Advertising on the portal

What is a mutation in oncology? The role of genetic factors in the development of specific types of cancer

Deletion Some genes can lead to dysregulation of cell growth, so that if they are in a homozygous state, it can lead to the development of cancer. The bcr gene, together with its translocation partner, forms a complex protein that causes constant expression of the enzyme tyrosine kinase, a stimulator of cell division.

For deactivations tumor suppressor gene damage is required in both alleles of the gene, therefore such a recessive mechanism is characteristic of hereditary forms of cancer, when congenital damage or deletion in one of the alleles is supplemented during life by damage to the paired allele, which leads to the development of a tumor. The table shows the characteristic features of tumor suppressing genes that distinguish them from oncogenes.

Among the most studied diseases This type includes Li-Fraumeni syndrome and Wilms tumor. Nadson proposed that retinoblastoma develops in two stages, with the loss of the inherited allele occurring after the loss of the complementary allele. Apparently, the loss of the second allele occurs during the process of recombination or mitotic chromosome nondisjunction.

In patients retinoblastoma The risk of developing osteosarcoma increases 300 times. It is still not clear why these tumors are so strictly restricted to these two locations (bone and eye). The Rb gene is located on chromosome 13ql4.

Distinctive features of oncogenes and tumor suppressor genes

The Wilma tumor gene is located in 11p13 chromosome, and, as with retinoblastoma, the absence of this gene is periodically reported in patients with non-hereditary cancers such as osteosarcoma. Inherited forms of Wilma tumor are quite rare, and 50% of people with damage to this gene do not develop tumors. However, in some patients with non-hereditary forms, a deletion of the 11p13 chain is registered, and studies of polymorphism of the chromosome set show the loss of this chromosomal region in 50% of patients.

Development Li-Fraumeni syndrome caused by a congenital mutation of the p53 gene. In families with this mutation, there is a risk of sarcoma in childhood, early development of breast cancer in the female half, and an increased risk of brain cancer, adrenal cancer and leukemia in all family members. The p53 protein is a nuclear phosphoprotein that regulates the cell cycle. Its sporadic mutations are often observed in cancers of various types.

BRCA1 genes And BRCA2 are tumor suppressor genes for breast cancer. Congenital mutations are transmitted by maternal and paternal chromosomes 17 and 13, respectively. Subsequent loss of the healthy allele results in inactivation of the gene. Both of these genes encode proteins responsible for DNA repair and maintaining the integrity of the cell genome.

The loss of their activity leads to accumulation of genetic errors and, as a consequence, to the development of cancer. Men with mutations in these genes have an increased risk of developing prostate cancer.

Scientists today know that the process of cancer growth begins when one or more genes in a cell undergo a mutation process. 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 periods of 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 in throughout life, and the altered gene will be contained only in the descendant cells 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 of malignant neoplasms are hereditary, 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 transmitted from parents to a child, it is present in every cell of the child’s body, including the cells of the reproductive system - sperm or eggs, and can be 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. 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 types of inheritance: dominant, when one inherited copy of the gene is enough to develop 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, meaning gene damage 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%. The presence of a cancer mutation in the genome 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 old age) and the second most common cause of death 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 established in 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 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 be at increased risk of developing breast cancer or other cancers. 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 lifetime risk of developing breast cancer, ranging from 25% to 50%, and a 65% risk of benign breast tumors. 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. With Cowden syndrome, the likelihood of developing cancer and benign tumors of the thyroid gland is increased. 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 PCY 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 for developing cancer, you should discuss your family medical history and personal risk factors with your doctor. Those people who are at increased risk of developing breast cancer can undergo special genetic testing and follow their individual early diagnosis plan. 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, excess weight, 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 female cancer diseases and 5th among the causes 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 inherited 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 breast and ovarian cancer. 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 is synthesized that is involved in the cell cycle and limits 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 of 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, breast ultrasound 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 cancers of the stomach, 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. The most common causes of the 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 HNPTC 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 NNPTC 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, spider veins called telangiectasia, which are dilated capillaries, are noticeable on the skin, mucous membranes and sclera of the eyes. Patients with this syndrome also have a weakened immune system and are susceptible to infections. 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 ranging in color from white to bright pink, located on the eyelids, ear 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 strategy. 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 development in patients with FHL syndrome are the eyes (retinal angiomas), brain and spinal cord (hemangioblastomas), adrenal glands (pheochromocytoma) and inner ear (endolymphatic sac tumors). 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 is recommended for individuals 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 an early age. This screening includes:
    • Eye examination and blood pressure monitoring from age 5 years;
    • Ultrasound of the abdominal organs from early childhood, MRI or CT scan 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, the genetic causes of kidney cancer are not yet known. For family members with these rare syndromes, it is recommended that screening for kidney tumors begin at age 20 using ultrasound, MRI, or retroperitoneal CT.
  • 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 a hereditary history of SPPCC should undergo screening diagnostic tests, 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. At present, special methods have already been developed to detect 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 scan starting at 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 rates of kidney cancer?

