Hereditary predisposition to cancer

hereditary cancer

The term “cancer” covers more than 100 different diseases, the main characteristic of which is uncontrolled and abnormal cell division. A collection of these cells forms abnormal tissue called a tumor.

Some forms of cancer, such as blood cancer, do not form a tumor mass.

Tumors can be benign (non-cancerous) or malignant (cancerous). Benign tumors can grow, but they are unable to spread to distant parts of the body and usually do not threaten the patient’s life. During their growth, malignant tumors penetrate into surrounding organs and tissues and are able to spread through the blood and lymph to distant parts of the body (metastasize).

Some types of malignant tumors can affect the lymph nodes. Lymph nodes are normally tiny, bean-shaped structures. Their main function is to filter the flow of lymph passing through them and cleanse it, which is of great importance in the functioning of the body’s immune defense.

Lymph nodes are located in clusters in various parts of the body. For example, on the neck, axillary and groin areas. Malignant cells separated from the tumor can travel throughout the body through the blood and lymph flow, settling in the lymph nodes and other organs and giving rise to new tumor growth there. This process is called metastasis.

A metastatic tumor is called by the name of the organ where it originated, for example, if breast cancer has spread to lung tissue, then it is called metastatic breast cancer, not lung cancer.

Malignant cells can originate anywhere in the body. A tumor is named according to the type of cells from which it originates. For example, the name “carcinoma” is given to all tumors formed from skin cells or tissue covering the surface of internal organs and gland ducts. “Sarcomas” originate from connective tissue such as muscle, fat, fibrous, cartilage or bone.

Cancer statistics

After diseases of the cardiovascular system, cancer is the 2nd most common cause of death in developed countries. The average 5-year survival rate after a cancer diagnosis (regardless of location) is currently about 65%.

The most common types of cancer, excluding basal cell and squamous skin cancer, which are widespread in old age, are breast, prostate, lung and colon cancer.

Despite the fact that the incidence of certain types of tumors varies somewhat in different countries, almost everywhere in developed countries, lung, colon, breast and pancreas cancer, as well as prostate cancer are the 5 most common causes of death from cancer.

Lung cancer remains the leading cause of cancer deaths, and the majority of these deaths are caused by smoking. Over the past decade, mortality from lung cancer among men has begun to decline, but there has been an increase in the incidence of lung cancer among women.

Risk factors in oncology

“Risk factors” include any circumstances that increase the likelihood of a particular person developing the disease. Some risk factors can be controlled, such as tobacco smoking or certain infections. Other risk factors, such as age or ethnicity, cannot be controlled.

Although many risk factors are known that can influence the occurrence of cancer, for most of them it is not yet clear whether one or another factor can cause the disease alone or only in combination with other risk factors.

Increased risk of developing cancer

Understanding your individual risk of developing cancer is important. Those patients whose families have had cases of illness or death from cancer, especially at a young age, are at increased risk. For example, a woman whose mother or sister had breast cancer has twice the risk of developing breast cancer compared to those without a family history of the disease.

Those patients with a family history of increased incidence of cancer should begin regular screening examinations at a younger age and undergo them more often. Patients with an established genetic syndrome that runs in the family can undergo special genetic testing, based on which the individual risk for each family member will be determined.

Genetics hand

The ancient Greeks believed that the cause of cancer was an excess of one of the vital moistures, which they called “black bile.” Medicine of the 17th and 18th centuries saw the cause of cancer development in the penetration of parasites into the body.

Today, much more has become understood about the relationship between cancer occurrence and genetic changes. Viruses, ultraviolet radiation, chemical agents and many other things can damage a person’s genetic material, and if certain genes are affected, a person can develop cancer. In order to understand which specific genes are damaged and can initiate cancer, and how this happens, it is necessary to obtain a basic knowledge of genes and genetics.

Genes

is a tiny and compactly packaged substance located in the very center of any living cell – in its nucleus.

They are a functional and physical carrier of information that is transmitted from parents to children. Genes control most of the processes that occur inside the body. Some genes are responsible for such appearance traits as eye or hair color, others for blood type, but there is a group of genes responsible for the development (or rather, non-development) of cancer. Some genes have a protective function against the occurrence of “cancerous” mutations.

