Heredity and predisposition to cancer

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Heredity and predisposition to cancer: genetic factors and their influence on the risk of cancer.

I. Fundamentals of genetics and cancer: the relationship between genes, DNA and oncogenesis

  • 1.1. DNA and genome: fundamental building blocks of life:

    • 1.1.1. DNA structure: DNA (deoxyribonucleic acid) is a double spiral consisting of nucleotides. Each nucleotide consists of three components: deoxyribosis (sugar), phosphate group and nitrogen base. There are four types of nitrogenous bases: adenine (A), Timin (t), guanine (G) and cytosine (C). Adenin always connects to Timin, and guanine with cytosin, forming a pair of bases that connect two DNA chains. This complementarity provides accurate DNA replication and transmission of genetic information.
    • 1.1.2. Genom: A complete set of genetic information: The genome is a complete set of DNA of the body, including all genes and non -dodging sequences. In humans, the genome consists of approximately 3 billion pairs of bases organized in 23 pairs of chromosomes. The genome contains instructions for constructing and functioning of the body.
    • 1.1.3. Genes: units of heredity: Genes are DNA areas encoding certain proteins or functional RNA. Proteins perform a wide range of functions in the cell, including catalysis of chemical reactions, molecules, structural support and regulation of genetic expression. The number of genes in the human genome is estimated at about 20,000-25,000.
    • 1.1.4. The role of non -polling sequences: Most of the human genome (about 98%) does not encode proteins. These non -leading sequences play an important role in the regulation of genetic expression, maintaining the structure of chromosomes and other cellular processes. Many non -leading sequences contain regulatory elements, such as Enhanservers and silencers that control when and where genes are expressed.

  • 1.2. Mutations: Changes in the genetic code:

    • 1.2.1. Types of mutations: Mutations are changes in the DNA sequence. They can occur spontaneously as a result of DNA replication errors or are caused by the effects of mutagenes, such as radiation, chemicals and viruses. Mutations can be point (change of one nucleotide), deeds (removal of the DNA section), inserts (adding a DNA section), inversions (turning the DNA site) or translocations (transfer of DNA to another chromosome).
    • 1.2.2. The influence of mutations on genes: Mutations can have a different effect on genes. Some mutations do not have any influence (silent mutations), while others can change the structure or function of the protein encoded by the genome. Mutations that lead to loss of protein function are called mutations of function loss, and mutations that lead to the acquisition of a new protein function are called mutations of the acquisition of function.
    • 1.2.3. Mutations in germ and somatic cells: Mutations that occur in germ cells (spermatozoa and eggs) can be transmitted to offspring and, therefore, are hereditary. Mutations that occur in somatic cells (all other cells of the body) are not transmitted to offspring, but can contribute to the development of cancer.

  • 1.3. Genes that control the cell cycle and apoptosis:

    • 1.3.1. Proto -acting and oncogenes: Proto -acting are genes that encode proteins that contribute to the growth and division of cells. When the proto -oxogen mutates and becomes oncogen, it can contribute to uncontrolled growth and cell division, which leads to the development of cancer. Examples of oncogenes include RAS, MYC And HER2.
    • 1.3.2. Tumor Suppressors genes: Tumor-spress genes are genes that encode proteins that suppress the growth and division of cells. When the tumor-sulfight gene mutters and loses its function, cells can begin to grow and share uncontrollably, which leads to the development of cancer. Examples of tumor-soup genes include TP53, Krca1 And RB.
    • 1.3.3. Genes participating in DNA reparations: Genes involved in DNA reparations encode proteins that restore damaged DNA. When these genes mutate, cells become more susceptible to the accumulation of mutations, which can lead to the development of cancer. Examples of genes involved in DNA reparations include BRCA2, ATM And Mlh1.
    • 1.3.4. Genes regulating apoptosis: Apoptosis is a process of programmed cell death, which plays an important role in the removal of damaged or unnecessary cells. Mutations in the genes regulating apoptosis can lead to the fact that the cells that were supposed to die survive and uncontrolled, which leads to the development of cancer.