Clinical observations show that there are other cases of familial predisposition to the development of kidney tumors, and this topic has received 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 prostate cancer

Most people are of the opinion that there is no disease worse than cancer. Any doctor is ready to challenge this idea, but public opinion is a conservative thing.

And despite the fact that oncological pathology occupies an honorable third place among the causes of disability and death, people will continue to believe for a very long time that there is no disease more terrible and will look for ways to avoid oncology.

It is known that any disease is cheaper and easier to prevent than to treat, and cancer is no exception. And the treatment itself, started at an early stage of the disease, is many times more effective than in advanced cases.

Basic postulates that will allow you not to die from cancer:

  • Reducing exposure to carcinogens on the body. Any person, having removed at least some of the oncogenic factors from his life, is able to reduce the risk of cancer pathology by at least 3 times.
  • The catchphrase “all diseases are from the nerves” is no exception for oncology. Stress is a trigger for the active growth of cancer cells. Therefore, avoid nervous shocks, learn to deal with stress - meditation, yoga, a positive attitude towards what is happening, the “Key” method and other psychological training and attitudes.
  • Early diagnosis and early treatment. believes that cancer detected at an early stage is curable in more than 90% of cases.

Mechanism of tumor development

Cancer in its development goes through three stages:

The origin of cell mutation - initiation

In the process of life, the cells of our tissues constantly divide, replacing dead or spent ones. During division, genetic errors (mutations) and “cell defects” may occur. A mutation causes a permanent change in a cell's genes, affecting its DNA. Such cells do not turn into normal ones, but begin to divide uncontrollably (in the presence of predisposing factors), forming a cancerous tumor. The causes of mutations are as follows:

  • Internal: genetic abnormalities, hormonal imbalances, etc.
  • External: radiation, smoking, heavy metals, etc.

The World Health Organization (WHO) believes that 90% of cancer diseases occur due to external causes. Factors of the external or internal environment, the impact of which can cause cancer and promote tumor growth, are called CARCINOGENS.

The entire stage of the birth of such cells can take several minutes - this is the time of absorption of the carcinogen into the blood, its delivery to the cells, attachment to DNA and transition to the state of an active substance. The process is completed when new daughter cells with a changed genetic structure are formed - that’s it!

And this is already irreversible (with rare exceptions), see. But, at this point, the process may stop until favorable conditions are created for the further growth of a colony of cancer cells, since the immune system does not sleep and fights such mutated cells. That is, when the immune system is weakened - severe stress (most often this is the loss of loved ones), a serious infectious disease, as well as in case of hormonal imbalance, after an injury (see), etc. - the body is unable to cope with their growth, then 2 stage.

The presence of favorable conditions for the growth of mutating cells - promotion

This is a much longer period (years, even decades) when newly mutated cancer-prone cells are ready to multiply into a noticeable cancerous tumor. It is precisely this stage that can be reversible, since everything depends on whether the cancer cells are provided with the necessary conditions for growth. There are many different versions and theories of the causes of cancer development, among which is the connection between the growth of mutated cells and human nutrition.

