygen levels are normal, the VCB-CUL2 complex puts the brakes on HIF-2a. When VHL is mutated, the VCB-CUL2 complex cannot function properly, and can’t degrade HIF-2a or other proteins when they are damaged or not needed. HIF-2a may then stimulate excessive cell division and blood vessel formation, which leads to tumor and cyst formations, both characteristic of Von Hippel-Lindau syndrome.
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