Cancer dna analysis of love. Hereditary predisposition to cancer. Combination of DNA errors and external factors

The high incidence of cancer forces oncologists to work daily on issues of early diagnosis and effective treatment. Genetic analysis for cancer This is one of the modern methods of cancer prevention. However, is this study so reliable and should it be prescribed to everyone? is a question that worries scientists, doctors, and patients.

Indications

Today, genetic analysis for cancer allows you to identify the risk of developing oncopathologies:

• mammary gland;
• ovaries;
• cervix;
• prostate;
• lungs;
• intestines and colon in particular.

Also, there is a genetic diagnosis for some congenital syndromes, the existence of which increases the likelihood of developing cancer in several organs. For example, Li-Fraumeni syndrome indicates the risk of adrenal glands, pancreas and blood, and Peutz-Jeghers syndrome indicates the likelihood of oncopathologies of the digestive system (esophagus, stomach, intestines, liver, pancreas).

What does such an analysis show?

To date, scientists have discovered a number of genes, changes in which in most cases lead to the development of oncology. Every day, dozens of malignant cells develop in our body, but the immune system, thanks to special genes, is able to cope with them. And with breakdowns in certain DNA structures, these genes do not work correctly, which gives a chance for the development of oncology.

So, the BRCA1 and BRCA2 genes protect women from developing ovarian and breast cancer, and men from. Breakdowns in these genes, on the contrary, show that there is a risk of developing carcinoma of this localization. An analysis for a genetic predisposition to cancer just provides information about changes in these and other genes.

Breakdowns in these genes are inherited. Everyone knows the case of Angelina Jolie. Her family had a case of breast cancer, so the actress decided to undergo a genetic diagnosis, which revealed mutations in the BRCA1 and BRCA2 genes. True, the only thing the doctors could help in this case was to perform an operation to remove the breast and ovaries so that there was no point of application for the mutated genes.

Are there any contraindications to the test?

There are no contraindications to the delivery of this analysis. However, it should not be done as a routine examination and equated with a blood test. After all, it is not known how the result of the diagnosis will affect the psychological state of the patient. Therefore, an analysis should be prescribed only if there are strict indications for this, namely, registered cases of cancer in blood relatives or if the patient has a precancerous condition (for example, a benign breast lesion).

How is the analysis carried out and do I need to prepare somehow?

Genetic analysis is quite simple for the patient, as it is carried out by a single blood sampling. After the blood is subjected to molecular genetic testing, which allows you to determine mutations in the genes.

There are several reagents specific to a particular structure in the laboratory. In one blood draw, a test for breakdowns in several genes can be carried out.

The study does not require special preparation, however, it will not hurt to follow the generally accepted rules when donating blood. These requirements include:

1. Exclusion of alcohol a week before the diagnosis.
2. Do not smoke for 3-5 days before donating blood.
3. Do not eat 10 hours before the examination.
4. For 3-5 days before donating blood, follow a diet with the exception of fatty, spicy and smoked foods.

How reliable is this analysis?

The most studied is the detection of breakdowns in the BRCA1 and BRCA2 genes. However, over time, doctors began to notice that years of genetic research did not significantly affect the mortality of women from breast and ovarian cancer. Therefore, as a screening diagnostic method (performed by each person), the method is not suitable. And as a survey of risk groups, genetic diagnosis takes place.

The main focus of the analysis on the genetic predisposition to cancer is that if a particular gene breaks down, a person has or is at risk of passing this gene to their children.

Whether or not to trust the results obtained is a personal matter for each patient. Perhaps, if the result is negative, preventive treatment (removal of the organ) should not be carried out. However, if breakdowns in the genes are found, then it is definitely worth closely monitoring your health and regularly conducting preventive diagnostics.

Sensitivity and specificity of the analysis for genetic predisposition to oncology

Sensitivity and specificity are concepts that indicate the validity of a test. Sensitivity tells you what percentage of patients with a defective gene will be detected by this test. And the specificity indicator indicates that with the help of this test, exactly the gene breakdown that encodes a predisposition to oncology, and not to other diseases, will be detected.

Determining percentages for the genetic diagnosis of cancer is quite difficult, since there are many cases of positive and negative results to be investigated. Perhaps later, scientists will be able to answer this question, but today it can be said with certainty that the survey has high sensitivity and specificity, and its results can be relied upon.

The received answer cannot 100% assure the patient that he will get sick or not get cancer. A negative genetic test result indicates that the risk of developing cancer does not exceed the average in the population. A positive answer gives more accurate information. Thus, in women with mutations in the BRCA1 and BRCA2 genes, the risk is 60-90%, and 40-60%.

When and to whom is it appropriate to take this analysis?

