A cancer syndrome or family cancer syndrome is a genetic disorder in which inherited genetic mutations in one or more genes affect an individual affected by the disease for cancer progression and may also cause the onset of the onset of this cancer. Cancer syndrome often not only shows a high risk of cancer, but also the development of independent primary tumor. Many of these syndromes are caused by mutations in tumor suppressor genes, genes involved in protecting cells from behind the cancer. Other genes that may be affected are DNA repair genes, oncogenes and genes involved in blood vessel production (angiogenesis). Common examples of hereditary cancer syndromes are hereditary ovary-breast cancer syndrome and hereditary non-polyposis colon cancer (Lynch's syndrome).
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Hereditary cancer syndrome underlies 5 to 10% of all cancers and there are more than 50 identifiable types of hereditary cancers. Scientific understanding of cancer susceptibility syndrome is actively developing: additional syndromes are found, the underlying biology becomes more pronounced, and the commercialization of the diagnostic genetic methodology improves clinical access. Given the prevalence of breast and colon cancers, the most commonly known syndromes include hereditary ovary-breast cancer syndrome (HBOC) and hereditary non-polyposis colon cancer (HNPCC, Lynch's syndrome).
Some rare cancers are strongly associated with hereditary predisposing cancer syndrome. Genetic testing should be considered with adrenocortical carcinoma; carcinoid tumors; diffuse gastric cancer; fallopian tubes/primary peritoneal cancers; leiomyosarcoma; medullary thyroid cancer; paraganglioma/pheochromocytoma; renal cell carcinoma from chromophobe, oncocytic hybrid, or oncocytoma histology; sebaceous carcinoma; and cord tumor with annular tubular. Primary care physicians can identify people at risk for heridatari cancer syndrome.
Maps Cancer syndrome
Genetics
Two copies of each gene exist in all the cells of the body and each is called an allele. Most cancer syndromes are transmitted in an autosomal dominant way of buying. In this case, only one wrong allele has to exist for an individual to have a tendency to cancer. Individuals with one normal allele and one wrong allele are known as heterozygotes. Heterozygous individuals and someone with two normal alleles (homozygous) will have a 50% chance of producing an affected child. Mutations in a hereditary gene are known as germline mutations and a further mutation in a normal allele results in the development of cancer. This is known as the two hit Knudson hypothesis, where the first hit of the gene is an inherited mutation and the second hit occurs later on. Since only one allele needs to be mutated (compared with both so-called "sporadic cancers"), individuals are more likely to develop cancer than the general population.
Less often, the syndrome can be transmitted as an autosomal recessive trait. Both gene alleles must mutate in autosomal recessive disorders for individuals to have a tendency to cancer. A person with two recessive alleles is known as a homozygous recessive. Both parents must have at least one wrong allele for a child to become homozygous recessive. If both parents have one mutant allele and one normal allele (heterozygote) then they have a 25% chance of generating a homozygous (predisposing) recessive child, 50% chance of producing a heterozygous child (a faulty gene carrier) and a 25% chance of producing a child with two normal allele.
Examples of dominant autosomal cancer syndromes are autoimmune lymphoproliferative syndrome (Canale-Smith syndrome), Beckwith-Wiedemann syndrome (although 85% of cases are sporadic), Birt-Hogg-Dubà © syndrome, Carney syndrome, familial chordoma, Cowden syndrome, dysplastic nevus syndrome with melanoma familial, familial adenomatous polyposis, hereditary ovary-hereditary breast syndrome, hereditary diffuse stomach cancer (HDGC), hereditary hereditary non-polyposis colon (Lynch syndrome), Howel-Evans syndrome of eosophageal cancer with tilosis, juvenile polyposis syndrome, Li -Fraumeni syndrome, endocrinopathic neoplasia type 1/2, double osteochondromatosis, neurofibromatosis type 1/2, nevoid basal cell carcinoma syndrome (Gorlin syndrome), Peutz-Jeghers syndrome, familial prostate cancer, renal cell cancer of hereditary leiomyomatosis (LRCC), papillary renal cell cancer (HPRCC), paraganglioma syndrome-hereditary pheochromocytoma, retinoblastoma, tuberous sclerosis, von Hippel-Lin dau disease and Wilm tumor.
