With the development of oncology, scientists have learned to find weak points in tumors - mutations in the genome of tumor cells.

A gene is a piece of DNA that has been inherited from parents. A child receives half of its genetic information from its mother and half from its father. There are more than 20,000 genes in the human body, each of which performs its own specific and important role. Changes in genes dramatically disrupt the flow of important processes inside the cell, the functioning of receptors, and the production of necessary proteins. These changes are called mutations.

What does gene mutation mean in cancer? These are changes in the genome or in tumor cell receptors. These mutations help the tumor cell survive in difficult conditions, multiply faster and avoid death. But there are mechanisms by which mutations can be disrupted or blocked, thereby causing the death of the cancer cell. In order to target a specific mutation, scientists have created a new type of anticancer therapy called Targeted Therapy.

The drugs used in this treatment are called targeted drugs. target - target. They block gene mutations in cancer, thereby starting the process of destroying the cancer cell. Each cancer location is characterized by its own mutations, and for each type of mutation only a specific targeted drug is suitable.

That is why modern cancer treatment is based on the principle of deep tumor typing. This means that before starting treatment, molecular genetic research tumor tissue, allowing to determine the presence of mutations and select individual therapy which will give the maximum antitumor effect.

In this section we will tell you what there are gene mutations in cancer, why it is necessary to do a molecular genetic study, and what drugs affect certain gene mutations in cancer.

First of all, mutations are divided into natural And artificial. Natural mutations occur involuntarily, while artificial ones occur when the body is exposed to various mutagenic risk factors.

There is also classification of mutations based on the presence of changes in genes, chromosomes or the entire genome. Accordingly, mutations are divided into:

1. Genomic mutations- These are cell mutations, as a result of which the number of chromosomes changes, which leads to changes in the cell’s genome.

2. Chromosomal mutations - These are mutations in which the structure of individual chromosomes is rearranged, resulting in the loss or doubling of part of the genetic material of the chromosome in the cell.

3. Gene mutations- these are mutations in which there is a change in one or more various parts gene in a cell.

Scientists today know that the growth process cancerous tumor begins when one or more genes in a cell undergo a process of mutation. This means that the gene either begins to code for a changed, abnormal protein, or changes so much that it no longer codes for the protein at all. As a result, the normal processes of cell growth and division are disrupted, which can lead to the formation of a malignant tumor.

Genetic mutations can occur during different time periods human life: if they occur before a person is born, then all cells in the body will contain this mutated gene (germ mutation), and it will be inherited, or the mutation can occur in a single cell of the body during life, and the changed gene will be contained only in the cells -descendants of the single cell in which the mutation occurred (somatic mutations). Most malignant diseases develop as a consequence of a random mutation in a single cell, the further division of which produces tumor progeny. However, about 10% of cases malignant neoplasms It is hereditary in nature, that is, a mutation that predisposes to cancer is passed on from generation to generation.

What is the probability that the altered gene will be inherited?

Any cell in the body contains two copies of the same gene, one of these copies is inherited from the mother, the other from the father. When a mutation is passed from parents to child, it is present in every cell of the child’s body, including the cells reproductive system- sperm or eggs, and can be transmitted from generation to generation. Germ mutations are responsible for the development of less than 15% malignant tumors. Such cases of cancer are called "familial" (that is, passed on in families) forms of cancer. However, inheriting one copy of the altered gene does not mean that the tendency to develop a certain type of tumor is also inherited. The fact is that hereditary diseases can have different type inheritance: dominant, when one inherited copy of the gene is sufficient for the development of the disease, and recessive, when the disease develops if the altered gene is received from both parents. In this case, parents who have only one altered gene in their hereditary apparatus are carriers and do not themselves get sick.

Genetics of breast cancer

Most cases of breast cancer (BC) - about 85% - are sporadic, that is, damage to genes occurs after a person is born. Congenital forms of breast cancer (about 15%) develop when a mutant form of the gene is inherited by the patient, passed on from generation to generation. There are several types of genes that are involved in the development of breast cancer, including mutations that cause loss of tumor suppressor genes.

In accordance with their name, “tumor suppressor genes” prevent the occurrence of tumor processes. When their activity is disrupted, the tumor is able to grow uncontrolled.

Normally, each cell in the body carries two copies of each gene, one from the father and one from the mother. Breast cancer is usually inherited in an autosomal dominant manner. With an autosomal dominant mode of inheritance, it is sufficient for the mutation to occur in only one copy of the gene. This means that the parent who carries a mutant copy of the gene in its genome can pass on both it and a normal copy to its offspring. Thus, the probability of transmitting the disease to a child is 50%. Presence in the genome cancer mutation increases the risk of developing tumors that are specific to this mutation.

What is the average risk of developing breast cancer?

The average woman has a lifetime risk of developing breast cancer of about 12%. According to other data, every 8th woman will develop breast cancer during her lifetime.

How common is breast cancer?

Breast cancer is the most common tumor in women (excluding skin cancer, which is very common in the elderly and old age) and the second most common cause deaths from tumors after lung cancer. Breast cancer also occurs in men, but its frequency is approximately 100 times lower than in women.

In order to identify individuals at risk for developing breast cancer, it is recommended to conduct genetic testing among patients with a family history of breast cancer. Most experts insist on conducting a preliminary consultation with a geneticist before deciding to undergo genetic testing. The specialist must discuss with the patient all the pros and cons of genetic testing, so it is necessary to make an appointment with a geneticist.

What should a woman know about the likelihood of breast cancer transmission in her family?

If close relatives (mother, daughters, sisters) have breast cancer, or if other family members (grandmothers, aunts, nieces) have had this disease several times, this may indicate the hereditary nature of the disease. This is especially likely if the diagnosis of breast cancer was made to one of the relatives who has not reached the age of 50 years.

If first-degree relatives (mother, sister or daughter) develop breast cancer, then the risk of developing the disease increases by 2 times compared to the average. If two of your close relatives become ill, then the risk of developing breast cancer during your lifetime is 5 times higher than the statistical average. At the same time, it is unclear how many times the risk of getting the disease increases for a woman whose family has had a male relative with breast cancer.