For example, the authors T. Campbell, K. Campbell in the book “Chinese Study, Results of the Largest Study of the Connection between Nutrition and Health,” present the results of 35 years of research into the connection between oncology and the predominance of protein foods in the diet. They argue that the presence of more than 20% animal proteins in the daily diet (meat, fish, poultry, eggs, dairy products) contributes to the intensive growth of cancer cells, and vice versa, the presence of antistimulants in the daily diet (plant foods without heat or cooking) slow down and even stops their growth.

According to this theory, you should be very careful with the various protein diets that are fashionable today. Nutrition should be complete, with an abundance of vegetables and fruits. If a person with stage 0-1 cancer (without knowing it) “sits” on a protein diet (for example, in order to lose weight), he essentially feeds cancer cells.

Development and growth - progression

The third stage is the progressive growth of a group of formed cancer cells, the conquest of neighboring and distant tissues, that is, the development of metastases. This process is irreversible, but it is also possible to slow it down.

Causes of carcinogenesis

WHO divides carcinogens into 3 large groups:

  • Physical
  • Chemical
  • Biological

Science knows thousands of physical, chemical and biological factors that can cause cellular mutations. However, only those whose action is RELIABLY associated with the occurrence of tumors can be considered carcinogens. This reliability must be ensured by clinical, epidemiological and other studies. Therefore, there is the concept of “potential carcinogen”, this is a certain factor whose action can theoretically increase the risk of developing cancer, but its role in carcinogenesis has not been studied or proven.

Physical carcinogens

This group of carcinogens mainly includes various types of radiation.

Ionizing radiation

Scientists have known for a long time that radiation can cause genetic mutations (Nobel Prize 1946, Joseph Möller), but convincing evidence of the role of radiation in the development of tumors was obtained after studying victims of the nuclear bombings of Hiroshima and Nagasaki.

The main sources of ionizing radiation for modern man are as follows.

  • Natural radioactive background – 75%
  • Medical procedures – 20%
  • Other – 5%. Among other things, there are radionuclides that ended up in the environment as a result of ground tests of nuclear weapons in the middle of the 20th century, as well as those that got into it after man-made disasters in Chernobyl and Fukushima.

It is useless to influence the natural radioactive background. Modern science does not know whether a person can live completely without radiation. Therefore, you should not trust people who advise reducing the concentration of radon in the house (50% of the natural background) or protecting yourself from cosmic rays.

X-ray examinations carried out for medical purposes are another matter.

In the USSR, fluorography of the lungs (to detect tuberculosis) had to be performed once every 3 years. In most CIS countries, this examination is required annually. This measure reduced the spread of tuberculosis, but how did it affect the overall cancer incidence? There is probably no answer, because no one has addressed this issue.

Also, computed tomography is very popular among ordinary people. At the patient’s insistence, it is done to whoever needs it and who doesn’t need it. However, most people forget that CT is also an x-ray examination, only more technologically advanced. The radiation dose from a CT scan is 5 to 10 times higher than a regular x-ray (see). We are in no way calling for abandoning x-ray examinations. You just need to approach their purpose very carefully.

However, there are still force majeure circumstances, such as:

  • life in premises built from or decorated with emission-producing materials
  • life under high voltage lines
  • submarine service
  • work as a radiologist, etc.

Ultraviolet radiation

It is believed that the fashion for tanning was introduced in the mid-twentieth century by Coco Chanel. However, back in the 19th century, scientists knew that constant exposure to sunlight ages the skin. It’s not for nothing that rural residents look older than their urban peers. They spend more time in the sun.

Ultraviolet radiation causes skin cancer, this is a proven fact (WHO report 1994). But artificial ultraviolet light - solarium - is especially dangerous. In 2003, WHO published a report on concerns about tanning beds and the irresponsibility of manufacturers of these devices. Solariums are prohibited for persons under 18 years of age in Germany, France, Great Britain, Belgium, the USA, and in Australia and Brazil they are completely prohibited. So a bronze tan is probably beautiful, but not at all useful.

