Cancer Genetics: The role of heredity

Cancer Genetics: The role of heredity

I. Fundamentals of carcinogenesis and genetic predisposition

Cancer, contrary to common opinion, is not a single disease, but is a group of various diseases characterized by uncontrolled growth and the spread of abnormal cells. This process, known as carcinogenesis, is multi -stage and includes the accumulation of genetic and epigenetic changes in cells leading to a violation of normal mechanisms for regulating the cell cycle, apoptosis (programmable cell death) and differentiation.

Carcinogeenesis is based on genetic mutations. They can occur spontaneously as a result of errors in DNA replication or under the influence of various environmental factors, such as ultraviolet radiation, ionizing radiation, chemical carcinogens and viral infections. Mutations can affect various genes that play a key role in the control of cellular growth and division.

There are two main classes of genes, mutations in which can contribute to the development of cancer: oncogenes and tumor-soup genes.

Oncogenes – These are genes encoding proteins that stimulate cellular growth and division. Under normal conditions, these genes are strictly regulated to ensure the normal functioning of the cells. However, mutations leading to the activation of oncogenes (the so -called proto -acting) can cause uncontrolled cell growth and proliferation, which contributes to the development of the tumor. The activation of oncogenes often occurs as a result of point mutations, genes amplification (increasing the number of copies of the gene) or chromosomal translocations (moving the chromosome section to another chromosome). Examples of well -known oncogenes include RAS, MYC, ERBB2 (Her2) and Pik3ca.
Suppressors of tumors – These are genes encoding proteins that slow down cell growth and division, induce apoptosis or participate in DNA reparation. Inactivation of tumor-spress genes, as a rule, as a result of mutations, delections (loss of a chromosome section) or epigenetic changes (for example, DNA methylation), leads to the loss of their normal function. This allows cells to be uncontrollably divided and avolate, which also contributes to the development of the tumor. Examples of well-known genes of tumor-tohole genes include TP53, RB1, Krca1, BRCA2 And PTEN.

Heredity and Cancer:

Although most cases of cancer are sporadic, that is, they accidentally arise throughout a person’s life as a result of the accumulation of somatic mutations (mutations occurring in the cells of the body, except for sexuals), about 5-10% of cancer cases are due to hereditary predisposition. This means that people who have inherited certain mutations in genes associated with cancer have an increased risk of cancer during their lives.

Hereditary mutations are usually transmitted from parents to children in autosomal-dominant, autosomal-recessive or x-linked type of inheritance. The most common type is autosomal dominant inheritance, in which one copy of the mutant gene inherited from one of the parents is enough to increase the risk of cancer.

It is important to understand that the inheritance of mutation in the gene related to cancer does not mean that a person will certainly get cancer. This only means that he has increased the risk of cancer in comparison with people who do not have this mutation. The risk of developing cancer depends on many factors, including a specific inherited gene, penetrance of the mutation (the probability of the manifestation of the gene), the age of the beginning of the mutation, gender, ethnicity, lifestyle and the impact of environmental factors.

II. Genes associated with a hereditary predisposition to cancer

There are many genes in which mutations can increase the risk of various types of cancer. Below are some of the most famous and studied genes associated with a hereditary predisposition to cancer:

BRCA1 and BRCA2 (breast and ovarian cancer): Genes Krca1 And BRCA2 They are tumor consultants playing a key role in DNA reparation. Mutations in these genes significantly increase the risk of developing breast cancer, ovarian cancer, prostate cancer and pancreatic cancer. The risk of developing breast cancer in women with mutations in genes Krca1 or BRCA2 It can reach 80% by 80 years, and the risk of ovarian cancer is 40-60%. Mutations in these genes can also increase the risk of breast cancer in men.
TP53 (Li-Fraumeni syndrome): Gene TP53 It is one of the most important genes of tumors, often called the “guard of the genome.” It plays a key role in the regulation of the cell cycle, apoptosis and DNA reparations. Mutations in gene TP53 They lead to the development of li-franean syndrome, which is characterized by an increased risk of developing a wide range of cancer at an early age, including sarcoma, breast cancer, leukemia, brain cancer and adrenal gland cancer.
PTEN (COUDENS syndrome): Gene PTEN It is a genome of tumors participating in the regulation of cellular growth and proliferation. Mutations in gene PTEN They lead to the development of Cowden syndrome, which is characterized by an increased risk of developing breast cancer, thyroid cancer, endometrial cancer and gamart (benign tumors) in various organs.
MLH1, MSH2, MSH6, PMS2 (Linch syndrome): Genes MLH1, MSH2, MoH6 And PMS2 They are genes involved in DNA reparation, in particular, in reparations of unpailed bases (Mismatch Repair, MMR). Mutations in these genes lead to the development of Lynch syndrome (inheritable non -fluid colorectal cancer, HNPCC), which is characterized by an increased risk of developing colon cancer, endometrial cancer, ovarian cancer, urinary cancer, and other cancer cancer cancer.
APC (family adenomatous polyposis): Gene APC It is a genome of tumors, playing a key role in the regulation of cellular adhesion and proliferation. Mutations in gene APC They lead to the development of family adenomatous polyposis (FAP), which is characterized by the formation of multiple polyps in the colon and a high risk of developing colorectal cancer.
RET (multiple endocrine neoplasia type 2): Gene RET It is a protoncogen that encodes the tyrosinkinase receptor, which is involved in the development and differentiation of nerve cells. Mutations with the acquisition of function in gene RET They lead to the development of multiple endocrine neoplasia type 2 (Men2), which is characterized by an increased risk of developing medical thyroid cancer, pheochromocytoma and hyperparathyroidism.
VHL (Hippel-lindau disease): Gene VHL It is a genome of tumors participating in the regulation of angiogenesis (the formation of new blood vessels). Mutations in gene VHL They lead to the development of the disease of Hippel-Lindau (VHL), which is characterized by an increased risk of development of hemangoblastvost (tumors rich in blood vessels) in the brain and spinal cord, kidney cancer, pheochromocytomas and other tumors.
CDKN2A (melanoma and pancreatic cancer): Gene CDKN2a Codes two proteins: P16ink4A and P14ARF, which play a role in the regulation of the cell cycle and apoptosis. Mutations in gene CDKN2a Increase the risk of the development of melanoma and pancreatic cancer.
Chek2 (breast cancer): Gene Chek2 Codes protein participating in the control of the cell cycle and DNA reparations. Mutations in gene Chek2 They increase the risk of breast cancer, especially in women with the family history of breast cancer.
ATM (ataxia-teleangiectasia): Gene ATM Codes a protein involved in DNA reparations and the control of the cell cycle. Mutations in gene ATM They lead to the development of ataxia-teeleangiectasia, a rare genetic disease characterized by a violation of coordination of movements, telechiectasius (expanded blood vessels) and an increased risk of leukemia and lymphoma. Heterozygous carriers of mutations in gene ATM Also have an increased risk of breast cancer.

These are only some of the genes associated with a hereditary predisposition to cancer. The list is constantly expanding as new research and identify new genetic factors that contribute to the development of cancer.

III. Genetic testing of a hereditary predisposition to cancer

Genetic testing plays an important role in identifying people with a hereditary predisposition to cancer. It allows you to determine the presence of mutations in genes associated with an increased risk of cancer, and provide patients and their families with information necessary for the adoption of reasonable decisions on the prevention, early diagnosis and treatment of cancer.

Indications for genetic testing:

Genetic testing of a hereditary predisposition to cancer is recommended in the following cases:

The family history of cancer, characterized by the early start of cancer (up to 50 years), multiple cases of the same type of cancer in the family, or the presence of several different types of cancer associated with a certain genetic syndrome.
Personal history of cancer, especially breast cancer, ovarian cancer, colon cancer, endometrial cancer or melanoma diagnosed at an early age.
The presence of certain physical signs or medical conditions associated with a certain genetic syndrome that increases the risk of cancer (for example, multiple polyps in the colon with family adenomatous polyposis).
The desire to evaluate your risk of cancer and take measures to reduce it, especially if there is a family story of cancer.

Types of genetic tests:

There are several types of genetic tests used to identify mutations in genes associated with hereditary predisposition to cancer:

Unog testing: This type of testing allows you to identify mutations in one specific gene, which is supposed to be associated with an increased risk of cancer on the basis of family history or personal history.
Multigenial panel testing: This type of testing allows you to simultaneously identify mutations in several genes associated with an increased risk of developing various types of cancer. Multi -generated panel testing is becoming more and more popular, since it allows you to identify mutations in several genes at the same time, which can be more effective and economical than single -genius testing.
Testing of the entire exom (WES): This type of testing allows you to sequenate all the encoding areas of the genome (exz), which allows you to identify mutations in a wide range of genes, including genes associated with a hereditary predisposition to cancer, as well as genes associated with other genetic diseases.
Testing the entire genome (WGS): This type of testing allows to sequenate the entire genome, including coding and non -dodging areas. WGS is the most complete type of genetic testing, but it is also the most expensive and requires the greatest analysis of data.