What hereditary mutations increase the risk of developing breast cancer?

There are several genes associated with an increased risk of breast cancer. The most common syndromes associated with an increased risk of developing breast cancer are described below.

• The BRCA1 and BRCA2 genes (BRCA = BReast CAncer) are tumor suppressor genes that are damaged in familial breast cancer syndrome. Those women who are carriers of a mutant form of the BRCA gene have a 50-85% chance of developing breast cancer during their lifetime. However, their risk of developing ovarian cancer is about 40%. Men who carry mutant forms of the BRCA1 or BRCA2 genes in their genome may also have an increased risk of developing breast or prostate cancer. Both men and women who have a BRCA2 gene mutation may belong to the group increased risk development of breast cancer or other types of cancer. The mutant form of the gene has a certain accumulation in some ethnic groups, for example, approximately one in 50 Ashkenazi Jewish women carries a congenital mutation in the BRCA1 or BRCA2 gene, which increases the risk of developing breast cancer during life to 85% and the risk of developing ovarian cancer to 40 %. It is currently known that about 80% of all hereditary breast cancer are caused by mutant forms of the BRCA1 and BRCA2 genes.
• Ataxia-telangiectasia (A-T). A hereditary syndrome called ataxia-telangiectasia is caused by a mutation in a gene located on chromosome 11, the so-called ATM gene. With this syndrome, the risk of developing breast cancer also increases.
• Lee-Fromeny syndrome. Members of families with Leigh Fromen syndrome (LFS) have a 90% chance of developing cancer during their lifetime. The most common tumors that develop in SLF are: osteogenic sarcoma, soft tissue sarcoma, leukemia, lung cancer, breast cancer, brain tumors and adrenal cortex tumors. This rather rare syndrome accounts for less than 1% of all breast cancers. The gene with which SLF is associated is called "p53". This gene is a tumor suppressor gene. Testing for the presence of the p53 gene is recommended for family members who meet diagnostic criteria for FFS. Many studies are being conducted to achieve a better understanding of the mechanism of development of LFS. Another gene that has been studied, CHEK2, may lead to the development of a syndrome resembling FFS in some families. In carriers of a mutant form of this gene, the risk of developing breast cancer is increased by 2-5 times among women and 10 times among men. Testing for mutations in the CHEK2 gene region is currently available as part of research.
• Cowden's syndrome. Women with Cowden syndrome have an increased risk of developing breast cancer during their lifetime, which ranges from 25% to 50%, and a 65% risk benign neoplasms mammary glands. Also with this disease there is an increased risk of developing uterine cancer, which ranges from 5% to 10% and much more - the likelihood of developing benign processes in the uterus. Cowden syndrome increases the likelihood of developing cancer and benign tumors thyroid gland. Other signs of Cowden syndrome include macrocephaly - a large head size - and skin changes such as trichilemmomas and papillomatous papulosis. The gene associated with Cowden's syndrome is called. PTEN. It is also believed to be a tumor suppressor gene, and specific tests have been developed to identify it.
• In women with PCY, the lifetime risk of developing breast cancer is increased to 50%. However, the main symptom of SPY is the presence of multiple hamartomatous polyps in the digestive tract. The presence of these polyps significantly increases the risk of developing colon and rectal cancer. People with PI syndrome also have increased pigmentation (dark spots on the skin) of the face and hands. Hyperpigmentation often begins in childhood and lasts throughout life. This syndrome also implies an increased risk of developing cancer of the ovaries, uterine body and lungs. The gene associated with SPY is called STK11. The STK11 gene is a tumor suppressor gene and can be identified through genetic testing.
• Other genes. Currently, much remains unknown regarding the role of individual genes in increasing the risk of developing breast cancer. It is possible that there are other genes, not yet identified, that influence the hereditary predisposition to the development of breast cancer.

In addition to family history, there are additional environmental and lifestyle risk factors that may also increase the risk of developing breast cancer. To better understand your own risk of developing cancer, you should discuss your family medical history and personal risk factors with your doctor. Those people who have an increased risk of developing breast cancer can undergo special genetic testing and follow their individual plan early diagnosis. In addition, they need to rule out those additional risk factors that can be excluded. Regarding the risk of developing breast cancer, such controllable risk factors are: unbalanced diet, overweight, physical inactivity, alcohol abuse, smoking and uncontrolled use of female sex hormones.

Genetics of ovarian cancer

For any woman without a family history of increased incidence of ovarian cancer and no other risk factors, the lifetime risk of developing ovarian cancer is less than 2%.

Ovarian cancer accounts for about 3% of all malignant tumors that develop in women.

It ranks 8th among all oncological women's diseases and the 5th leading cause of death for women from cancer, which an oncologist can confirm to you.

How do you know if a hereditary form of ovarian cancer runs in your family?

If close relatives (mother, sisters, daughters) have had cases of ovarian cancer, or several cases of the disease occurred in one family (grandmother, aunt, niece, granddaughters), then it is possible that in this family ovarian cancer is hereditary. .

If a first-degree relative has been diagnosed with ovarian cancer, then the individual risk of a woman from this family is on average 3 times higher than the average statistical risk of developing ovarian cancer. The risk increases even more if the tumor has been diagnosed in several close relatives.

What hereditary genetic mutations increase the risk of developing ovarian cancer?

To date, scientists know several genes, mutations in which lead to an increased risk of developing ovarian cancer.

The most common inherited syndromes associated with the risk of developing ovarian cancer are described below.