Local irritant effect

Chronic trauma to the skin and mucous membranes can cause tumor development. Poor quality dentures can cause lip cancer, and constant friction of clothing against a birthmark can cause melanoma. Not every mole becomes cancer. But if it is in an area of ​​increased risk of injury (on the neck - collar friction, on the face in men - injury from shaving, etc.) you should think about removing it.

Irritation can also be thermal and chemical. Those who eat very hot food put themselves at risk of cancer of the mouth, pharynx and esophagus. Alcohol has an irritating effect, so people who prefer strong strong drinks, as well as alcohol, are at risk of developing stomach cancer.

Household electromagnetic radiation

We are talking about radiation from cell phones, microwave ovens and Wi-Fi routers.

WHO has officially classified cell phones as potential carcinogens. Information about the carcinogenicity of microwaves is only theoretical, and there is no information at all about the effect of Wi-Fi on tumor growth. Quite the contrary, there are more studies demonstrating the safety of these devices than there are fabrications about their harm.

Chemical carcinogens

The International Agency for Research on Cancer (IARC) divides substances used in everyday life and in industry, according to their carcinogenicity, into the following groups (information is provided as of 2004):

  • Reliably carcinogenic– 82 substances. Chemical agents whose carcinogenicity is beyond doubt.
  • Probably carcinogenic– 65 substances. Chemical agents whose carcinogenicity has a very high degree of evidence.
    Possibly carcinogenic– 255 substances. Chemical agents whose carcinogenicity is possible, but questioned.
  • Probably non-carcinogenic– 475 substances. There is no evidence that these substances are carcinogenic.
  • Reliably non-carcinogenic- chemical agents proven not to cause cancer. So far there is only one substance in this group – caprolactam.

Let's discuss the most significant chemicals that cause tumors.

Polycyclic aromatic hydrocarbons (PAHs)

This is a large group of chemicals formed during incomplete combustion of organic products. Contained in tobacco smoke, exhaust gases from cars and thermal power plants, stove and other soot, formed during frying food and heat treatment of oil.

Nitrates, nitrites, nitroso compounds

It is a by-product of modern agrochemicals. Nitrates themselves are completely harmless, but over time, as well as as a result of metabolism in the human body, they can turn into nitroso compounds, which in turn are very carcinogenic.

Dioxins

These are chlorine-containing compounds, which are waste from chemical and oil refining industries. May be part of transformer oils, pesticides and herbicides. They can appear when burning household waste, in particular plastic bottles or plastic packaging. Dioxins are extremely resistant to destruction, so they can accumulate in the environment and the human body; fatty tissue especially “loves” dioxins. It is possible to minimize the entry of dioxidins into food if:

  • do not freeze food or water in plastic bottles - this way toxins easily penetrate into the water and food
  • Do not heat food in plastic containers in the microwave; it is better to use tempered glass or ceramic containers
  • Do not cover food with plastic wrap when heating it in the microwave; it is better to cover it with a paper napkin.

Heavy metals

Metals with a density greater than iron. There are about 40 of them in the periodic table, but the most dangerous for humans are mercury, cadmium, lead, and arsenic. These substances enter the environment from waste from mining, steel, and chemical industries; a certain amount of heavy metals is contained in tobacco smoke and car exhaust gases.

Asbestos

This is the general name for a group of fine-fiber materials containing silicates as a base. Asbestos itself is completely safe, but its smallest fibers entering the air cause an inadequate reaction of the epithelium with which they come into contact, causing oncology of any organ, but most often it causes the larynx.

An example from the practice of a local therapist: in a house built from asbestos exported from East Germany (rejected in this country), the cancer statistics are 3 times higher than in other houses. This feature of the “phoning” building material was reported by the foreman who worked during the construction of this house (she died of breast cancer after an already operated sarcoma of her toe).

