Heredity and predisposition to cancer

Heredity and predisposition to cancer: genetic risk factors and the possibility of prevention

I. Fundamentals of cancer genetics: from DNA to tumor

A. The role of DNA in the regulation of cellular growth and division:

1. DNA structure and coding of genetic information: DNA, deoxyribonucleic acid, is the basis of the genetic information of the body. It consists of two intertwined threads forming a double spiral. Each thread consists of nucleotides, including sugar (deoxybosis), phosphate group and nitrogen base. There are four types of nitrogenous bases: adenin (A), guanine (G), cytosine (C) and Timin (t). The sequence of these bases determines the genetic code.

2. Genes as a unit of heredity: Genes are DNA areas that encode certain proteins. Proteins perform many functions in the cell, including catalysis of chemical reactions (enzymes), structural support (cytoskeleton), transport transport and regulation of the expression of other genes. Each person has two copies of each gene inherited from parents.

3. Replication, transcription and broadcasting processes: DNA replication is the DNA doubling process before dividing the cell. Transcription is the process of RNA synthesis (ribonucleic acid) based on DNA matrix. Broadcast is a process of protein synthesis based on RNA matrix. These processes ensure the transfer of genetic information from DNA to proteins that determine the function of the cell.

4. The cell cycle and the mechanisms of its regulation: The cell cycle is a sequence of events taking place in a cage from one division to the next. It includes growth phases (G1 and G2), DNA replication (S) and division (M). The cell cycle is regulated by many proteins that control the progression of the cell through various phases of the cycle. Control points in the cellular cycle provide verification of the correctness of DNA replication and other processes, preventing cell division with damaged DNA.

B. Mutations as a source of genetic changes:

1. Types of mutations: point mutations, deletions, inspections, translocations: Mutations are changes in the DNA sequence. They can be caused by various factors, including replication errors, the effect of chemicals or radiation. Point mutations are changes in one nucleotide. Deletions are the loss of DNA sections. Inersion is inserts of additional DNA sections. Translocations are the movement of DNA areas between different chromosomes.

2. Causes of mutations: spontaneous mutations, mutagenes (chemicals, radiation, viruses): Spontaneous mutations arise as a result of errors in the process of DNA replication. Mutagens are factors that increase the frequency of mutations. Chemicals, such as benzene and formaldehyde, can damage DNA. Radiation, including ultraviolet and ionizing radiation, can also cause mutations. Some viruses, such as the human papillomavirus (HPV), can be built into cell DNA and cause mutations.

3. The influence of mutations on the functions of genes and proteins: Mutations can affect the functions of genes and proteins in various ways. Some mutations lead to the synthesis of non -functional proteins. Other mutations can change the activity of proteins or their interaction with other molecules. The influence of mutation depends on its type and location in the gene.

4. Mutations in somatic and germinal cells: consequences for the body and offspring: Mutations in somatic cells (body cells) affect only the body in which they occurred. Mutations in the germ cells (germ cells) can be transmitted to offspring. Hereditary mutations in cancer genes can significantly increase the risk of cancer in descendants.

C. Oncogen and tumor sepressors: key cells of cellular growth:

1. Oncogenes: functions and activation mechanisms: Oncogenes are genes that contribute to uncontrolled growth and cell division. They are often mutated forms of normal genes called proto -acting. ProtooCogenes participate in the regulation of the cell cycle, apoptosis (programmable cell death) and differentiation. Activation of oncogenes can occur as a result of mutations, genes amplification (increasing the number of copies of the gene) or translocations.

2. Tumors-Suppressors genes: functions and inactivation mechanisms: Tumor-soup genes are genes that suppress cellular growth and division. They act as brakes in the cell cycle. The inactivation of tumor-soup genes can occur as a result of mutations, delections or epigenetic changes (changes in the expression of genes that are not associated with a change in the sequence of DNA).

3. The interaction of oncogenes and genes of tumors in the development of cancer: The development of cancer is often associated with the activation of oncogenes and the inactivation of tumor-soup genes. The activation of oncogenes leads to the acceleration of cellular growth, and the inactivation of tumor-soup genes relieves the brakes from cell division. As a result, the cells begin to multiply uncontrolled, which can lead to the formation of a tumor.