• Hereditary breast-ovarian cancer (HBOC) syndrome. Damage to the BRCA1 and BRCA2 genes is the most common situation in cases of familial cancer mammary gland and ovaries. It was calculated that mutations in the BRCA1 gene occur in 75% of cases of hereditary forms of ovarian cancer, and the BRCA2 gene is responsible for the remaining 15%. At the same time, the risk of ovarian cancer ranges from 15% to 40% throughout life, and breast cancer - up to 85%. Men who carry mutant forms of the BRCA1 or BRCA2 genes in their genome may also have an increased risk of developing breast or prostate cancer. Carrying mutations in the BRCA2 gene is also associated with an increased risk of developing other types of cancer: melanoma and pancreatic cancer. The BRCA1 and BRCA2 genes belong to the so-called “tumor suppressor genes.” This means that based on these genes, a protein involved in cell cycle and limiting the number of cell divisions. This limits the likelihood of tumor formation. If a mutation occurs in tumor suppressor genes, the protein is either not synthesized at all or has a defective structure and is not able to prevent the formation of tumor cells.
  The mutant form of the gene has a certain accumulation in some ethnic groups: there are three most common mutations: 2 in the BRCA1 gene and one in the BRCA2 gene, in the Ashkenazi Jewish population. Among this population, the risk of carrying one of the three forms of mutant genes is 2.5%.
  Women who carry mutations in the BRCA1 or BRCA2 genes should undergo careful screening for early detection of ovarian and breast cancer. Screening for early detection ovarian cancer should include: examination by a gynecologist, ultrasound examination of the pelvic organs and a blood test for the CA-125 oncogene. Screening for early detection of breast cancer should include: breast self-examination, examination by a mammologist, mammography once a year, ultrasonography mammary glands and MRI.
• Hereditary Nonpolyposis Colon Cancer (HNPTC) (Lynch syndrome) accounts for about 7% of the incidence of hereditary ovarian cancer. Women with this syndrome have a 10% risk of developing ovarian cancer. The risk of developing uterine cancer is up to 50%. NNPTC is most often associated with a risk of developing colon cancer, which ranges from 70 to 90%, many times higher than the risk in the general population. Patients with NNPTC also have an increased risk of developing stomach cancer. small intestine and kidneys. There is also an increased incidence of breast cancer in these families.
  Scientists have found several genes, breakdowns in which lead to the development of NPTK. Most common cause syndrome are mutations in the MLH1, MSH2 and MSH6 genes. Although mutations are most often found in several genes at once, families have been described in which changes are found in only one gene.
  The genes in which mutations cause the development of NPTK syndrome are representatives of a group of genes belonging to the so-called mismatch repair genes. The genes of this group synthesize proteins that restore errors in the DNA structure that occur during cell division. If one of these genes is modified, a protein is formed that is unable to eliminate errors in the DNA structure; the defective DNA structure increases from one cell division to another, which can lead to the development of cancer.
  Women from families in which NPTCC is diagnosed should undergo mandatory additional screening for the early detection of uterine and ovarian cancer, in addition to tests aimed at the early detection of colon cancer.
• Peutz-Jeghers syndrome (SPJ). Women with PCY have an increased risk of developing ovarian cancer. Although the main symptom of SPY is the presence of multiple hamartomatous polyps in the digestive tract. The presence of these polyps significantly increases the risk of developing colon and rectal cancer. People with PI syndrome also have increased pigmentation (dark spots on the skin) of the face and hands. Hyperpigmentation often appears in childhood and may fade over time. In women from families with PCY, the risk of developing ovarian cancer is about 20%. This syndrome also implies an increased risk of developing cancers of the uterus, breast and lungs. The gene associated with SPY is called STK11. The STK11 gene is a tumor suppressor gene and can be identified through genetic testing.
• Nevusoid cell carcinoma syndrome (NBCC) Also known as Gorlin syndrome, it is characterized by the development of multiple basal cell carcinomas, cysts of the jaw bones, and small pockmarks on the skin of the palms and soles of the feet. In women with Gorlin syndrome, benign ovarian fibroids develop in 20% of cases. There is a definite, although minor, risk that these fibromas may develop into malignant fibrosarcomas. An additional complication of the syndrome is the development of brain tumors - medulloblastomas in childhood. External features of patients with Gorlin syndrome include macrocephaly (large head size), unusual facial structure, and skeletal abnormalities affecting the structure of the ribs and spine. Despite the fact that SNBCC is inherited in an autosomal dominant manner, about 20-30% of patients do not have a family history of the disease. It is known that the PTCH gene is associated with the disease, the structure of which can be determined in special tests.

Are there other inherited conditions that lead to an increased risk of developing ovarian cancer?

Other congenital conditions that increase the risk of developing ovarian cancer include:

• Lee-Fromeny syndrome. Members of families with Leigh Fromen syndrome (LFS) have a 90% chance of developing cancer during their lifetime. The most common tumors that develop in SLF are: osteogenic sarcoma, soft tissue sarcoma, leukemia, lung cancer, breast cancer, brain tumors and adrenal cortex tumors. This syndrome is quite rare and is caused by a mutation in a gene called p53, which is a tumor suppressor gene. Testing for the presence of the p53 gene is recommended for family members who meet diagnostic criteria for FFS. Many studies are being conducted to better understand the mechanism of development of LFS. Another known gene, CHEK2, can lead to the development of a syndrome resembling LFS in some families.
• Ataxia-telangiectasia (A-T) a rare inherited autosomal recessive disorder characterized by progressive gait disturbances that usually develop in childhood. Soon after acquiring walking skills, children begin to stumble, their gait becomes unsteady, and most patients with A-T are forced to use a wheelchair. Over time, speech impairments and difficulty writing and performing precise movements develop. When examining patients, they are noticeable on the skin, mucous membranes and sclera of the eyes. spider veins, called telangiectasia, which are dilated capillaries. Patients with this syndrome also have a weakened immune system and are susceptible to infectious diseases. The risk of developing tumors is 40%, of which malignant lymphomas are the most common. The risk of developing breast, ovarian, stomach and melanoma cancers also increases.
  A-T is inherited in an autosomal recessive manner, that is, for the development of the disease it is necessary to inherit 2 mutant copies of a gene called the ATM gene and located on chromosome 11. This means that both parents of an affected child must be carriers of the altered gene, and their children have a 25% chance of inheriting the disease. Carriers of the altered ATM gene have an increased risk of developing certain forms of malignant diseases. First of all, breast cancer.
• Complex KARNEY is a rare inherited condition characterized by patchy skin pigmentation, most commonly affecting the face and lips, that appears during puberty. In addition to skin spots, patients with this syndrome are prone to developing numerous benign tumors, the most common of which are myxomas, which are skin nodules of varying colors from white to bright pink, located on the eyelids, auricle and nipples. About 75% of patients with CARNEY complex develop thyroid tumors, but most of them are benign. At all. The risk of developing malignant tumors in patients with CC is considered to be low. CARNEY complex is a congenital condition with an autosomal dominant pattern of inheritance. Despite this, approximately 30% of patients have no family history of the disease. One of the genes responsible for the development of this condition is called PRKAR1A. A second gene, thought to be located on chromosome 2, is under investigation and scientists believe it may also be associated with the development of the disease.