Alcohol

According to scientific research, alcohol does not have a direct carcinogenic effect. However, it can act as a chronic chemical irritant to the epithelium of the mouth, pharynx, esophagus and stomach, promoting the development of tumors in them. Strong alcoholic drinks (over 40 degrees) are especially dangerous. Therefore, those who like to drink alcohol are not only at risk.

Some ways to avoid exposure to chemical carcinogens

Oncogenic chemicals can affect our body in different ways:

Carcinogens in drinking water

According to Rospotrebnadzor data, up to 30% of natural reservoirs contain prohibitive concentrations of substances hazardous to humans. Also, do not forget about intestinal infections: cholera, dysentery, hepatitis A, etc. Therefore, it is better not to drink water from natural reservoirs, even boiled.

Old, worn-out water supply systems (of which up to 70% in the CIS) can cause carcinogens from the soil to enter drinking water, namely nitrates, heavy metals, pesticides, dioxins, etc. The best way to protect yourself from them is to use household water purification systems, and Also ensure the timely replacement of filters in these devices.

Water from natural sources (wells, springs, etc.) cannot be considered safe, since the soil through which it passes can contain anything - from pesticides and nitrates, to radioactive isotopes and chemical warfare agents.

Carcinogens in the air

The main oncogenic factors in the inhaled air are tobacco smoke, car exhaust gases and asbestos fibers. To avoid breathing carcinogens you need to:

  • Quit smoking and avoid secondhand smoke.
  • City residents should spend less time outdoors on a hot, windless day.
  • Avoid using building materials containing asbestos.

Carcinogens in food

Polycyclic hydrocarbons appear in meat and fish with significant overheating, that is, during frying, especially in fat. Reusing cooking fats significantly increases their PAH content, so domestic and industrial deep fryers are an excellent source of carcinogens. Not only French fries, whites or fried pies bought at a stall on the street are dangerous, but also barbecue prepared with your own hands (see).

Special mention should be made about the kebab. The meat for this dish is cooked over hot coals, when there is no longer any smoke, so PAHs do not accumulate in it. The main thing is to make sure that the kebab does not burn and not to use ignition products in the grill, especially those containing diesel fuel.

  • Large amounts of PAHs appear in food when smoked.
  • It is estimated that 50 grams of smoked sausage can contain as many carcinogens as the smoke from a pack of cigarettes.
  • A jar of sprat will reward your body with carcinogens from 60 packs.

Heterocyclic amines appear in meat and fish during prolonged overheating. The higher the temperature and the longer the cooking time, the more carcinogens appear in the meat. An excellent source of heterocyclic amines is grilled chicken. Also, meat cooked in a pressure cooker will contain more carcinogens than simply boiled meat, since in a hermetically sealed container the liquid boils at a much higher temperature than in air - use a pressure cooker less often.

Nitroso compounds spontaneously form in vegetables, fruits and meat from nitrates at room temperature. Smoking, roasting and canning greatly enhance this process. On the contrary, low temperatures inhibit the formation of nitroso compounds. Therefore, store vegetables and fruits in the refrigerator, and also try to eat them raw whenever possible.

Carcinogens in everyday life

The main component of cheap detergents (shampoos, soaps, shower gels, bath foams, etc.) is sodium lauryl sulfate (Sodium Lauryl Sulfate -SLS or Sodium Laureth Sulfate - SLES). Some experts consider it to be oncogenically dangerous. Lauryl sulfate reacts with many components of cosmetic preparations, resulting in the formation of carcinogenic nitroso compounds (see).

The main source of mycotoxins is the “toad”, which “strangles” the housewife when she sees slightly rotten cheese, bread or a small spot of mold on jam. Such products must be thrown away, since removing mold from food only saves you from eating the fungus itself, but not from the aflatoxins that it has already released.

On the contrary, low temperatures slow down the release of mycotoxins, so greater use of refrigerators and cold cellars should be made. Also, do not eat rotten vegetables and fruits, as well as products with expired expiration dates.

Viruses

Viruses that can transform infected cells into cancer cells are called oncogenic. These include.