4. Examples of well-known oncogenes (RAS, MyC) and tumor-genes (TP53, BRCA1/2):

   • RAS: The RAS genes family encodes proteins involved in the transmission of signals from receptors on the surface of the cage to the core, adjusting cell growth and differentiation. Mutations in RAS genes are often found with lung cancer, colon cancer and pancreatic cancer.
   • MYC: The Myc gene encodes a transcription factor that regulates the expression of many genes involved in cell growth, proliferation and apoptosis. Activation of the Myc gene is often observed for lymphomas, breast cancer and lung cancer.
   • TP53: The TP53 gene encodes a protein that plays an important role in the control of the cell cycle, apoptosis and DNA reparations. Mutations in the TP53 gene are found for most types of cancer.
   • BRCA1/2: BRCA1 and BRCA2 genes encode proteins involved in DNA reparations. Mutations in these genes significantly increase the risk of developing breast cancer, ovarian cancer and other types of cancer.

D. The role of epigenetic changes in the development of cancer:

1. DNA methylation and histone modification: Epigenetic changes are changes in the expression of genes that are not associated with a change in the sequence of DNA. DNA methylation is the addition of a methyl group to cytosin in DNA. DNA methylation can suppress genes. Modifications of histones are changes in histone proteins that pack DNA in the cage nucleus. Histonian modifications can affect the availability of DNA for transcription.

2. The influence of epigenetic changes on the expression of oncogenes and tumor-soup genes: Epigenetic changes can affect the expression of oncogen and tumor-genes. DNA methylation can suppress the expression of tumor-soup genes, and histone modifications can activate the expression of oncogenes.

3. Epigenetic changes as potential targets for cancer therapy: Epigenetic changes are reversible, which makes them potential targets for cancer treatment. Preparations are developed that can inhibit DNA methylation or histone modification, restoring the normal expression of genes in cancer cells.

II. Hereditary predisposition to cancer: genetic syndromes and risks

A. What is hereditary cancer and how it differs from sporadic cancer:

1. Determination of hereditary cancer: Hereditary cancer is a cancer that occurs as a result of inheritance of a mutation in a gene that increases the risk of cancer. Hereditary cancer is about 5-10% of all cases of cancer.

2. Sporadic cancer: the role of acquired mutations: Sporadic cancer is cancer that occurs as a result of acquired mutations in somatic cells. Sporadic cancer is most cancer cases. Acquired mutations can be caused by various factors, including the effects of mutagenes, DNA replication errors and age -related changes.

3. Key differences in hereditary and sporadic cancer: age age, multiplicity of tumors, family history:

   • Age of the beginning: Hereditary cancer is often developing at a younger age than sporadic cancer.
   • Multiple of tumors: In people with hereditary cancer, several tumors are more often observed, both in one organ and in different organs.
   • Family history: Hereditary cancer is characterized by the presence of cases of cancer in the family, especially in close relatives.

B. The main genetic syndromes associated with an increased risk of cancer development:

1. Li-frane syndrome (mutations in the TP53 gene): Lee-frane syndrome is a rare hereditary syndrome associated with mutations in the TP53 gene. People with Li-Franean syndrome have a significantly increased risk of developing various types of cancer, including breast cancer, soft tissue sarcoma, leukemia, brain cancer and adrenal cancer. The risk of developing cancer during their lives in people with Li-Frameni syndrome is about 90%.

2. Hereditary breast cancer and ovary (mutations in the genes of BRCA1 and BRCA2): Mutations in the BRCA1 and BRCA2 genes significantly increase the risk of developing breast cancer and ovarian cancer. Women with a mutation in the BRCA1 gene have about 70% risk of breast cancer and about 40% risk of ovarian cancer throughout life. Women with a mutation in the BRCA2 gene have about 50% risk of breast cancer and about 20% risk of ovarian cancer throughout life. Men with mutations in the BRCA1 and BRCA2 genes also have an increased risk of developing breast cancer, prostate cancer and other types of cancer.

3. Lynch syndrome (mutations in the genes of the DNA reparation system: Mlh1, MSH2, MSH6, PMS2): Lynch syndrome is a hereditary syndrome associated with mutations in the genes of the DNA reparation system. People with Lynch syndrome have a significantly increased risk of developing colon cancer, endometrial cancer, stomach cancer, ovarian cancer and other types of cancer. The risk of developing colon cancer during life in people with Lynch syndrome is about 80%.

4. Family adenomatous polyposis (mutations in the APC gene): Family adenomatous polyposis (SAP) is a hereditary syndrome associated with mutations in the APC gene. People with SAP develop hundreds or thousands of polyps in the colon, which can develop into colon cancer if they are not removed. The risk of developing colon cancer during life in people with SAP is approaching 100%if the preventive coloactomy (colon removal) is not carried out.