  • 1.4. Oncogenesis: A multi -stage process of cancer development:

    • 1.4.1. Accumulation of mutations: Cancer development is a multi -stage process that usually includes the accumulation of several mutations in genes that control cell growth, division and death.
    • 1.4.2. The role of epigenetic changes: Epigenetic changes are changes in genes expression that are not associated with changes in the DNA sequence. These changes may include DNA methylation and histone modification. Epigenetic changes can play an important role in the development of cancer, affecting the expression of genes that control the cell cycle, apoptosis and DNA reparation.
    • 1.4.3. The influence of environmental factors: Environmental factors, such as smoking, the effect of ultraviolet radiation and the effects of certain chemicals, can increase the risk of cancer, causing mutations in DNA or epigenetic changes.

II. Hereditary cancerous syndromes: genetic mutations transmitted from generation to generation

  • 2.1. Determination of hereditary cancer syndromes:

    • 2.1.1. Diagnostic criteria: Hereditary cancer syndrome is a genetic disease characterized by an increased risk of developing certain types of cancer. Diagnosis of hereditary cancer syndrome is based on the analysis of family history, clinical data and genetic testing results. Diagnosis criteria may include the early start of cancer, the presence of several cases of cancer in the family, the presence of rare types of cancer and the presence of certain physical characteristics associated with the syndrome.
    • 2.1.2. The share of hereditary cases of cancer: Although most cases of cancer are sporadic (that is, they are not associated with hereditary genetic mutations), approximately 5-10% of cancer cases are associated with hereditary cancer syndromes.

  • 2.2. The main hereditary cancerous syndromes:

    • 2.2.1. Heritical cancer of the breast and ovaries (HBOC):

      • 2.2.1.1. Genes Krca1 And BRCA2: This syndrome is caused by mutations in genes Krca1 And BRCA2who participate in DNA reparations. Mutations in these genes significantly increase the risk of developing breast cancer, ovarian cancer, prostate cancer and other types of cancer.
      • 2.2.1.2. The risk of cancer development: Women with mutations in genes Krca1 And BRCA2 About 50-80% have the risk of breast cancer and 20-50% risk of ovarian cancer throughout life. Men with mutations in these genes also have an increased risk of developing breast cancer and prostate cancer.
      • 2.2.1.3. Clinical manifestations: The clinical manifestations of HBOC include the early start of breast cancer (up to 50 years), the presence of breast and ovarian cancer in several family members, the presence of breast cancer in men and the presence of certain ethnic groups with a higher frequency of mutations in genes Krca1 And BRCA2 (for example, Ashkenazi Jews).
      • 2.2.1.4. Prevention and treatment strategies: HBOC prevention and treatment strategies include regular screening examinations (for example, mammography, MRI of the mammary glands, transvaginal ultrasound), preventive mastctomy (removal of mammary glands) and preventive ovariactomy (ovarian removal). Treatment of breast cancer and ovarian cancer in patients with HBOC may include surgical intervention, chemotherapy, radiation therapy and targeted therapy (for example, PARP inhibitors).

    • 2.2.2. Lynch Syndrome (hereditary non -facade colorectal cancer – HNPC):

      • 2.2.2.1. DNA reparation genes: This syndrome is caused by mutations in the genes of the DNA reparation system, such as Mlh1, MSH2, MoH6 And PMS2. These genes are involved in replication of DNA replication errors. Mutations in these genes increase the risk of developing colorectal cancer, endometrial cancer, stomach cancer, ovarian cancer and other types of cancer.
      • 2.2.2.2. The risk of cancer development: People with Lynch syndrome have approximately 80% risk of colorectal cancer in life. Women with Lynch syndrome also have a high risk of endometrial cancer.
      • 2.2.2.3. Clinical manifestations: The clinical manifestations of Lynch syndrome include the early onset of colorectal cancer (up to 50 years), the presence of several cases of colorectal cancer and/or endometrial cancer in family members, the presence of other types of cancer associated with linch syndrome, and the presence of microsatellite instability (MSI) in tumors.
      • 2.2.2.4. Prevention and treatment strategies: Strategies for the prevention and treatment of Lynch syndrome include regular colonoscopy (starting from 20-25 years), endometrial screening (for women), preventive hysterectomy (uterine removal) and salpingooportomy (removal of uterine pipes and ovaries). Treatment of cancer in patients with linch syndrome may include surgical intervention, chemotherapy and immunotherapy (especially for tumors with a high level of MSI).