This analysis does not have clear indications for delivery, whether it be a certain age or the state of health of the patient. If the mother of a 20-year-old girl was diagnosed with breast cancer, then she should not wait 10 or 20 years to be examined. It is recommended to immediately undergo a genetic test for cancer in order to confirm or exclude the mutation of genes encoding the development of oncopathologies.

Regarding prostate tumors, every man over 50 years of age with prostate adenoma or chronic prostatitis will benefit from genetic diagnosis in order to also assess the risk. But it is most likely inappropriate to perform diagnostics on people whose families did not have cases of a malignant disease.

Indications for genetic analysis for cancer are cases of detection of malignant neoplasms in blood relatives. And an examination should be prescribed by a geneticist, who will then evaluate the result. The age of the patient for taking the test does not matter, since the breakdown in the genes is inherent from birth, so if at the age of 20 the BRCA1 and BRCA2 genes are normal, then it makes no sense to perform the same study after 10 years or more.

Factors distorting the results of the analysis

With proper diagnosis, there are no exogenous factors that can affect the result. However, in a small number of patients during the examination, genetic damage may be detected, the interpretation of which is impossible due to insufficient knowledge. And in combination with unknown changes with mutations in cancer genes, they can affect the test result (i.e., the specificity of the method is reduced).

Interpretation of results and norms

Genetic testing for cancer is not a rule-of-thumb test, and you should not expect a patient to get a result that clearly states “low”, “medium”, or “high” risk of developing cancer. The results of the examination can only be evaluated by a geneticist. The patient's family history influences the final conclusion:

1. The development of malignant pathologies in relatives under 50 years of age.
2. The occurrence of tumors of the same localization in several generations.
3. Repeated cases of cancer in the same person.

How much does such an analysis cost?

Today, such diagnostics are not paid by insurance companies and funds, so the patient has to bear all the expenses.

In Ukraine, the study of one mutation costs about 250 UAH. However, several mutations must be investigated for the validity of the data. For example, for breast and ovarian cancer, 7 mutations (UAH 1,750) are being investigated, for lung cancer – 4 mutations (UAH 1,000).

In Russia, a genetic analysis for breast and ovarian cancer costs about 4,500 rubles.

In September, the Atlas Medical Center opened in Moscow, which specializes in "personalized" and "preventive" medicine. The center offers its patients to first make a screening test "My Genetics", and then develop a prevention and treatment plan based on its results - identified predispositions and risks of diseases, as well as genetically determined reactions to drugs.

Mass sequencing of the genome was started in Russia back in 2007, so there are already several similar companies on the market. However, Atlas has stated that its goal is to make genotyping popular and accessible, much like 23andMe, the American company of Sergey Brin's ex-wife Anna Wojcicki, in which Google has invested nearly $4 million, did. The popularity of 23andMe obviously haunts the owners of Atlas, so they even registered the domain 23&me.ru for themselves.

The creators of the test promise not only to assess the predisposition to 114 and determine the carrier status of 155 hereditary diseases, but also to reveal the secret of origin, give recommendations on nutrition and sports, and provide a free consultation with a geneticist who will tell you how to live with the information received. The My Genetics test costs 14,900 rubles, which is on average two times less than the cost of a similar test from competitors in Russia. The brochures of genotyping companies look promising, but few people understand what kind of information they will get their hands on by handing over their DNA, and how it can then be applied in real life.

The Village asked Alexandra Sheveleva to do a genetic test and tell readers about the results.

Sasha Sheveleva

Man is attracted by self-knowledge. Divination by hand, natal chart, genealogical research, diet by blood type - I want to know exactly who I am, where I come from, how I differ from others and whether I have successful relatives in New Guinea. Therefore, it was terribly interesting to find out what my genes would tell about me.

To donate a piece of your DNA, you need to register on the website and call a courier in your personal account who will bring you a box with a plastic test tube, a barcode and an agreement on the use of your biomaterials. Before you fill the test tube with saliva (it takes a long time to spit), you can’t eat, drink and kiss for half an hour. After filling, the test tube is closed with a special stopper, which contains a liquid preservative, and the courier is called again. In addition, in your personal account you will be asked to fill out a fairly detailed questionnaire about the diseases of your relatives and your lifestyle (what you eat, how often you play sports, what you were sick with and what operations you did). They promise to send the test results in two weeks, but in my case a whole month has passed. As Sergei Musienko, the founder of Atlas, later told me, they conduct DNA research at the laboratory of the Research Institute of Physical and Chemical Medicine in Moscow.

The report itself looks like an electronic page with a rubricator: health, nutrition, sports, origins, personal qualities and recommendations.