What determines your personal risk level?

In addition to a strong family history, there are additional risk factors associated with behavioral habits and the environment. These factors may influence your risk of developing ovarian cancer. Women at increased risk of developing the disease can undergo genetic testing to determine the need for screening tests aimed at early diagnosis of ovarian cancer. In particularly dangerous situations, a prophylactic orophorectomy (removal of healthy ovaries to reduce the risk of breast and ovarian cancer) may be recommended.

Carrying certain genetic mutations that increase the risk of developing ovarian cancer does not mean a 100% chance of developing this type of tumor. In addition, controllable risk factors play a significant role, including such well-known ones as excess weight, smoking, alcohol consumption and a sedentary lifestyle.

The role of genetic factors in the development of kidney cancer

Kidney cancer most often develops as a random event, that is, about 95% of cases do not have hereditary causes that would be known to today's science. Only 5% of kidney cancers develop due to a hereditary predisposition. Thus, the average risk of developing kidney cancer is less than 1% throughout a person’s lifetime, and men are affected twice as often as women.

How can you tell if there is a family history of developing kidney cancer?

If immediate family members (parents, siblings, or children) have developed a kidney tumor, or have had multiple cases of kidney cancer among all family members (including grandparents, uncles, aunts, nephews, cousins, and grandchildren) , that is, there is a possibility that this is a hereditary form of the disease. This is especially likely if the tumor developed before age 50, or if there is bilateral disease and/or multiple tumors in one kidney.

What is the individual risk of developing kidney cancer if there is a family history?

If first-degree relatives (parents, siblings, children) had kidney cancer before the age of 50, this means that the risk of developing the disease may be increased. To determine an individual's risk level, it is necessary to identify the inherited condition that may have led to the development of cancer.

Which congenital genetic mutations increase the risk of kidney cancer?

There are several genes that are known to be associated with the development of kidney cancer, and new genes affecting this process are being described every year. Some of the most common genetic conditions that increase your risk of developing kidney cancer are outlined below. Most of these conditions lead to the development of some type of tumor. Understanding the specific genetic syndrome in a family can help the patient and his or her physician develop an individual plan for prevention and early diagnosis and, in certain cases, determine the optimal treatment tactics. Some of the hereditary conditions are also associated, in addition to the risk of developing tumors, with an increased likelihood of developing certain non-tumor diseases, and this knowledge can also be useful.

• Von Hippel-Lindau syndrome (VHL). People with hereditary FHL syndrome are at risk for developing several types of tumors. Most of these tumors are benign (noncancerous), but in about 40% of cases there is a risk of developing kidney cancer. Moreover, a certain specific type, called “clear cell kidney cancer”. Other organs. Tumors susceptible to the development in patients with FHL syndrome are the eyes (retinal angiomas), the brain and spinal cord (hemangioblastomas), the adrenal glands (pheochromocytoma) and inner ear(tumors of the endolymphatic sac). The development of a tumor of the hearing organ can cause complete or partial hearing loss. Patients with FHL may also develop cysts in the kidneys or pancreas. The syndrome manifests itself clinically at the age of 20-30 years, but symptoms may also appear in childhood. About 20% of patients with FHL syndrome have no family history of the disease. The gene that determines the development of FHL syndrome is also called the VHL gene (VHL) and belongs to the group of tumor suppressor genes. Tumor suppressor genes are usually responsible for the synthesis of a specific protein that limits cell growth and prevents the emergence of tumor cells. Mutations in suppressor genes cause the body to lose its ability to limit cell growth and, as a result, tumors can develop. Genetic testing to determine mutations in the FHL gene, it is recommended for persons with a family history of diseases associated with FHL syndrome. Screening for symptoms of FHL syndrome should be carried out in families whose members are at increased risk of developing this syndrome, and begin at early age. This screening includes:
  • Eye examination and blood pressure monitoring from age 5 years;
  • Ultrasound of organs abdominal cavity from early childhood, MRI or CT of the retroperitoneal organs after 10 years;
  • Test for the level of catecholamines in 24-hour urine;
• Familial cases of clear cell renal cell carcinoma not associated with FHL syndrome. Most cases of clear cell kidney cancer are sporadic, meaning they develop at random. However, there is a very low percentage of familial cases of clear cell renal cell carcinoma in the absence of other features of FHL syndrome. Some of these patients inherit specific gene rearrangements on chromosome 3. Genetic diagnostic techniques can identify such rearranged chromosomes. In some patients genetic reasons The development of kidney cancer is not yet known. For family members with such rare syndromes It is recommended to begin examination to detect kidney tumors at the age of 20 years using ultrasound, MRI or CT of the retroperitoneal organs.
• Congenital papillary renal cell carcinoma (CPRCC). PPCC may be suspected when two or more close relatives are diagnosed with the same type of kidney tumor, namely papillary renal cell carcinoma type 1. Typically, this type of tumor in familial cases is diagnosed at the age of 40 years or later. Patients with SPPCC may have multiple tumors in one or both kidneys. Individuals belonging to families with inherited cases of PPCC should undergo screening diagnostic studies, including ultrasound, MRI or CT, from the age of about 30 years. The gene responsible for the development of VPPCC is called c-MET. The c-MET gene is a proto-oncogene. Proto-oncogenes are responsible for the synthesis of proteins that trigger cell growth in a normal cell. Mutations in proto-oncogenes cause too much of this protein to be produced and the cell receives too much of a signal to grow and divide, which can lead to tumor formation. Currently already developed special methods, allowing to identify mutations in the c-MET gene.
• Burt-Hogg-Dubet syndrome (BHD). HDD syndrome is a rare syndrome and is associated with the development of fibrofollicles (benign tumors of the hair follicle), cysts in the lungs and an increased risk of kidney cancer. In patients with HDD syndrome, the risk of developing kidney cancer is 15-30%. Most kidney tumors that develop in this syndrome are classified as chromophobe tumors or oncocytomas, but in rare cases clear cell or papillary kidney cancer may develop. Due to the increased risk of developing malignant kidney tumors, members of families with HDD syndrome are advised to start early regular diagnostic tests to exclude this pathology (ultrasound, MRI or CT from the age of 25 years). The gene responsible for the development of HDD syndrome is called BHD, and can be determined through genetic testing.
• Congenital leiomyomatosis and renal cell carcinoma (CCRCC). Patients with this syndrome have skin nodules called leiomyomas. Most often, such nodes form on the limbs, chest and back. Women are often diagnosed with uterine fibroids, or, much less commonly, leiomyosarcoma. Patients with VLPPC have an increased risk of developing kidney cancer, which is about 20%. The most common type is papillary renal cell carcinoma. Screening for early detection of kidney cancer should be carried out among family members with VLPKD. The gene responsible for the development of this syndrome is called the FH gene (fumarette hydratase) and can be determined through genetic testing.