    • 2.2.3. Family adenomatous polyposis (FAP):

      • 2.2.3.1. Gene APC: This syndrome is caused by mutations in the gene APCwhich is involved in the regulation of cellular growth and differentiation. Mutations in gene APC They lead to the formation of many polyps in the colon, which significantly increases the risk of developing colorectal cancer.
      • 2.2.3.2. The risk of cancer development: People with FAP, as a rule, develop colorectal cancer under the age of 40, if a preventive coloactomy is not performed (colon removal).
      • 2.2.3.3. Clinical manifestations: The clinical manifestations of FAP include the presence of hundreds or thousands of polyps in the colon, the early beginning of polyposis and colorectal cancer, the presence of other associated conditions, such as osteoma, epidermoid cysts and desmoid tumors.
      • 2.2.3.4. Prevention and treatment strategies: FAP prevention and treatment strategies include regular sigmoidoscopy (or colonoscopy) to identify and remove polyps, preventive coloctomy and monitor other possible manifestations of the syndrome.

    • 2.2.4. Li-Fraumeni syndrome (LFS):

      • 2.2.4.1. Gene TP53: This syndrome is caused by mutations in the gene TP53which is a genome of tumors. Gene TP53 plays an important role in the regulation of the cell cycle, apoptosis and DNA reparations. Mutations in gene TP53 Increase the risk of developing a wide range of types of cancer, including breast cancer, sarcoma, leukemia, brain cancer and adrenal gland cancer.
      • 2.2.4.2. The risk of cancer development: People with LFS have a very high risk of cancer in life, and often several types of cancer during life.
      • 2.2.4.3. Clinical manifestations: The clinical manifestations of LFS include the early start of cancer (up to 30 years), the presence of several types of cancer in one person, the presence of several cases of cancer in the family and the presence of rare types of cancer, such as adrenal cancer.
      • 2.2.4.4. Prevention and treatment strategies: LFS prevention and treatment strategies include regular screening for various types of cancer, avoiding radiation therapy (due to increased sensitivity to radiation) and genetic counseling.

    • 2.2.5. Multiple endocrine neoplasia (MEN):

      • 2.2.5.1. Types MEN (Men1, Men2): There are several types of MEN, each of which is associated with mutations in different genes and is characterized by the development of tumors in various endocrine glands. Men1 is associated with mutations in gene Men1and Men2 is associated with mutations in the gene RET.
      • 2.2.5.2. The risk of cancer development: The risk of cancer develops depends on the type of MEN and a specific mutation. Men1 is associated with the development of tumors of the parathyroid glands, pancreas and pituitary gland. MEN2 is associated with the development of medullary thyroid cancer, pheochromocytoma and hyperparathyroidism.
      • 2.2.5.3. Clinical manifestations: The clinical manifestations of the MEN depend on the type of MEN and affected endocrine glands.
      • 2.2.5.4. Prevention and treatment strategies: MEN prevention and treatment strategies include genetic testing, regular screening on the endocrine glands and surgical tumor removal. Preventive tyreoidctomy is recommended for people with Men2 to prevent the development of thyroid medical cancer.

    • 2.2.6. Neurofibromatosis (NF):

      • 2.2.6.1. Type NF (NF1, NF2): There are two main types of NF: NF1 and NF2. NF1 is associated with mutations in gene NF1and NF2 is associated with mutations in the gen Nf2.
      • 2.2.6.2. The risk of cancer development: NF1 is associated with an increased risk of neurofiber, gliomas, leukemia and pheochromocyte. NF2 is associated with an increased risk of development of Schvannet, meningiomas and ependim.
      • 2.2.6.3. Clinical manifestations: The clinical manifestations of NF include the presence of neurofiber (benign tumors of the nervous tissue), spots of the color “coffee with milk” on the skin, lichen nodules (pigmented spots on the iris of the eye) and other associated states.
      • 2.2.6.4. Prevention and treatment strategies: NF prevention and treatment strategies include regular monitoring for the identification and treatment of tumors, surgical removal of tumors and drug therapy (for example, cellometinib for the treatment of neurofiber plexorm).