5. Multiple endocrine neoplasia (Maine) types 1 and 2 (mutations in the Men1 and RET genes): Multiple endocrine neoplasia (Maine) is a group of hereditary syndromes associated with the development of tumors in several endocrine glands. Maine type 1 is associated with mutations in the Men1 gene and is characterized by the development of tumors in parathyroid glands, pancreas and pituitary gland. Maine 2 is associated with mutations in the RET gene and is characterized by the development of medullary thyroid cancer, pheochromocytoma and hyperparathyroidism.

6. Neurofibromatosis of types 1 and 2 (mutations in the genes NF1 and NF2): Neurofibromatosis (NF) is a group of hereditary syndromes associated with the development of tumors in the nervous system. Type 1 NF is associated with mutations in the NF1 gene and is characterized by the development of neurofiber (tumors from Schwann cells), spots of the color of “coffee with milk” on the skin and other manifestations. Type 2 NF is associated with mutations in the NF2 gene and is characterized by the development of the Swann (auditory nerve tumors), meningiomas and ependim.

C. Risk assessment of hereditary cancer: family history and genetic counseling:

1. The importance of collecting a detailed family history: The collection of detailed family history is an important step in assessing the risk of hereditary cancer. It is necessary to find out whether there have been cases of cancer in close relatives (parents, brothers, sisters, children, grandfathers and grandmothers), the type of cancer, the age of the onset of cancer and other factors.

2. Criteria for referring to genetic counseling: There are certain criteria that indicate the need to send a person to genetic counseling. These include:

   • The early age of the start of cancer (up to 50 years).
   • The presence of several cases of cancer in one person.
   • The presence of cancer cases associated with a certain genetic syndrome (for example, breast cancer and ovarian cancer in one woman).
   • The presence of cancer cases in several generations of the family.
   • The presence of rare types of cancer (for example, medullary cancer).
   • Belonging to a certain ethnic group with an increased risk of hereditary mutations (for example, Ashkenazi Jews with mutations in BRCA1 and BRCA2 genes).

3. The process of genetic counseling: risk assessment, discussion of testing options, interpretation of results: Genetic counseling includes an assessment of the risk of hereditary cancer based on a family history and other factors, a discussion of genetic testing options (if necessary), the interpretation of genetic testing results and the development of a prevention and observation plan.

4. Genetic testing: Types of tests, advantages and restrictions, ethical questions: Genetic testing allows you to identify the presence of mutations in genes associated with an increased risk of cancer. There are various types of genetic tests, including tests for one gene and multiprophen panels. The advantages of genetic testing include the possibility of identifying people with an increased risk of cancer, which allows for preventive measures and early diagnosis. Genetic testing restrictions include the possibility of obtaining false negative or false positive results, as well as detecting mutations with an indefinite clinical value. Ethical issues related to genetic testing include issues of confidentiality, discrimination and psychological impact of results.

D. Preventive measures for people with an increased risk of hereditary cancer:

1. Regular examinations and screening: Regular examinations and screening are an important part of cancer prevention in people with an increased risk of hereditary cancer. Screening can include mammography, mRI of breasts, colonoscopy, endoscopy of the stomach, ovarian ultrasound and other types of examinations, depending on the type of cancer to which a person has increased risk.

2. Preventive operations (mastractomy, ovariectomy, coloctomy): Preventive operations can reduce the risk of cancer in people with an increased risk of hereditary cancer. Preventive mastectomy (breast removal) can significantly reduce the risk of developing breast cancer in women with mutations in BRCA1 and BRCA2 genes. Preventive ovariectomy (ovarian removal) can reduce the risk of ovarian cancer and breast cancer in women with mutations in BRCA1 and BRCA2 genes. Preventive coloactomy (removal of the colon) can prevent the development of colon cancer in people with family adenomatous polyposis (SAP).

3. Chemoprophylaxis (tamoxifen, raloxifen): Chemistry is the use of drugs to reduce the risk of cancer. Tamoxifen and Raloxifen are selective estrogen receptor modulators (SERM), which can reduce the risk of breast cancer in women with increased risk.

4. Change in lifestyle (healthy nutrition, physical activity, rejection of smoking): A change in lifestyle can reduce the risk of cancer in people with an increased risk of hereditary cancer. Healthy nutrition, rich in fruits, vegetables and whole grains, physical activity and smoking refusal can reduce the risk of developing many types of cancer.