Genes are made up of sections of deoxyribonucleic acid (DNA) and are located inside special bodies called “chromosomes” found in every cell of the body.

Genes encode information about the structure of proteins. Proteins perform their own specific functions in the body: some promote cell growth and division, others are involved in protecting against infections. Each cell in the human body contains about 30 thousand genes, and based on each gene, its own protein is synthesized, which has a unique function.

Hereditary information about diseases in chromosomes

Normally, each cell of the body contains 46 chromosomes (23 pairs of chromosomes). A person receives some genes on each chromosome from his mother, and others from his father. Pairs of chromosomes 1 to 22 are numbered sequentially and are called “autosomal.” The 23rd pair, which are called “sex chromosomes,” determines the sex of the child being born. The sex chromosomes are called “X” (“X”) and “Y” (“Y”). Girls have two “X” chromosomes in their genetic set, and boys have “X” and “Y”.

Genes and cancer

When working normally, genes support normal cell division and growth. When damage occurs in genes—a “mutation”—cancer can develop. A mutated gene causes the cell to produce an abnormal, malfunctioning protein. This abnormal protein in its action can be either useful for the cell or indifferent and even dangerous.

Two main types of gene mutations may occur.

• If a mutation can be passed from one parent to a child, then it is called “germinogenic.” When such a mutation is passed from parents to child, it is present in every cell of that child’s body, including the cells of the reproductive system – sperm or eggs. Since such a mutation is contained in the cells of the reproductive system. It is passed on from generation to generation. Germ mutations are responsible for the development of less than 15% of malignant tumors. Such cases of cancer are called “familial” (that is, passed on in families) forms of cancer.
• Most cases of malignant tumors develop as a result of a series of genetic mutations that occur throughout the life of an individual. Such mutations are called “acquired” because they are not congenital. Most acquired mutations are caused by environmental factors, such as exposure to toxins or cancer-causing agents. The cancer that develops in these cases is called “sporadic.” Most scientists are of the opinion that for a tumor to occur, a number of mutations in several genes in a certain group of cells are necessary. Some people may carry a higher number of inherited mutations in their cells than others. Thus, even under equal environmental conditions, when exposed to the same amount of toxins, some people have a higher risk of developing cancer.

Tumor suppressor genes and oncogenes

There are two main types of genes known, mutations in which can cause the development of cancer – these are “tumor suppressor genes” and “oncogenes”.

Suppressor genes tumors have protective properties. Normally, they limit cell growth by controlling the number of cell divisions, the restoration of damaged DNA molecules, and timely cell death. If a mutation occurs in the structure of a tumor suppressor gene (due to congenital causes, environmental factors, or the aging process), the cells are able to grow and divide uncontrollably and may eventually form a tumor. About 30 tumor suppressor genes are known in the body today, including the BRCA1, BRCA2, and p53 genes. It is known that about 50% of all malignant tumors develop with the participation of a damaged or completely lost p53 gene.

Oncogenes are mutated versions of proto-oncogenes. Under normal conditions, proto-oncogenes determine the number of division cycles that a healthy cell can survive. When a mutation occurs in these genes, the cell gains the ability to quickly and indefinitely divide, a tumor is formed due to the fact that nothing limits cell growth and division. To date, several oncogenes have been well studied, such as “HER2/neu” and “ras”.

Several genes are involved in the development of a malignant tumor

For cancer to develop, mutations in several genes in one cell must occur, which upsets the balance of cell growth and division. Some of these mutations may be hereditary and already pre-exist in the cell, while others may occur during a person’s life. Different genes can interact unpredictably with each other or with environmental factors, ultimately leading to cancer.

Based on current knowledge of tumor pathways, new approaches to cancer control are being developed to reverse the effects of mutations in tumor suppressor genes and oncogenes. Every year new genes involved in the formation of tumors are studied.