The most serious and reliable heading is health: in it, the connection of certain types of genes with a possible disease is confirmed by scientific studies in which more than a thousand people took part. Here, the risks of developing diseases are grouped in percentages and compared with the average risk for the population, hereditary diseases are displayed, as well as the so-called pharmacogenetics, individual sensitivity to drugs (allergic reactions, side effects).

The Village correspondent tested negative for a genetic variant often found in curly-haired people

The highest risks for me, according to the test, are melanoma (0.18% with an average risk of 0.06%), systemic scleroderma (0.05% with an average of 0.03%), type 1 diabetes mellitus (0.45% with average 0.13%), aneurysm of cerebral vessels (2.63% with average 1.8%), systemic lupus erythematosus (risk 0.08% with average risk 0.05%), endometriosis (1.06% with average risk 0.81%), arterial hypertension (42.82% with an average risk of 40.8%). Well, and so on. In addition, the test revealed that I am a healthy carrier of a gene variant associated with periodic illness. My sensitivity to drugs turned out to be completely average, unremarkable, so the test did not reveal any special side effects or allergic reactions.

In the “Nutrition” section, I was recommended what all healthy lifestyle magazines recommend to their readers - a balanced diet and for some reason no more than 998 kilocalories per day (against the norm for an adult who does not play sports, 1,200). They did not recommend eating sweet and fatty foods, drinking strong alcohol, eating potatoes or eating rice, they banned sweet and fried foods. In general, everything that could be advised to any Russian over 18 years old. I was suspected of being lactose intolerant and banned dairy products, although I never had any problems with milk. Despite this, in the "Recommendations" section, I was advised to eat "more dairy products every day" (the developers later said that this is a bug), because milk "reduces the risk of developing diabetes", which I have increased. If you drink it instead of sweet soda, then it probably reduces. But now progressive humanity is already thinking about how much milk is generally necessary for an adult - the connection between milk consumption and strong bones and the replenishment of vitamin D, which was discussed earlier, has not been found.

In the "Sports" section, I was called a "sprinter" and advised strength training, so handball, rugby and swimming were recommended, and running, basketball, equestrianism and winter sports were banned. To my surprised question: “Why was running banned, which is possible for almost everyone?” - Geneticist Irina Zhigulina, with whom we later spoke, replied that we were talking about professional sports. They don't think I'll be a professional runner.

In the Origins section, I had an interactive infographic about how my maternal ancestors left East Africa 150,000-180,000 years ago and moved into Northern Europe. I do not have a Y chromosome, so what happened to the paternal line is completely incomprehensible. My hopes of finding successful relatives never materialized - the slider stopped at the mark "500 years ago" and gave the result that 50.9% of my DNA is from the inhabitants of Northern Europe. It is a pity that this is not at all what the buyers of the 23andMe test get, for example, who are given access to a social network where they can find their relatives. And I really wanted to live such a story as Stacey and Greta, who found out that they are sisters, thanks to 23andMe!

I was most surprised by the information under the heading "Personal Qualities". Here I learned that I had a reduced risk of developing nicotine addiction, a predisposition to absolute pitch, no risk of early menopause, and a tendency to avoid harm. The creators refer to this section as “entertainment genetics” because the data in it is built on the basis of experiments with a small sample of subjects (less than 500). But they did not entertain me at all, but upset me. First, it turned out that I do not have a predisposition to curly hair: “you have not identified a genetic variant that is often found in curly people,” although I am curlyer than many astrakhan fur coats. And secondly, I “have not identified a gene variant found in most creative people.” Third, I am an introvert.

Box with genetic test
Inside is an agreement to use your biomaterials
As well as a test tube that needs to be filled with saliva

The test results end with recommendations to consult with a general practitioner (for the risk of systemic lupus erythematosus), with an endocrinologist (for diabetes mellitus) and with a dermatologist (scleroderma, melanoma), as well as annually take a blood test, do a mammogram, from the age of 40 - regularly ECG . They also recommended drinking coffee and milk, vitamins, exercising regularly and rarely sunbathing.

Irina Zhigulina, Atlas geneticist, who called me after receiving the results, reassured me, explaining that the genetic risk is only a predisposition, and not a future diagnosis at all, and lifestyle can correct this risk. According to her, one should carefully look at relatives - at what age and how they started to get sick.

Irina explained that the high risk of most diseases that I may be genetically prone to (hypertriglyceridemia, coronary disease, diabetes) is reduced by a healthy lifestyle and stress reduction. And the disease, the passive carrier of which I can be, will never manifest itself, but you should not choose men with the same mutation as fathers for the unborn child. “But in general,” Irina concluded, “you are an ideal woman. And curly hair is a complex trait, and it depends on more than just one gene.”