III. Genetic predisposition to cancer: genes polymorphism and interaction with environmental factors

A. Genes polymorphisms: genes that affect the risk of cancer:

1. Definition of polymorphism gene: Gene polymorphism is a variation in the DNA sequence, which is found in a population with a frequency of at least 1%. Genes polymorphisms can affect the function of the gene and the risk of developing various diseases, including cancer.

2. Types of polymorphisms: one -toned polymorphisms (SNP), inserts/deeds (Indel): One -okleotide polymorphism (SNP) is changes in one nucleotide in the DNA sequence. Inserts/deletions are inserts or deletions of short DNA sections.

3. Mechanisms of the influence of polymorphisms on the risk of cancer: changes in genes expression, structure and protein function: Genes polymorphisms can affect the risk of cancer in various ways. They can change the expression of genes, the structure and function of proteins. For example, polymorphism in the promoter region of the gene can affect the level of gene expression. Polymorphism in the encoding area of ​​the gene can change the amino acid sequence of protein, which can affect its function.

4. Examples of polymorphisms of genes related to the risk of cancer development:

   • Polymorphisms in the genes of metabolism of carcinogens (CYP1A1, GSTM1): CyP1A1 and GSTM1 genes encode enzymes involved in carcinogens metabolism. Polymorphisms in these genes can affect the body’s ability to process and remove carcinogens, which can affect the risk of lung cancer, bladder cancer and other types of cancer.
   • Polymorphisms in DNA reparation genes (XRCC1, OGG1): XRCC1 and OGG1 genes encode proteins involved in DNA reparations. Polymorphisms in these genes can affect the body’s ability to restore damaged DNA, which can affect the risk of developing breast cancer, lung cancer and other types of cancer.
   • Polymorphisms in the genes of the immune system (IL10, TNFα): IL10 and TNFα genes encode the cytokines involved in the regulation of the immune response. Polymorphisms in these genes can affect the body’s ability to fight cancer cells, which can affect the risk of developing stomach cancer, colon cancer and other types of cancer.

B. The interaction of genes and the environment: the role of environmental factors in the development of cancer in people with a genetic predisposition:

1. Environmental factors that increase the risk of cancer: smoking, nutrition, exposure to chemicals, radiation, infection:

   • Smoking: Smoking is the main risk factor for the development of lung cancer, bladder cancer, laryngeal cancer, esophagus cancer and other types of cancer.
   • Nutrition: Unhealthy nutrition, rich in fats, red meat and treated foods, can increase the risk of developing colon cancer, breast cancer and other types of cancer. The lack of fruits and vegetables in the diet can also increase the risk of cancer.
   • The effect of chemicals: The effect of some chemicals, such as asbestos, benzene and formaldehyde, can increase the risk of lung cancer, mesotheliomas, leukemia and other types of cancer.
   • Radiation: The effect of ionizing radiation (for example, with x -ray studies or radiation therapy) can increase the risk of leukemia, thyroid cancer and other types of cancer. Ultraviolet radiation (for example, from the sun or solariums) can increase the risk of skin cancer.
   • Infections: Some infections, such as human papillomans (HPV), hepatitis B virus (HMV) and Helicobacter Pylori, can increase the risk of developing cervix, liver cancer and stomach cancer, respectively.

2. Geno-medium interactions: as a genetic predisposition affects susceptibility to environmental factors: Geno-environmental interactions is the interaction between genes and environmental factors, which affects the risk of cancer. In people with a genetic predisposition to cancer, the influence of certain environmental factors can significantly increase the risk of cancer.

3. Examples of geno-medium interactions: smoking and polymorphisms in the genes of metabolism of carcinogens, diet and polymorphisms in the genes of the immune system:

   • Smoking and polymorphisms in the genes of metabolism of carcinogens: In people with certain polymorphisms in the genes of metabolism of carcinogens (for example, CYP1A1 and GSTM1), smoking can significantly increase the risk of lung cancer.
   • Diet and polymorphisms in the genes of the immune system: In people with certain polymorphisms in the genes of the immune system (for example, IL10 and TNFα), an unhealthy diet can increase the risk of developing colon cancer.

4. Preventive strategies taking into account geno-medium interactions: personalized recommendations on the lifestyle and nutrition: Accounting for geno-medium interactions can allow you to develop personalized recommendations on the lifestyle and nutrition, which will help reduce the risk of cancer in people with a genetic predisposition. For example, people with certain polymorphism in the genes of metabolism of carcinogens are recommended to avoid smoking and other sources of exposure to carcinogens. People with certain polymorphisms in the genes of the immune system are recommended to adhere to a healthy diet rich in fruits, vegetables and whole grains.