Family medical history

“Family Tree” provides visual information about representatives of different generations of a family and their family relationships. Knowing your family’s medical history can help your family doctor understand what hereditary risk factors run in your family. Genetic testing can, in some cases, make it possible to accurately predict a person’s risk of developing a tumor, but a family medical history can also be very helpful in making the most accurate prognosis. This is because family medical history reflects a broader picture than the range of genes being studied, as additional risk factors such as environment, behavioral habits and cultural background influence the health of family members.

For families in which there is an increased incidence of cancer, researching medical ancestry can be an important step towards prevention and early diagnosis of the disease. In an ideal situation, this could reduce the risk of disease by changing the habits and lifestyle of an individual who has a negative hereditary factor. For example: quitting smoking, changing everyday habits towards a healthy lifestyle, regular physical activity and a balanced diet – all this has a certain preventive value. It is important to note that even the presence of risk factors (that is, any factors that increase the risk of developing cancer) of cancerous tumors does not mean with a 100% probability that an individual will develop cancer, it only means that he should be aware of his increased risk of developing cancer. .

Be open with your family when discussing the problem

If you have been diagnosed with cancer, do not hesitate to discuss your problem with family members, this may help them understand the need for regular health checks, such as mammography or colonoscopy, as a strategy for early detection and complete cure of the disease. Share with your family information about your treatment, the medications you are taking, the names and specialties of your treating doctors and the clinic where you are receiving treatment. In the event of a health emergency, this information can be life-saving. At the same time, learning more about your family’s medical history can be helpful for your own treatment.

How to collect your family’s medical history?

Whatever path you take, you should remember that the most informative and useful medical history is the one that is collected as thoroughly and thoroughly as possible. Information is important not only about parents and siblings, but also the medical history of children, nephews, grandparents, aunts and uncles. For those families in which the incidence of cancer is increased, it is recommended:

• Collect information about at least 3 generations of relatives;
• Carefully analyze information about the health of relatives on both the maternal and paternal side, since there are genetic syndromes that are inherited both through the female and male lines;
• Indicate information about male and female ethnicity in the pedigree, as some genetic changes are more common among representatives of certain ethnic groups;
• Write down information about any medical problems for each relative, since even those conditions that seem minor and unrelated to the underlying disease can serve as a clue to information about hereditary disease and individual risk;
• For each relative who has been diagnosed with a malignant neoplasm, it is necessary to indicate:
  • date of birth;
  • date and cause of death;
  • type and location of the tumor (if medical documents are available, it is highly advisable to attach a copy of the histological report);
  • age at which cancer was diagnosed;
  • exposure to carcinogens (for example: smoking, occupational or other hazards that can cause cancer);
  • methods by which the diagnosis was established and methods of treatment;
  • history of other medical problems;

Review your family medical history

Once all available family health information has been collected, it should be discussed with your personal physician. Based on this information, he will be able to draw conclusions about the presence of risk factors for certain diseases, draw up an individual plan for health checks, taking into account the risk factors inherent in a particular patient, and give recommendations on the necessary changes in lifestyle and habits that will be aimed at preventing the development of the disease.

It is also necessary to discuss the history of family diseases with your children and other relatives, as this can be useful for them in the sense of understanding responsibility for their health and developing a lifestyle that can prevent the development of the disease.

Genetic testing

In addition to identifying behavioral and occupational risk factors, analysis of family medical history may indicate the need for genetic testing, which examines genetic markers that indicate an increased risk of a particular disease, identifies carriers of the disease, makes a direct diagnosis, or determines the likely course of the disease.

In general terms, the signs that make one suspect a familial carriage of congenital cancer predisposition syndrome are the following:

• Repeated cases of cancer in close relatives, especially in several generations. The same type of tumor occurring in relatives;
• The onset of the tumor at an unusually young age (under 50 years of age);
• Cases of repeated malignant tumors in the same patient;

A family medical history containing any of these features may indicate an increased risk of cancer in family members. This information should be discussed with your doctor, and based on his advice, decide on further tactics to reduce your individual risk of the disease.

PROS and CONS of genetic testing

If you and your family members had an increased risk of developing cancer, would you want to know about it? Would you tell other family members? Genetic testing has now made it possible in certain cases to identify those potential patients who are at risk of developing cancer, but the decision to undergo these tests must be based on an understanding of the problem. Test results can upset a person’s mental balance and cause negative emotions towards their own health and the health of their family. Before deciding to undergo genetic testing, consult with your doctor, a geneticist and your loved ones. You must be sure that you are ready to correctly perceive this information.