    • 2.2.7. FON GIPPELY-LINDAU (VHL) syndrome:

      • 2.2.7.1. Gene VHL: This syndrome is caused by mutations in the gene VHLwhich is a genome of tumors. Gene VHL He plays an important role in the regulation of angiogenesis (the formation of new blood vessels). Mutations in gene VHL Increase the risk of developing hemangoblasty (tumors of the brain and spinal cord), kidney cancer, pheochromocyte and pancreatic cysts.
      • 2.2.7.2. The risk of cancer development: People with VHL have an increased risk of developing these tumors throughout life.
      • 2.2.7.3. Clinical manifestations: The clinical manifestations of VHL include hemangoblastoma, kidney cancer, pheochromocytomas and pancreatic cysts.
      • 2.2.7.4. Prevention and treatment strategies: VHL prevention and treatment strategies include regular screening for these tumors, surgical removal of tumors and targeted therapy (for example, VEGF inhibitors for treating kidney cancer).

  • 2.3. Genetic counseling and testing:

    • 2.3.1. Indications for genetic testing: Genetic testing on hereditary cancerous syndromes is recommended for people with a family history of cancer, early cancer, the presence of several types of cancer in one person and the presence of certain physical characteristics associated with the syndrome.
    • 2.3.2. Types of genetic testing: There are various types of genetic testing, including testing individual genes, panel testing (testing several genes at the same time) and sequencing of the entire exom (WES) or genome (WGS).
    • 2.3.3. Interpretation of genetic testing results: The interpretation of the results of genetic testing can be complex and requires experience in genetics and oncology. The results can be positive (a mutation in a genus associated with cancer syndrome), negative (mutation is not detected) or uncertain (a gene variant, the value of which is unclear).
    • 2.3.4. Ethical and legal aspects of genetic testing: Genetic testing raises important ethical and legal issues, such as the confidentiality of genetic information, discrimination based on genetic status and the right to information.

III. Distribution to cancer: polygenic risk and interaction of genes and the environment

  • 3.1. Polygenic risk:

    • 3.1.1. The role of many genes with a slight effect: Most cancer cases are not associated with mutations in one gene with a great effect, but are the result of the interaction of many genes with a small effect, as well as environmental factors.
    • 3.1.2. Polygenic risk scales (PRS): Polygenic risk scales (PRS) are tools that are used to assess the genetic predisposition of a person to a certain disease based on the analysis of many genetic options (single -okleotide polymorphisms – SNP). PRS summarizes the effects of many genetic options to evaluate the general genetic risk.

  • 3.2. The interaction of genes and the environment:

    • 3.2.1. Epigenetics and Cancer: Epigenetic changes can change the expression of genes in response to environmental factors, such as diet, smoking and the effects of toxins. These changes can contribute to the development of cancer.
    • 3.2.2. Environmental factors affecting the risk of cancer: Environmental factors, such as smoking, diet, obesity, exposure to ultraviolet radiation and the effect of certain chemicals, can increase the risk of cancer, interacting with a genetic predisposition.

  • 3.3. Cancer risk assessment:

    • 3.3.1. Family history: Family history is an important factor in assessing the risk of cancer. The presence of several cases of cancer in the family, especially if cancer occurs at an early age or is a rare type of cancer, may indicate an increased genetic predisposition.
    • 3.3.2. Risk assessment models: There are various models of risk assessment that are used to assess the risk of developing cancer based on family history, genetic factors and environmental factors. These models can help determine people who need more intense screening or preventive measures.