Are there other congenital conditions associated with increased level development of kidney cancer?

Clinical observations show that there are other cases of familial predisposition to the development of kidney tumors, and this topic is receiving increased attention from geneticists. A less significant increase in the risk of developing kidney cancer is observed in patients with tuberous sclerosis, Cowden's syndrome, and congenital nonpolyposis colon cancer. For all these diseases, consultation with a geneticist is indicated.

Genetics of prostate cancer

Most cases of prostate cancer (about 75%) occur as a result of somatic mutations and are not transmitted randomly or hereditarily. Hereditary cancer prostate gland SOS

Main causes of cancer: random mutation DNA, environment and heredity

Panel "Khrushchev" buildings and houses lined with granite can pose a threat to people and cause cancer. Residents of the southeastern regions of Tatarstan are unlucky, because their soil contains an prohibitive concentration of the metal. Based on these and other examples, oncologist of the Republican Clinical Oncology Dispensary, professor of the department of oncology, radiology and palliative medicine KSMA and Doctor of Medical Sciences Ilgiz Gataullin reveals the main factors in cancer

Panel "Khrushchev" buildings and houses lined with granite can pose a threat to people and cause cancer. Residents of the southeastern regions of Tatarstan are unlucky, because their soil contains an prohibitive concentration of the metal. Based on these and other examples, oncologist of the Republican Clinical Oncology Dispensary, professor of the Department of Oncology, Radiology and Palliative Medicine of KSMA and Doctor of Medical Sciences Ilgiz Gataullin reveals the main factors in developing cancer.

Ilnur Yarkhamov - Kazan

- How does a cancer cell form?

Cancer cells are the result of many mutations. Tumor transformation of a cell occurs when it accumulates a certain number of mutations (from 5 to 10), critical for carcinogenesis. Combinations of mutations can be very different, so from a molecular genetic point of view, no two tumors are identical. The uniqueness of tumors exceeds the uniqueness of fingerprint patterns. In other cases, these are congenital genetic defects that lead to the development of cancer. The probability of developing cancer in carriers of this inherited defect reaches 100%. These include some types of breast cancer, stomach cancer, colorectal cancer. Thus, the basis of cancer is cell mutation. In addition, the frequency of mutations is related to the number of cell divisions.

Therefore, cancer occurs more often in those organs whose cells divide more often. This is logical, because the more often cells divide, the more often mutations accumulate.

- What organs does a person have?

For example, human brain cells - neurons - practically do not divide. There, gliomas - brain tumors - occur very rarely. The process of cell division is most active in epithelial cells and hematopoietic organs (red Bone marrow). Therefore, leukemia, lymphogranulomatosis, tumors of the lungs and gastrointestinal tract are much more common.

- And the lifespan of a cell...

The older a person is, the higher a person's risk of developing cancer. Especially after 60 years. In general, there is an opinion that every person is doomed to get cancer. That is, the end of our life is cancer.

Another thing is that a person may not live to see his cancer due to cardiovascular, respiratory pathology or any injuries.

What causes the mutation itself? About 60% of mutations leading to cancer occur due to random errors in DNA replication (synthesis of a daughter DNA molecule on the template of a parent DNA molecule, - Ed. ) , 10% are due to heredity and 30% are caused by environmental factors, including ecology, etc. These include dietary habits, smoking, insolation, radiation, nutritional supplements, dioxins or benzopyrene ( aromatic compound, formed during the combustion of hydrocarbon liquid, solid and gaseous fuels - Ed.). Also possible hormonal disorders in humans. For example, hyperestrogenemia in women - an increase in estrogen levels leads to mutations in the cells of hormonal organs. These are the mammary gland, ovaries, thyroid and prostate glands, etc.

Stressful situations in a person’s life can also be considered risk factors for cancer. But here the action is a little different - against the background of stress, chronic pathology immunity and the body's defenses decrease. And since there is no natural immunity, the transformed cells are not destroyed and are the basis for tumor growth.

As you can see, there are many causes of cancer. But the basis of all is cell mutation.

- Who is most at risk for cancer?

In general, we all take risks. Especially residents of big cities. Because a huge share of pollution in the city comes from automobile traffic.