Genes, their mutations and genetic tests

Genes contain certain information that is passed on from parents to children. Various variants of genes, as well as changes in their structure, are usually called mutations. If such a mutated form of the gene was received by a child from his parents, then we are talking about a congenital mutation. No more than 10% of all cancers are the result of congenital mutations. Only in rare cases can a single mutation cause cancer. However, some specific mutations can increase a carrier’s risk of developing cancer. Genetic tests can measure an individual’s risk of disease. Today there is no test that is 100% predictive of developing cancer, but tests can identify an individual’s risk if it is higher than the population average.

PROS of genetic testing

People decide to undergo genetic testing for cancer risk for a variety of reasons, depending on their specific situation. Some people want to understand the possible cause of an already developed disease, others want to understand the risk of developing cancer in the future or determine whether they are a carrier of the disease. Being a carrier of a disease means that a person has in his genome (“carries”) the gene for a certain disease, but there are no signs of developing the disease itself associated with this gene. Because carriers can pass the defective gene on to their children, genetic testing can be useful in determining the risk to planned offspring.

The decision to undergo testing is an individual one and should be made in consultation with your family and your doctor.

Reasons for undergoing genetic testing may include the following:

• The test result may be the basis for timely medical intervention. In some cases, individuals with a genetic predisposition may be able to reduce their risk of developing the disease. For example, women who carry the breast and ovarian cancer susceptibility gene (BRCA1 or BRCA2) are recommended to undergo preventive surgery. Also, people with an increased risk of developing cancer are advised to undergo more frequent diagnostic testing, avoid specific risk factors, or take preventive medications .
• Genetic testing can reduce anxiety. If someone has several relatives with cancer, which may indicate a genetic predisposition to cancer in the family, the result of genetic testing may help alleviate concerns.
• Questions to ask yourself before taking the tests: Before you decide to undergo genetic testing, you must be absolutely sure that you understand all the risks associated with obtaining the results of these tests and have sufficient grounds to undergo this research. It’s also helpful to think about what you will do with the results. Below are a few factors to help you make your decision:
  • Do I have a family history of cancer or family members who developed cancer at a relatively young age?
  • What will be my perception of the test results? Who can help me use this information?
  • Will knowing the test result change my or my family’s medical care?
  • If a genetic predisposition is discovered, what steps am I willing to take to minimize my personal risk?
• Additional factors influencing decision making:
  • Genetic tests have certain limitations and psychological implications;
  • Test results may cause depression, anxiety or guilt.

If someone receives a positive test result, it can cause anxiety or depression about the possibility of developing cancer. Some people begin to consider themselves sick, even if they never develop a tumor. If someone is not a carrier of a mutant variant of the gene, while other family members are, this fact can cause him to feel guilty (so-called “survivor’s guilt”).

• Testing can cause tension between family members. In some situations, an individual may feel responsible for the fact that members of his family turned out to be carriers of unfavorable heredity. which became clear thanks to his initiative to conduct testing. This can cause the development of tense relationships in the family.
• Testing can provide a false sense of security.

If a person’s genetic testing results are negative, this does not mean that person is completely protected from developing cancer. This only means that his personal risk does not exceed the average risk of developing cancer in the population.

• Test results may be unclear to interpret. The genotype of a particular individual may carry unique mutations that have not yet been tested for predisposition to the development of cancer. Or, a particular set of genes may contain a mutation that cannot be detected by available tests. In any case, this makes it impossible to determine the risk of developing cancer, and this situation can give rise to feelings of anxiety and uncertainty.
• Test results may raise personal privacy issues. The findings stored in the patient’s personal medical record may be disclosed to the employer or insurance company. Some people fear that genetic test results could lead to genetic discrimination.
• Currently, conducting genetic tests and interpreting their results is expensive and is not paid for by compulsory medical insurance or voluntary health insurance funds.

genetic counseling

It is a detailed informational conversation, during which a geneticist with advanced training in cancer genetics helps the patient or family members understand the meaning of medical information, talks about available methods of early diagnosis, optimal protocols for monitoring the health of family members, necessary prevention programs and treatment methods in case of disease development.