IV. Future of cancer genetics: personalized medicine and new methods of diagnosis and treatment

A. The role of genetics in personalized medicine:

1. Identification of genetic markers to predict the risk of cancer and response to treatment: Genetics plays an important role in personalized medicine, allowing you to identify genetic markers that can help predict the risk of cancer and response to treatment.

2. Development of targeted therapy based on the genetic characteristics of the tumor: Targeted therapy is a type of cancer treatment that is aimed at certain molecules involved in the growth and spread of cancer cells. The genetic features of the tumor can help determine which molecules are most important for tumor growth, and choose the most effective targeted drugs.

3. Pharmacogenetics: the effect of genetic variations on metabolism and the effectiveness of drugs: Pharmacogenetics studies the effect of genetic variations on metabolism and the effectiveness of drugs. Genetic variations can affect how the body processes drugs, which can affect the effectiveness and side effects of the drug. Pharmacogenetic testing can help doctors choose the most effective dose of the drug for each patient, minimizing side effects.

4. Advantages and challenges of personalized medicine: The advantages of personalized medicine include the possibility of more accurate diagnosis, predicting the risk of cancer and response to treatment, as well as the development of more effective and safe treatment methods. The calls of personalized medicine include the high cost of genetic testing, the need to develop new targeted drugs and resolve ethical issues related to genetic information.

B. New cancer diagnosis methods based on genetic technologies:

1. Liquid biopsy: detection of circulating tumor cells (TsOC) and DNA of the tumor in the blood: Liquid biopsy is a cancer diagnosis method, which allows you to detect circulating tumor cells (TsOC) and DNA of the tumor in the blood. Liquid biopsy can be used for early diagnosis of cancer, monitor a response to treatment and detection of resistance to therapy.

2. Genomic sequencing of the tumor: Identification of mutations and other genetic changes in cancer cells: Genomic sequencing of a tumor is a method that allows you to determine the sequence of DNA in cancer cells. Genomic sequencing of the tumor can identify mutations and other genetic changes that can help in choosing the most effective therapy.

3. Development of new biomarkers for early diagnosis and prediction of the outcome of the disease: Biomarkers are substances that can be measured in the blood, urine or other biological fluids and which may indicate the presence of cancer or other diseases. New biomarkers are developed, which can be used for early diagnosis of cancer and predicting the outcome of the disease.

C. New directions in the treatment of cancer based on genetic knowledge:

1. Immunotherapy: activation of the immune system to combat cancer cells: Immunotherapy is a type of cancer treatment that activates the immune system to combat cancer cells. Immunotherapy can be effective for the treatment of certain types of cancer, but it does not work for all patients. Genetic factors can affect how well the patient will respond to immunotherapy.

2. CRISPR-CAS9 and other genes editing methods: Correction of genetic defects in cancer cells: CRISPR-CAS9 is a genes editing technology that allows you to accurately change the DNA sequence. CRISPR-CAS9 can be used to correct genetic defects in cancer cells, which can lead to their death or reduce their ability to growth and spread.

3. Development of cancer vaccines aimed at specific mutations in cancer cells: Vaccines are developed against cancer, which are aimed at specific mutations in cancer cells. These vaccines can help the immune system recognize and destroy cancer cells containing these mutations.

D. Ethical and social aspects of genetic testing and personalized medicine in oncology:

1. Confidentiality and protection of genetic information: Privacy and protection of genetic information are important ethical aspects of genetic testing and personalized medicine in oncology. It is necessary to ensure that the genetic information of patients is not used for discrimination or other unlawful purposes.

2. The availability of genetic testing and personalized therapy for all patients: The availability of genetic testing and personalized therapy for all patients is an important social task. It is necessary to ensure that all patients, regardless of their socio-economic status, have the opportunity to access these advanced technologies.

3. Psychological impact of genetic testing results: informed consent and psychological support: The results of genetic testing can have a significant psychological effect on patients and their family. It is necessary to ensure that patients receive informed consent to genetic testing and have access to psychological support after obtaining results.

4. Regulation and standardization of genetic testing and personalized therapy: It is necessary to develop clear rules and standards for genetic testing and personalized therapy in order to ensure their quality and safety.

This detailed outline provides a comprehensive foundation for your 100,000-word article. Each section can be expanded upon with in-depth explanations, research findings, clinical examples, and relevant statistics. Remember to cite your sources appropriately and maintain a consistent tone and style throughout the article. Good luck!