Village residents, by the way, are also not immune from anything. Although there is an opinion that they live closer to and around nature clean ecology. There is great amount pesticides and fertilizers that have been applied to the fields for years and decades. All this affects the villagers.

I operated on a patient a few weeks ago. Her family is from the Verkhneuslonsky district. It would seem like a clean place, on the other side of the Volga. In their large family, I have already operated on five people with cancer of various localizations. And two daughters-in-law - twice each, one for breast and stomach cancer. The other is about breast and colon cancer.

They do not have a genetic dependence, because oncology in everyone’s family is different. Therefore it cannot be said that villager insured against cancer.

- What about the industrial and chemical cities, Nizhnekamsk, Naberezhnye Chelny, Mendeleevsk?

There, it is not only the aging of city residents that contributes to the disease of the population. There are large factories and production facilities there. There was a huge fire at a KAMAZ truck in Chelny in 1993, after which the number of cancer patients in the city increased. There was a clear spike following the fire.

In Nizhnekamsk, the townspeople, of course, are also young. But now the trend is upward malignant tumors there is one of the highest in the republic, if not the highest. Statistics show growth rates, but in terms of the number of diseases they have not yet surpassed Kazan.

- What types of oncology are most often caused by environmental problems?

Ecology has many pollutants. But in general, carcinogens have two points of application. The first is the place of introduction into the body. The second is the place of release. In the first case we are talking about the lungs, gastrointestinal tract and skin. It is precisely through them that most cancers are diagnosed in our republic. And in the second case, we are talking, again, about the gastrointestinal tract, colon and urinary tract (kidneys, bladder). They also have a fairly high morbidity rate.

I watched a scientific and educational program on the Internet about the causes of cancer. I noticed this detail. It turns out that in St. Petersburg, a 15-30 minute walk on granite slabs can be equivalent to one X-ray.

Absolutely right. We also have something similar in Kazan. Granite contains small amounts of radioactive substances. Those, in turn, when they decay, release radon, an inert radioactive gas. It is slightly heavier than air. We once conducted research, but never published it. These studies were related to lung cancer... At one time, our Khrushchev panel buildings were built from granite chips. According to hygienists and a number of studies, higher concentrations of radon are detected in the basements of these houses than in the surrounding air. This also applies to buildings that are lined with granite slabs. When we made a correlation, it turned out that people living in these Khrushchev buildings on the first floors were more likely to develop lung cancer for many decades. Apparently due to exposure to radon.

- Maybe there was such a time that it was impossible to publish such things?

Not really. We studied soil pollution throughout Tatarstan. By the way, oil workers, employees of the Kazan Geolnerud Institute, in particular Professor Ozol Alfred Alfredovich, helped us a lot in this. When they were looking for deposits throughout almost all of Tatarstan, the soil and plants were examined for heavy metals.

In nature, we initially have a high concentration of metals in the soil due to some geological anomalies. And there is metal pollution, for example, near large industries, after applying fertilizers and pesticides to the soil.

As a result, spots appear on the map of Tatarstan - the areas most contaminated with metals. We have one of the most polluted areas - the southeast of the republic. What this is actually connected with is difficult to say. Maybe it's pollution, or maybe it was like that in the first place. But the fact is a high concentration of metals.

In the same areas of southeast Tatarstan, we analyzed cancer incidence for 10 years. A clear correlation was found with soil contamination with heavy metals. The most common cancers were skin, lung, and colon.

There are also a number of districts in the north of Tatarstan, this is the Mendeleevsky district, for example. The Zelenodolsk region, Kazan with its surroundings and the right bank of the Volga - Verkhne-Uslonsky and Kama-Ustinsky districts - are very polluted. Firstly, the “wind rose” in the direction from Kazan is also involved in this. Secondly, the Volga water itself is polluted, since the current carries all the pollutants to the right bank. And people drink river water and water their gardens with it. By the way, in the last two areas there is a very high incidence of cancer.

And the cleanest areas we have, in ecological terms, are Baltasinsky, Atninsky, and Arsky.

- Isn’t the sun to blame for skin cancer?

The sun is one of the risk factors for developing skin cancer and melanoma. Not every person, but many today can afford to travel somewhere to Turkey. Sunbathing for a week is already a powerful blow to the skin. Girls who think that chocolate skin color is beautiful are unhappy. They sunbathe in solariums, naturally this is also a risk factor. After some time, this may manifest itself as some kind of skin pathology. In addition, dust and soot also affect the skin.

- In what case does immunity not protect us? Can you describe the mechanism of how immunity works in the case of oncology?

Immunity provides us with a barrier to infection and cancer. Firstly, the cell itself has a defense mechanism. There are genes that cause cell suicide. As soon as a cell’s genotype changes, a mutation occurs, biochemical processes are disrupted, this gene is immediately activated and the pathological cell self-destructs.

But at some stage, a mutation occurs in this particular gene, which is designed to destroy cells. As a result, pathological cells begin to divide.

Secondly, there is immune defense. It also destroys these malignant cells. But at some stage, usually with age, under the influence of toxic substances, radiation, stressful situation, severe illness, the body's defenses are reduced. Malignant cells begin to actively multiply.

Stress itself, in small doses, is beneficial. It stimulates the immune system. But when it is chronic, constant stress over months or years, it reduces immunity.

I simulate the situation: a person does not smoke, does not drink, eats healthy food, but lives next to some factory; a busy highway runs past his house. Also, this man lives in a Khrushchev panel building, on the first floor. Is it enough for him? healthy image life so as not to get cancer?

That's a very difficult question. Because, despite the correct way of life of a person, external factors will still influence him. Sooner or later some changes in his body will occur.

Every person has mutated cells in their body. They are constantly being produced. Another thing is that they do not develop, do not circulate, or are suppressed. But when the body's defenses sharply decrease, cancer cells begin to reproduce.

Which modern theories Is there anything about the causes of cancer in the scientific and medical community that would reveal the environmental factor?