  • Epstein-Barr virus – causes lymphomas
  • Hepatitis B and C viruses can cause liver cancer
  • Human papillomavirus (HPV) is a source of cervical cancer

In fact, there are much more oncogenic viruses; only those whose influence on tumor growth has been proven are listed here.

Vaccines can provide protection against some viruses, for example, against hepatitis B or HPV. Many oncogenic viruses are sexually transmitted (HPV, hepatitis B), therefore, in order not to give yourself cancer, you should avoid sexually risky behavior.

How to avoid exposure to carcinogens

From all that has been said, several simple recommendations follow that will significantly reduce the influence of oncogenic factors on your body.

  • Stop smoking.
  • How women can avoid breast cancer: have children and breastfeed for a long time, refuse hormone replacement therapy in postmenopause.
  • Drink only high-quality alcohol, preferably not very strong.
  • Do not overuse your beach holiday; avoid visiting the solarium.
  • Don't eat very hot food.
  • Eat less fried and grilled foods, and do not reuse fat from frying pans and deep fryers. Give preference to boiled and stewed foods.
  • Make more use of your refrigerator. Do not purchase products from dubious places and markets, monitor their expiration dates.
  • Drink only clean water, use household water purification filters more widely (see).
  • Reduce the use of cheap cosmetics and personal hygiene products and household chemicals (see).
  • When carrying out finishing work at home and in the office, give preference to natural building materials.

How to avoid getting cancer? Let us repeat - if you remove at least some carcinogens from your everyday life, you can reduce the risk of cancer by 3 times.

To defeat cancer that is resistant to conventional chemotherapy, it is necessary to turn on an alternative self-destruction scenario in cancer cells.

Drug resistance in cancer cells is usually attributed to new mutations. For example, after a mutation, a cell becomes invisible to drug molecules - the drug stops interacting with some receptor protein on the cell, or cancer cells, after new genetic changes, find a workaround for important processes that chemotherapy turned off in them; The scenarios here may be different.

Usually in such cases they try to create a new drug that would act taking into account the new mutation; it turns out to be something like a constant arms race. However, cancer has another strategy with which it is able to escape from drug attack, and this strategy is not associated with mutations, but with the normal ability of cells to adapt to environmental conditions. This ability is called plasticity: no changes occur in the genetic text, just signals from the external environment change the activity of genes - some begin to work stronger, some weaker.

Typically, anti-cancer drugs cause a cell to enter apoptosis, or a suicide program where the cell destroys itself with minimal harm to others. Cancer cells, due to plasticity, can go into a state where it becomes very, very difficult to turn on their apoptosis program with anything.

We can explain what is happening here like this: imagine that the cell has a switch that turns on apoptosis, and there is a hand that pulls the switch. In the case of mutational drug resistance, the switch changes shape so much that you can no longer grasp it with your hand; and in the case of stability due to plasticity, you can grab hold of this switch, but it becomes so tight that there is no way to turn it.

The fact that cancer cells can, so to speak, suppress their suicidal desires has been known for a relatively long time, but the question remained of how effective such a trick was. Researchers believe that it is effective, and even very effective.

They analyzed gene activity in several hundred types of cancer cells and came to the conclusion that the more clearly the “anti-suicide” genes worked in the cells, the more resistant they were to drugs. In other words, there is a direct relationship between cellular plasticity and the ability to resist drugs.

Moreover, it turns out that cells use this tactic with variations, that the non-self-destruction tactic is turned on in many, if not all, types of cancer, and that it is turned on regardless of the specific therapy. That is, non-mutational drug resistance has turned out to be a universal and widespread way of dealing with difficulties among malignant cells. (Recall that metastases scatter throughout the body not so much because of new mutations that encourage cancer cells to wander, but because of.)

The question arises: does it make sense in this case to use medications at all, since there is such an absolute shield against them? But every defense has a weak point, and in the article in Nature The authors of the work say that cells resistant to apoptosis can be killed using ferroptosis.