Typically the conversation plan includes:

• Identify and discuss existing risk. A detailed explanation of the significance of the detected genetic predisposition. Informing about available research methods and helping families make their own choices;
• Discussion of existing methods of diagnosis and treatment in case of tumor development. Review of available methods for early tumor detection or preventive treatment;
• Discussion of the benefits of testing and the risks it poses. A detailed explanation of the limitations of the genetic testing method, the accuracy of the test results, and the consequences that may result from receiving the test results;
• Signing the informed consent. Repetition of information about the possibilities of diagnosing and treating a probable disease. Clarifying the patient’s degree of understanding of the information discussed;
• Discussing with patients issues of confidentiality of genetic research;
• An explanation of the possible psychological and emotional consequences of taking the test. Helping the patient and family overcome the emotional, psychological, medical and social difficulties that may result from knowledge of a predisposition to developing a malignant disease.

What questions should you ask your cancer geneticist?

A conversation with a cancer geneticist includes gathering information about diseases that run in your family. Based on this conversation, conclusions will be drawn about your individual risk of developing cancer and the need for special genetic tests and cancer screening. When planning a visit with a genetic counselor, it is important to gather as much information as possible about your family’s medical history so that you can get the most out of your conversation.

What data might be useful?

• Firstly, your medical records, extracts, results of instrumental examination methods. tests and histological reports, if a biopsy or surgery was ever performed;
• A list of your family members indicating age, illness, and for the deceased – dates and causes of death. The list should include parents, siblings, children, aunts and uncles, nephews, grandparents, and cousins;
• Information related to the types of tumors that have occurred in your family and the age of family members when they got cancer. If histological reports are available. They will be very helpful.

What questions should be discussed during the consultation?

• Your personal medical history and screening plan;
• Family incidence of tumors. Usually a family tree is drawn up, including at least 3 generations, which indicates who developed the disease and at what age;
• The likelihood of a hereditary cancer syndrome in your family;
• Reliability and limitations of genetic testing in your case;
• Choosing the most informative strategy for genetic testing.

After the consultation, you will receive a written conclusion regarding your case; it is advisable to give a copy of this conclusion to the attending physician. If, as a result of the consultation, the need for genetic testing becomes obvious, then after receiving the results, a second visit to a genetic specialist will be required.

Genetic testing

Genetic testing is an analysis of DNA, RNA, human chromosomes and some proteins, which allows one to predict the risk of developing a particular disease, identify carriers of altered genes, accurately diagnose a disease or predict its prognosis in advance. Modern genetics knows more than 700 tests for a wide variety of diseases, including breast cancer, ovarian cancer, colon cancer and other rarer types of tumors. Every year more and more genetic tests are introduced into clinical practice.

Genetic tests aimed at identifying the risk of developing cancer are “predictive” tests, which means that the test results can help determine the likelihood of a particular tumor developing in a particular patient during his or her lifetime. However, not every carrier of a tumor-associated gene will develop a malignant disease during their lifetime. For example, women who carry a certain mutation have a 25% risk of developing breast cancer, while 75% of them will remain healthy.

An oncologist in Moscow recommends genetic testing only for those patients who have a high risk of carrying a congenital genetic mutation that determines the risk of developing a malignant tumor.

The following are factors that will help identify patients at risk:

• Having a family history of cancer;
• three or more relatives on the same line have the same or related forms of cancer;
• Early development of the disease. Two or more relatives were diagnosed with the disease at a relatively early age;
• Multiple tumors. Two or more tumors developing in the same family member.

Many genetic tests are being developed to identify those mutations that increase the risk of developing cancer, but methods to prevent tumor development are not always available; in many cases, genetic testing can only diagnose a tumor as early as possible. Therefore, before deciding to conduct genetic research, the patient must be fully aware of the psychological burden that knowledge of an increased cancer risk can bring. The examination procedure begins with the signing of “informed consent for genetic testing,” which explains the essence and specifics of the planned