Genetic testing process:

The process of genetic testing usually includes the following stages:

Consultation with a geneticist: Before conducting genetic testing, it is recommended to consult a geneticist or other medical specialist with experience in the field of cancer genetics. The geneticist can evaluate the family history and personal anamnesis of the patient, discuss the risks and advantages of genetic testing, help the patient choose the most suitable type of dough and interpret the test results.
Sample collection: To conduct genetic testing, it is necessary to collect a sample of the patient’s DNA. This is usually done by taking a sample of blood, saliva or smear from the inside of the cheek.
DNA analysis: A DNA sample is sent to a genetic laboratory for analysis. In the laboratory, DNA is allocated from the sample and sequencing of genes of interest.
Interpretation of the results: After the DNA analysis is completed, the genetic laboratory provides a report with test results. A geneticist or other medical specialist interprets the test results and discusses them with the patient.

Genetic test results:

The results of genetic testing can be:

Positive: A positive result means that the patient has a mutation in a gene associated with an increased risk of cancer.
Negative: A negative result means that the patient does not reveal mutations in genes tested within the framework of this test. However, the negative result does not exclude completely the risk of cancer, since there are many other genetic and environmental factors that can contribute to the development of cancer.
Indefinite (option with an indefinite value, VUS): An indefinite result means that the patient has an option in a gene related to cancer, but his influence on the risk of cancer is not known. In such cases, additional testing or observation may be required.

The consequences of genetic testing:

The results of genetic testing may have significant consequences for the patient and his family. A positive result may provide the information necessary for the adoption of reasonable decisions on the prevention, early diagnosis and treatment of cancer.

Preventive measures:

The following preventive measures can be recommended to people with positive results of genetic testing:

More frequent screening examination: Regular screening examinations (for example, mammography, colonoscopy) can help identify cancer at an early stage when it is more treated.
Preventive surgery: In some cases, for example, with mutations in genes Krca1 or BRCA2Preventive surgery can be recommended, such as mastectomy (removal of the mammary gland) or ovariectomy (ovarian removal), to reduce the risk of breast cancer or ovarian cancer.
HimioProfillactics: In some cases, drugs can be prescribed to reduce the risk of cancer (for example, tamoxifen to reduce the risk of breast cancer).
Life change change: A healthy lifestyle, including a balanced diet, regular physical exercises and smoking, can help reduce the risk of cancer.

Recommendations for the family:

The results of genetic testing can also be important for family members, since they can be carriers of the same mutation and, therefore, have an increased risk of cancer. Family members are recommended to undergo genetic counseling and, if necessary, genetic testing to evaluate their risk of cancer.

Ethical and social aspects of genetic testing:

Genetic testing is associated with a number of ethical and social aspects that must be taken into account:

Confidentiality: The results of genetic testing should be confidential and protected from unauthorized access.
Discrimination: There is a risk of discrimination based on genetic information, for example, from employers or insurance companies. In some countries, there are laws that protect people from genetic discrimination.
Psychological impact: The results of genetic testing can have a significant psychological effect on patients and their family. It is important to provide patients with support and consultations in order to help them cope with the emotional consequences of genetic testing.
Validity: It is important that genetic testing is carried out only if there are appropriate indications with the consent of the patient.

IV. Directions of research in the field of cancer genetics

The area of cancer genetics is actively developing, and at present, numerous studies are being conducted aimed at improving the understanding of genetic factors that promote cancer development, and the development of new strategies for the prevention, diagnosis and treatment of cancer.

Some of the most promising areas of research include:

Identification of new cancer genes: Studies on sequencing of the entire genome and the entire exomic allow you to identify new genes, mutations in which can increase the risk of cancer.
Studying the mechanisms of action of known genes related to cancer: Understanding of the mechanisms of action of genes, such as Krca1, TP53 And MLH1can help develop new therapeutic strategies aimed at restoring their normal function or aimed at the path that they regulate.
Development of new genetic testing methods: New genetic testing methods are being developed, which are faster, cheap and accurate than existing methods.
Personalized medicine: Genetic information can be used to develop personalized approaches to the prevention, diagnosis and treatment of cancer. For example, on the basis of the genetic profile of the tumor, you can choose the most effective treatment for a particular patient.
Gene therapy: Gene therapy is a treatment method in which genes are used to treat or prevent diseases. Currently, genetic therapy is studied as a potential method for treating cancer, for example, to restore the function of tumor genes or to enhance the immune response to the tumor.
Immunotherapy: Immunotherapy is a treatment method in which the patient’s immune system is used to combat cancer. Genetic information can be used to develop more effective immunotherapeutic strategies, for example, to identify tumor antigens, which can be used to aim immune cells per tumor.

Studies in the field of cancer genetics have great potential for improving the health and well -being of people around the world. Improving the understanding of the genetic factors contributing to the development of cancer will develop more effective strategies for the prevention, early diagnosis and treatment of cancer, which will lead to a decrease in incidence and mortality from this disease.

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