Examples of autosomal recessive cancer syndromes are ataxia telangiectasia, Bloom syndrome, Fanconi anemia, PEOPLE-related polyposis, Rothmund-Thomson syndrome, Werner syndrome and Xeroderma pigmentosum.
Some examples
Although cancer syndrome shows an increased risk of cancer, the risks vary. For some of these diseases, cancer is not their main feature. The discussion here focuses on their relationship with an increased risk of cancer. This list is far from complete.
Fanconi anemia
Fanconi anemia (FA) is a disorder with a broad clinical spectrum, including: early onset and an increased risk of cancer; bone marrow failure; and congenital abnormalities. The most prominent manifestations of this disorder are those associated with hematopoeisis (blood production by bone marrow); these include aplastic anemia, myelodysplastic syndrome and acute myeloid leukemia. Hepatic tumors and squamous cell carcinoma of the esophagus, oropharynx and uvula are solid tumors commonly associated with FA. Congenital abnormalities include: skeletal anomalies (especially those affecting the hands), cafe au lait spots and hypopigmentation. To date, the genes known to cause FA are: FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ, FANCL, FANCM, FANCN, FANCO, FANCP and BRCA2 (formerly known as FANCD1). Inherited syndrome is particularly autosomal recessive, but FANCB may be inherited from x-linked resessive inheritance (maternal or xernal). The FA lines are involved in DNA repair when two DNA strands misjudged (interstrand crosslinks). Many paths coordinated by FA lines for this include repair of nucleotide excision, transect synthesis and homologous recombination.
Familial adenomatous polyposis
Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome that greatly increases the risk of colorectal cancer. About 1 in 8000 people will have this disease and have about 100% penetration. An individual with this disease will have hundreds to thousands of benign adenomas throughout their colon, which in many cases will develop into cancer. Other tumors increased in frequency including; osteomas, adrenal adenomas and carcinomas, thyroid tumors and desmoid tumors. The cause of this disorder is the mutated APC gene, which is involved in the cataton regulation. APC damage causes? -katu accumulates in cells and activates transcription factors involved in cell proliferation, migration, differentiation and apoptosis (programmed cell death).
Hereditary breasts and ovarian cancer
Hereditary breast-ovarian cancer syndrome (HBOC) is a dominant autosomal genetic disorder caused by genetic mutations of the BRCA1 and BRCA2 genes. In women, this disorder primarily increases the risk of breast and ovarian cancer, but also increases the risk of fallopian tube carcinoma and papillary serous carcinoma in the peritoneum. In men the risk of prostate cancer increases. Other cancers that are inconsistently associated with this syndrome are pancreatic cancer, male breast cancer, colorectal cancer and uterine and cervical cancer. Genetic mutations account for about 7% and 14% of breast and ovarian cancers, respectively, and BRCA1 and BRCA2 accounts for 80% of these cases. BRCA1 and BRCA2 are tumor suppressor genes involved in maintaining and repairing DNA, which in turn causes genomic instability. Mutations in this gene allow further damage to the DNA, which can cause cancer.
Hereditary non-polyposis colon cancer
Hereditary non-polyposis colon cancer (HNPCC), also known as Lynch syndrome, is an autosomal dominant cancer syndrome that increases the risk of colorectal cancer. This is due to genetic mutations in DNA mismatch repair genes (MMR), especially MLH1, MSH2, MSH6 and PMS2. In addition to colorectal cancer, many other cancers increase in frequency. These include; endometrial cancer, stomach cancer, ovarian cancer, colon cancer and pancreatic cancer. HNPCC is also associated with early onset of colorectal cancer. The MMR gene is involved in DNA repair when the base on each strand of DNA is not suitable. Damaged MMR genes allow the insertion and deletion of continuous mutations in the area of ​​DNA known as microsatellite. These recurrent sequences of this short DNA become unstable, leading to a state of microsatellite instability (MSI). Microsatellite mutations are often found in genes involved in tumor initiation and progression, and MSI can increase cell survival, leading to cancer.
Paraganglioma-pheochromocytoma hereditary syndrome
Most cases of familial paraganglioma are caused by mutations in the succinic acid dehydrogenase (SDH, succinic: ubiquinone oxidoreductase) (SDHD, SDHAF2, SDHC, SDHB) subunit genes.