IV. The clinical significance of heredity and predisposition to cancer: screening, prevention and personalized medicine

  • 4.1. Cancer screening:

    • 4.1.1. Early detection: Early detection of cancer is a key factor in survival increase. Regular screening can help identify cancer at an early stage when it is more cured.
    • 4.1.2. Screening strategies for people with increased risk: People with an increased risk of cancer associated with hereditary cancerous syndromes or a genetic predisposition can recommend a more intense screening than for the population as a whole. This may include more frequent screening examinations, screening at an earlier age or the use of more sensitive screening methods.

  • 4.2. Cancer prevention:

    • 4.2.1. Surgical prevention: Preventive surgery, such as mastectomy (removal of mammary glands) and ovariectomy (ovarian removal), can be recommended for women with a high risk of developing breast cancer and ovarian cancer associated with mutations in genes Krca1 And BRCA2. Preventive coloactomy (removal of the colon) can be recommended to people with FAP.
    • 4.2.2. HimioProfillactics: Chemistry is the use of drugs to reduce the risk of cancer. For example, Tamoxifen and Raloxifen can be used to reduce the risk of breast cancer in women with high risk. Aspirin can be used to reduce the risk of developing colorectal cancer in people with increased risk.
    • 4.2.3. Life change change: A change in lifestyle, such as rejection of smoking, maintaining a healthy weight, using a healthy diet and regular physical exercises, can reduce the risk of developing many types of cancer.

  • 4.3. Personalized medicine:

    • 4.3.1. Target therapy: Targeted therapy is a type of cancer treatment, which is aimed at specific molecules or paths involved in the growth and spread of cancer. Genetic testing can help determine people who can be sensitive to a certain targeted therapy.
    • 4.3.2. Immunotherapy: Immunotherapy is a type of cancer treatment that uses the body’s immune system to combat cancer. Genetic factors can affect the response to immunotherapy.
    • 4.3.3. Pharmacogenomy: Pharmacogenomy is a study of the influence of genetic factors on the response to drugs. Genetic testing can help predict how a person will respond to certain drugs for cancer, and help doctors choose the most effective treatment with the least side effects.

V. New areas of research: the search for new genes, the development of new methods of diagnosis and treatment

  • 5.1. Identification of new genes related to the risk of cancer:

    • 5.1.1. Studies of full -genomic search for associations (GWAS): GWAS is used to identify genetic options associated with the risk of cancer, by analyzing a large number of people.
    • 5.1.2. New generation sequencing (NGS): NGS allows you to quickly and economically seize large areas of DNA, which facilitates the identification of new cancer genes.

  • 5.2. Development of new cancer diagnosis methods:

    • 5.2.1. Liquid biopsy: Liquid biopsy is a method of analysis of DNA, RNA or proteins circulating in the blood or other biological fluids. Liquid biopsy can be used for early detection of cancer, monitor the response of the treatment and detection of cancer relapse.
    • 5.2.2. Artificial intelligence (AI) and machine learning (MO): AI and MO are used to analyze large volumes of data (for example, images, genetic data, clinical data) to improve cancer diagnosis and predict a response to treatment.

  • 5.3. Development of new cancer treatment methods:

    • 5.3.1. Gene therapy: Gene therapy is a method of treating cancer, which includes the introduction of genes in cancer cells to destroy their or change their behavior.
    • 5.3.2. CRISPR-CAS9: CRISPR-CAS9 is a genes editing technology that allows you to accurately change the DNA sequence. CRISPR-CAS9 can be used to correct mutations in genes related to cancer, or to destroy cancer cells.
    • 5.3.3. Nanotechnology: Nanotechnologies are used to deliver drugs for cancer directly to cancer cells, minimizing side effects.

This detailed outline provides a comprehensive framework for a 100,000-word article on the topic of heredity and predisposition to cancer. It covers the essential aspects, from the basic genetic principles to the latest advancements in research and clinical applications. Each section can be expanded upon with specific examples, research findings, and clinical guidelines to create a highly informative and engaging article. This outline is designed to ensure the article meets the requirements of being well-researched, SEO-optimized, and structured for easy reading. Each numbered section represents a substantial topic that can be fleshed out with multiple paragraphs, data tables, and relevant imagery to achieve the desired word count.

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