Cells can die according to different scenarios - according to the scenario of apoptosis, necroptosis, pyroptosis, etc., and ferroptosis, which was discovered relatively recently, is one of them. From the name it is clear that the main role here is played by iron: under certain conditions and in the presence of iron ions in the cell, the lipids that make up the membranes begin to oxidize; Toxic oxidation products appear in the cell, membranes begin to deteriorate, so that in the end the cell chooses to die itself.

Ferroptosis, like everything else, depends on different genes, and the authors of the work managed to find the gene through which it is best to act here - this is the gene GPX4, encoding the enzyme glutathione peroxidase. It protects cellular lipids from oxidation, and if it is turned off, ferroptosis will inevitably begin in the cell. Disabling GPX4, it is possible to suppress the growth of a wide variety of tumor cells, from lung cancer to prostate cancer, from pancreatic cancer to melanoma.

All this once again suggests that malignant diseases require complex treatment - cancer cells have a lot of tricks to help them survive. On the other hand, since it does not always all come down to new mutations, one can hope that effective therapy for the patient can be selected without a thorough genetic analysis.


What causes one patient's cancer disease to be more aggressive than another? Why do some people have cancer that is resistant to chemotherapy? A genetic mutation of the MAD2 protein may help answer both of these questions.

Researchers engineered an inherited mutation in the MAD2 gene in human cancer cells, which is responsible for the process of cancer cell division and proliferation. As a result, the mutation made the tumor cells that were born from existing ones very variable in their properties, which by all indications had characteristics consistent with more aggressive forms of cancer. In addition, the newborn mutated cancer cells were resistant to toxins (chemotherapy). The results of this study, published in the January 18 issue of the journal Nature, have important implications for the development of new drugs and could help create a new “marker gene” to diagnose the aggressiveness of tumors and detect them at an early stage.

Back in 1996, Dr. Robert Benezra and Yong Lee identified the MAD2 gene as a class of proteins responsible for some of the functions of division and budding of newborn cancer cells from the uterine cell. They ensure even distribution of chromosomes to the two daughter cells during the process of cell division. The loss of this normal division mechanism leads to unstable forms in which entire chains of chromosomes can be lost or extra ones added. Cancers that exhibit this type of chromosome instability are usually more aggressive and have an uncertain prognosis regarding the patient's future life prospects. Correlations between chromosome instability and MAD2 loss have been identified in human colon cancer cells. However, previously there was no evidence that there is a connection between these phenomena. Now, scientists know that the loss of MAD2 on maternal cancer cells creates chromosomal instability for newborn cancer cells.

For example, mice with a complete absence of the MAD2 gene die during embryonic development. Even one copy of the MAD2 gene led to the development of cancer in mice. Uniquely, this mutation led to the development of lung cancer in mice, despite the fact that the disease is extremely rare in them. Why this affected lung tissue is not yet known, but it does show that MAD2 is involved in cancer development.

The opinions of a number of other specialists in this field on the results of this study indicate other fundamental possibilities that help explain the reasons for the effectiveness of cancer treatment in some and the ineffectiveness, and sometimes even negative effects of chemotherapy in others.

In particular, one patient with cancer has, for example, unstable and prone to mutations (due to the weakness of the MAD2 gene) cancer cells of a certain type, and another has the same form of cancer, but with resistant forms. Thus, chemotherapy treatment for the first patient will most likely have no effect in destroying the tumor or slowing its growth, and may even cause an accelerated response to further cancer progression. At the same time, in another patient, a course of chemotherapy can have a positive effect and even lead to recovery.

The latter circumstance is extremely rare, which may indicate that the majority of people with cancer have unstable forms of cancer cells, which are sometimes simply impossible to influence in combination with various types of therapies. Unstable forms appear to exist due to the main factors that become the causes of the development of cancer. As a rule, these are carcinogens and poisons with which modern civilization poisons itself. That is, cancer cells themselves undergo constant mutations, just as healthy cells develop into malignant ones due to mutations.

Probably for the same reason, no solution has yet been found to combat this deadly disease, which is the second leading cause of death after cardiovascular diseases.