- We are now continuing to study the effect of metals on the human body. Research is currently being carried out jointly with radiobiologists, in particular with Corresponding Member of the Academy of Sciences of the Republic of Tatarstan Robert Ilyazov. Several areas in Tatarstan were examined where there is a high concentration of metals in soil and water.

Scientists have traced the chain of metals in herbs, in cow's milk, and in women's blood and milk. It was discovered that a child already receives a large dose of metals during breastfeeding. What will happen to him in 30-40 years is a very difficult question.

There are plants that accumulate heavy metals (lead, chromium, cadmium, uranium, etc.) in large quantities in above-ground organs, for example, creeping clover, annual sunflower, sedge. At one time, we proposed introducing this method of reclamation of agricultural land in a number of regions of Tatarstan. This applies to the area where there is a high concentration of heavy metals. You can sow fields with these grasses for 2-3 years. Then these grasses are mowed and disposed of.

- Let's return to the genetic factor.

Genes responsible for the occurrence of cancer of the mammary glands, ovaries, colon, and stomach can be transmitted from both the mother and the father. If the gene is inherited, then the risk of developing cancer depends on the specificity of the gene, its manifestation in the family history, and also on individual characteristics body.

I know one family in which, for three generations, all women in the family died of breast cancer. My grandmother died of breast cancer at the age of 40, and she was very aggressive form with metastases. My mother also died at the age of 40-42 from breast cancer with metastases. Three daughters also died from this disease in the same 40-42 years.

I watched my younger sister for several years. I examined her every six months. She had an ultrasound and mammogram. And at the age of 38, they found a small lesion in the mammary gland. We decided to excise it to prevent cancer.

As a result, we excise it, and we see cancer. We decided to remove the entire mammary gland, since it still had many small metastases. We carried out chemotherapy and radiation therapy. But at the same 42 years, the woman dies from multiple metastases. I am amazed at how aggressive her illness progressed. Unfortunately, the number of such patients is increasing because they manage to give birth and pass on their genes to their children.

Wasn’t it possible to do something proactive if there was a problem in the family? genetic predisposition? Oncologists say that in the first stages - I AndII degree, from illness emore can be cured.

Yes, it can be cured. But it happens in different ways. There is a huge tumor, but it is sluggish and does not metastasize. For example, I observed a patient. I spent 10 years trying to persuade her to operate on breast cancer. She refused, but the tumor remained as it was, did not grow, did not metastasize. But when a woman developed stomach cancer, I removed both that and that tumor at the same time.

- What types of cancer metastasize?

There are types of cancer, for example, basal cell carcinomas, that do not metastasize. They exist for many years without causing much suffering. On the other hand, sometimes a small tumor can give rise to numerous metastases. Just because we remove this focus, we will not radically cure the patient. You will still need chemotherapy.

In oncology, it is generally accepted that if the cancer does not recur within 10 years, then the disease is considered cured. As a rule, people can be cured Ith AndIIthstages. It is clear that doctorsBysickIVth stage, all that remains is to fight for the quality of life in the last days, weeks or months. But what can be said about people with III stage of the disease?

Firstly, with regard to stages I and II of the disease, not everything is so simple. Yes, as a rule, oncologists combine these stages and call it early cancer.

But in fact, early cancer is Stage I. And stage II is no longer early cancer. For example, stage II of stomach cancer is when the tumor grows through the entire wall of the stomach, or even goes beyond the wall and grows into other organs. What kind of early cancer is this?

Stage III refers to the presence of metastases. The tumor itself may be small, but there are regional areas affected The lymph nodes. All this is radically removed during surgery, but there is a possibility that the tumor will continue to grow.

Now oncologists have a theory that cancer is not a lesion of some organ, but a cancerous disease. There are tumor stem cells in the human body. They circulate in the blood like normal cells. They may not become active for decades.

But at some stage, as a result of decreased immunity, exposure to ionizing radiation or some kind of stress, tumor stem cells begin to actively divide. Their division is like branches on trees. Thus, an array of tumor cells, that is, tumor tissue, grows. We treat a person, remove the tumor, irradiate him, and so on, and the stem tumor cells remain.

That's why we have patients who live to a second and even a third cancer. This speaks, on the one hand, of progress in the treatment of tumors, but on the other hand, there is no cancer of any organ - there is simply a cancer disease.

Hello to all those who are recovering, those who have recovered, and everyone who simply cares about their health!

The reason for my today's post about a blood test for the presence of gene mutations BRCA1 and BRCA2 were prompted by an active discussion on one of the social networks about a photograph of a successful young woman. I won’t name her, both for confidentiality reasons and simply because it’s not important in principle. Just recently she posted a photo with an emphasis on her big breasts. Among the commentators of this photo, a controversy broke out over the naturalness of the breasts. But the owner of that same breast said that she does not hide at all the fact that she has implants. At the same time, she wrote that one of the reasons why she decided to have breast implants was, according to her, breast cancer prevention, just like I did.

And one of the commentators attacked her with sharp criticism:

“Are you serious about Angelina Jolie? What now, if there is breast cancer in the family, you have to get rid of part of your body and get an implant?! Cancer prevention in any form has never saved anyone from cancer! It's not as simple as it seems. Cancer is deep processes in consciousness on a subtle level and only then on a physical level,” this woman wrote.

Honestly, I was horrified that people make such serious statements without studying this issue one bit. It is because of such beliefs that, in many cases where cancer can be prevented, in our country, and throughout the world, people die from oncology, which has long been successfully treated.

And I decided to write this article for all skeptics about any surgical decisions in the breast area :) Modern medicine does not stand still, it develops. It has long been discovered that mutations in the BRCA1 and BRCA2 genes can lead to breast cancer or ovarian cancer.

To begin with, two very important points:

• Before deciding to have surgery, Angelina Jolie underwent a blood test to check for gene mutations BRCA1 and BRCA2. And she was found to have such a BRCA1 gene mutation that the risk of developing breast cancer was 87%, and the risk of ovarian cancer was 50%. Only after this did she decide to have surgery.