PGL-1 is associated with SDHD mutations, and most individuals with PGL-1 with paraganglioma have affected the father rather than the affected mother. PGL1 and PGL2 autosomes are dominant with printing. PGL-4 is associated with SDHB mutations, and is associated with a higher risk of pheochromocytoma, as well as kidney cell cancer and non-medullary thyroid cancer.
Li-Fraumeni Syndrome
Li-Fraumeni syndrome is an autosomal dominant syndrome primarily caused by mutations in the TP53 gene, which greatly increases the risk of many cancers and is also strongly associated with early onset of this cancer. Cancers associated with this disorder include; soft tissue sarcomas (commonly found in childhood), osteosarcoma, breast cancer, brain cancer, leukemia and adrenocortical carcinoma. Individuals with Li-Fraumeni syndrome often have some independent primary cancers. The reason for the large clinical spectrum of this disorder may be due to mutations of other genes that modify the disease. Proteins produced by the TP53 gene, p53, are involved in cell cycle capture, DNA repair and apoptosis. The damaged P53 may not be able to perform this process properly, which may be the reason for tumor formation. Since only 60-80% of individuals with abnormalities have mutations detected in TP53, other mutations in the p53 pathway may be involved in Li-Fraumeni syndrome.
MUTYH-associated polyposis shares most of its clinical features with FAP; the difference is that it is an autosomal recessive disorder caused by a mutation in the DNA repair gene MUTYH. Tumors with an increased risk of this disorder are colorectal cancer, gastric adenoma and duodenal adenoma.
Nevoid basal cell carcinoma syndrome
Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome, is the dominant autosomal cancer syndrome in which the risk of basal cell carcinoma is very high. The disease is characterized by basal cell nevi, jaw keratocyst and skeletal abnormalities. Estimates of NBCCS prevalence vary, but roughly 1 in 60000. The presence of basal cell carcinoma is much higher in whites than in blacks; 80% and 38% respectively. Odontogenic keratocyst is found in about 75% of individuals with disease and often occurs early in life. The most common skeletal abnormalities occur in the head and face, but other areas are often exposed such as ribs. The genetic mutation causing this disease occurs in PTCH genes, and PTCH products are tumor suppressors involved in cell signaling. Although the precise role of this protein in NBCCS is unknown, it is involved in signaling hedgehog pathways, which are known to control cell growth and development.
Von Hippel-Lindau's Disease
Von Hippel-Lindau (VHL) disease is a rare autosomal dominant genetic condition that affects individuals for benign and malignant tumors. The most common tumors in VHL are the central nervous system and retinal hemangioblastoma, clear cellular kidney carcinoma, pheochromocytomas, pancreatic neuroendocrine tumors, pancreatic cysts, endolymphatic sac tumors and papillary papillary epididymal cysts. VHL results from mutations in the von Hippel-Lindau tumor suppressor gene on chromosome 3p25.3.
Xeroderma pigmentosum
Xeroderma pigmentosum (XP) is an autosomal recessive disorder characterized by sensitivity to ultra-violet (UV) rays, increased risk of massive sunburn and an increased risk of skin cancer. The risk of skin cancer is more than 10,000 times that of normal people and includes many types of skin cancer, including melanoma and non-melanoma skin cancers. Also, areas exposed to sunlight from the tongue, lips and eyes have an increased risk of becoming cancerous. XP can be associated with other internal cancers and benign tumors. In addition to cancer, some of the genetic mutations that cause XP are associated with neurodegeneration. XP may be caused by a genetic mutation in 8 genes, which produces the following enzymes: XPA, XPB, XPC, XPD, XPE, XPF, XPG and Pol ?. XPA-XPF is a nucleotide excision repair enzyme that corrects the damaged DNA of UV rays and the wrong protein will allow the accumulation of mutations caused by UV rays. Pol? is a polymerase, which is an enzyme involved in DNA replication. There are many polymerase, but pol? is an enzyme that replicates the damaged DNA of UV rays. Mutations in this gene will produce damaged poles? enzymes that can not replicate DNA with UV damage. Individuals with this gene mutation have a share of XP; XP-variant disease.
fixes DNA defects and increases cancer risk
Many cancer syndromes are caused by a decrease in inheritance in the ability of DNA repair. When inherited mutations are present in DNA repair genes, repair genes will not be expressed or expressed in altered form. Then the reparation function is likely to be deficient, and, as a result, DNA damage will tend to accumulate. Such DNA damage can cause errors during DNA synthesis that cause mutations, some of which can cause cancer. DNA repair DNA mutations-lines that increase cancer risk are listed in the Table.
- Acronyms for DNA repair pathways are improvement of homologous HRR recombination, HRR sub-pathways, NHEJ non-homolog end join, BER base excision repair, TLS transcription synthesis, NER nucleotide excision repair, MMR mismatch improvement.
Genetic Filtering
Genetic tests can be used to identify mutated genes or chromosomes that are passed on from generation to generation. People who test positive have genetic mutations are not always condemned to develop cancer-related mutations, but they have an increased risk of developing cancer compared with the general population. It is recommended that people get a genetic test if their family medical history includes: Double family members with cancer, someone in their family who has cancer at a very young age or by being part of a particular ethnic group.
The genetic screening process is a simple non-invasive procedure. However, before the gene is tested for mutation, patients usually have to go to a health care provider and go through a one-on-one consultation, where they discuss the personal and family history of the cancer. Medical professionals can then assess the likelihood of patients having mutations and can guide them through a process that is a genetic filtering. It is important that this consultation be conducted because it ensures that the person provides informed consent to engage in genetic testing, realizes and understands the steps, benefits and limitations of the procedure and the more knowledgeable consequences of the hearing test results. Tests can be performed using body fluids or patient cells, these include; blood (most common), saliva, amniotic fluid and even cells from the inside of the mouth are obtained from buccal swabs. The material is then sent to a special genetic laboratory where the technician will examine it, the test results are sent back to the health care provider requesting the analysis and the results discussed with the patient.
Directly to consumer testing can be obtained without medical professionals but not recommended because consumers miss the opportunity to discuss their decisions with an educated professional. According to the National Library of Medicine in the US, genetic testing in America costs between $ 100 and $ 2000 depending on the type and complexity of the test.
Precautions
Genetic testing is important as if the test were positive out they were more aware of their own personal health and the health of close family members. With the help and advice of medical professionals, they can take steps to reduce the risk of developing cancer through:
- Regular exercise
- A healthy and balanced diet
- Maintain a healthy weight
- No smoking
- Stay safe in harmful sunlight
There is another form of precaution, an example for Hereditary Breasts and Ovarian Cancer going through surgery: Hysterectomy is the removal of all or part of the uterus, whereas a mastectomy is raised breast (a double mastectomy meaning that both breasts are removed), this can often add years to life expectancy they. Other preventive measures are routine screening and cancer screening. If a person has Lynch syndrome then they should have a routine colonoscopy to check whether there are changes in the cells lining the intestinal wall, routine examination has been shown to add an average of 7 years to the life expectancy of a suffering person. of Lynch syndrome as early detection means proper precautions and surgery can be performed more quickly. Regular breast screening is also recommended for women diagnosed with BRCA mutations, and also, recent research has shown that men with an increased risk of developing prostate cancer because BRCA mutations may decrease risk by taking aspirin. Aspirin is very useful in reducing the prevalence of cancer; However, it should be done regularly for at least five years to have any effect.
The prevalence of genetic mutations in various ethnic groups
Often genetic mutations are more common in certain ethnic groups, this is because race can trace their ancestors back to a geographical location, mutated genes are then passed down from a hereditary ancestor which is why some ethnics are more susceptible to mutations, thus increasing their likelihood of being exposed cancer [61]. As mentioned above, this can be useful because it can help health professionals assess the risk of patients having a mutation before they undergo the test. Werner's Syndrome has a prevalence of 1 in 200,000 live births in the US, but it affects individuals in Japan in 1 in 20,000-40,000 cases.
1 out of 40 Ashkenazi Jews have BRCA mutations, this is a big difference from the general population in the United States where 1 in 400 people are affected. Ashkenazi Jews are at high risk of developing hereditary breasts and ovarian cancer and it is suggested that they undergo both genetic testing to see if they have routine mutations and screening for cancer.
References
Source of the article : Wikipedia
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