• No amount of work at the “subtle level” can change gene mutation. Gene mutation cannot be treated. I don’t know, maybe in the future medicine will be able to treat such mutations. Please do not believe anyone who now offers you to “treat” your genes. These are scammers.

Prophylactic mastectomy- this is one of the effective forms reducing the risk of breast cancer by up to 5-10%, and prophylactic oophorectomy, that is, removal of the ovaries, reduces the risk of cancer by 90%.

It's not easy to make a decision about something like this preventive measures. After all, the female breast is a symbol of femininity and motherhood. But give yourself time. Don't say no right away. Consult in several places. Work with your fears. You may need psychological support.

When I found out about my diagnosis and was undergoing treatment, not a single doctor told me about the possibility of taking a test for gene mutation. Although I was diagnosed with an aggressive form of cancer: triple negative. I don’t know how things are now in oncology clinics; do doctors give enough information to their patients? Consult your doctor about the need for such a test. I hope this post will help you make the right choice regarding treatment.

In what cases is it recommended to undergo a blood test for the presence of mutations in the BRCA1 and BRCA2 genes?

1. Firstly, those who have been diagnosed with triple negative breast cancer;
2. If you were diagnosed with breast cancer before age 40;
3. If you are healthy but have a family history of breast or ovarian cancer.

Typically, studies for the presence of mutations in the BRCA1 and BRCA2 genes take no more than 1 month.

What to do if a mutation of the BRCA1 and BRCA2 genes is detected?

If you, like me, have been diagnosed with a mutation of the BRCA1 and BRCA2 genes, then you should first of all consult with a geneticist, then with your oncologist and choose an action plan depending on the degree of risk, your age, and future plans for having children etc.

It can be:

• regular breast self-examination;
• dynamic observation (regular visits to a mammologist, ultrasound and mammography, etc.);
• taking tamoxifen (an expensive drug with a lot of side effects);
• prophylactic oophorectomy;
• prophylactic mastectomy followed by reconstruction;
• something else depending on the degree of development of medicine in your region.

What's the good news for BRCA1 and BRCA2 gene mutation carriers?

• According to statistics, the survival rate of patients with hereditary cancer of the female reproductive system is significantly higher compared to the general group of patients;
• Even if a mutation is detected in you, this does not mean at all that the process will ever be started in your body, 70-90% is not yet 100%. You always have the remaining 10-30%.
• You can develop high resistance to stress, work with your fears, or simply pray to a higher power to grant you health. The choice is yours. 🙂 No one can force you to have a mastectomy.

Where can I get a mutation test?

I know that for the purpose of early detection of breast, ovarian and prostate cancer, the Moscow Department of Health and the Moscow Clinical science Center them. S.A. Loginova DZM every Saturday from July 7 to September 22, 2018(from 8.00 to 14.00) carries out a screening program (completely FREE).

To take the analysis, you must have your passport with you and give consent to the processing of personal data (provide a reliable method of feedback).

• Preliminary preparation for donating blood for BRCA1 and BRCA2 is not required for women (over 18 years of age).
• Men over 40 years of age can take a PSA blood test to check for a predisposition to prostate cancer: it is advisable to abstain from sexual activity 2 days before the test. Half an hour before blood sampling, physical overexertion should be avoided.

The analysis is carried out by drawing blood from a vein.

You have 10 more days to complete this analysis completely free of charge!

Here you can download the schedule and addresses for cancer screening.

But, even if you read this post after 09.22.18, I am sure that the Department of Health will still carry out such actions. Medical organizations Health Departments have been holding similar events for several years now, deploying mobile medical units in various areas of the city and in places of public events. Follow the news.

Well, if you didn’t have time, this analysis can be done in any paid laboratory. Perhaps in simple public hospitals Soon they will be doing such analyzes on an ongoing basis.

If family members in one or several generations have one type of tumor or have different types in two or more close relatives, as well as if a patient’s tumor affects paired organs, there is a need to check for the presence of certain genetic changes that can be inherited. Genetic testing is also indicated for people who have had cancer in childhood and were born with a tumor and developmental defects. Such studies make it possible to find out whether there are hereditary causes for the occurrence of cancer in this family and to determine the likelihood of the tumor occurring in close relatives.

Currently, ideas about the genetic nature of development are based on the assumption of the existence of genes whose normal function is associated with the suppression of tumor growth. Such genes were called tumor suppressor genes. Defects in these genes lead to progression, and restoration of function leads to a significant slowdown in proliferation or even reversal of tumor development.

Here are some examples of such genetic changes.

The best known of these genes is RB1 gene. Mutations of two genes , have an almost equal contribution to the occurrence of hereditary forms of breast cancer (5%). Also mutations mutations BRCA1 increase the risk of ovarian cancer, and mutations BRCA2 predispose to breast cancer in men and pancreatic cancer.

The hereditary form of nonpolyposis develops as a result of mutations in genes MSH2 And MLH1. Women who have a mutation in one of these genes are most likely to develop ovarian and endometrial cancer.

Mutation in germ cells (germinal) in one of the alleles of the gene RB1 leads to predisposition to retinoblastoma. Also, patients with a similar mutation have a high risk of developing tumors such as osteosarcoma, lymphocytic leukemia, SCLC, breast cancer, tumors of the genital organs, so patients with a hereditary form of the disease need to be monitored. Mutations of this gene in somatic cells cause only retinoblastoma, although dysfunction RB1 found in many other tumors, but as secondary ones, which are a sign of genome destabilization.

Germinal mutations of the suppressor gene CDKN2A/p16 cause hereditary forms of melanoma, dysplastic nevus syndrome and atypical moles, pancreatic tumors, head and neck tumors. When a suppressor gene is inactivated WT1 nephroblastoma may occur (this is the cause of about a third of all nephroblastomas), and uniform damage by mutation of the entire suppressor gene PTEN leads to cancer of the breast, prostate, ovaries, endometrium, and thyroid gland.