After I sent questions through the Atlas press service about the lack of a genetic propensity for curly hair and creativity, the results of my test in my personal account changed. Now, about curly, it was written that my hair “prone to straightness by 23%, wavy by 48% and curly by 29%”, and data on the lack of creativity disappeared altogether.

Sergey Musienko, CEO of Atlas, explained that a personal account is a living organism that changes depending on the appearance of new research, but they have not yet implemented a system for notifying customers about this. I'm one of their first clients, so they listened to my feedback, looked again at the study, which concluded that genetics and creativity were linked based on too small a sample (58 people), and decided to remove this attribute altogether until new data appeared on larger sample. The data on my curlyness is determined by several positions of the gene, so there is no one-to-one correspondence between the gene and the curly hair. Previously, they used one position of this trait, and now they use three - and this is how the change in my results happened.

Since I am neither a doctor nor a geneticist, I asked Konstantin Severinov, head of the laboratory for regulation of prokaryotic element gene expression at the Institute of Molecular Genetics of the Russian Academy of Sciences, Konstantin Severinov, head of the laboratory of molecular genetics of microorganisms at the Institute of Gene Biology of the Russian Academy of Sciences, and my mother, a general practitioner, to comment on the test results.

KONSTANTIN SEVERINOV

Doctor of Biological Sciences, Professor at Rutgers University (USA), Professor at the Skolkovo Institute of Science and Technology (Skoltech)

With the exception of rather rare markers for severe genetic diseases (such as cystic fibrosis), the usefulness of such predictions tends to be zero. This certainly applies to IQ markers and sports and diet advice. The problem is that the likelihood of genetic risks for diseases is so small that most people will never experience these diseases. Even an increased likelihood (whatever that means) of what is already quite small has no real meaning and is not a serious probability of developing the disease.

No one can say what exactly the phrase “the risk of developing disease X is five times increased” means for a particular person.

irina sheveleva

therapist and mother of the subject

Diabetes mellitus 0.45% - this means that it is not there, a serious risk is 30-40%. SLE (systemic lupus erythematosus) is such a rare disease that in all my years of practice I have only met patients with proven lupus erythematosus three times. In my opinion, Dr. House, unlike me, in six seasons never found a single such patient. Scleroderma is an exotic, systemic disease that affects the connective tissue, psoriasis is mainly suffered by alcoholics, Sasha has already passed type 1 diabetes, this is childhood diabetes, which manifests itself at an early age. Type 2 diabetes can only occur if a person is seriously gaining weight. Hypertension - also somehow looks suspicious, because in our family all are hypotensive. Melanoma is a malignant skin tumor that affects people with very high incomes more often because they travel from one resort to another during the year. You still have to live up to coronary disease: up to the age of 70, women are protected from it by hormones. Ulcerative colitis can develop if you eat once a week and the immune system changes so that instead of neutralizing agents that come from outside, it begins to damage the tissues of its own body. If ulcerative colitis manifests itself, then up to 30 years. This is a rare disease, we have one such patient in 30,000 of the population we serve. Armenians, Jews suffer from periodic illness, I saw one Arab. It is also called the disease of the Mediterranean. This is such a rare systemic disease, once you see such a patient and then you will talk all your life. Sasha was recommended a "balanced diet". Well, who would argue! We all need to balance our diet. Only, consuming 998 kilocalories per day, she will not last long. 1,200 kilocalories barely cover the expenses of a person leading a sedentary lifestyle. An endocrinologist would have killed on the spot for such a recommendation. The results of the test revealed a tendency to lactose intolerance. But that means you drink pasteurized milk from a bottle and 20 minutes later you have an upset stomach. But this is not true. If this test was done correctly, then it was misinterpreted, because there is no binding to a specific person and very general recommendations.

sergey musienko

General Director of the biomedical holding "Atlas"

A genetic test analyzes DNA and characterizes in several ways: a person's susceptibility to common diseases, hereditary disease carrier status, drug response, and ancestry data. The results differ in the degree of scientific validity: some data are more studied, some require additional research. In your personal account, screening results are divided by reliability - from one star (data from less than a thousand people were studied) to four stars (studies were conducted involving more than a thousand people and recommendations for disease prevention were developed). 29 out of 114 common diseases (such as type 2 diabetes) and all hereditary and drug reactions have the maximum confidence status. In the personal account, the results of each direction are supported by a link to scientific articles. The Atlas screening test evaluates about 550 thousand gene variants, which makes it possible to determine a person's predisposition to 114 common diseases, the carrier status of 155 hereditary diseases and the response to 66 drugs.

All tests are carried out in a Moscow laboratory based at the Research Institute of Physical and Chemical Medicine. Biological material is collected in a test tube with a special preservative solution, DNA molecules are isolated from saliva in the laboratory, which are then copied a huge number of times. The obtained millions of copies of DNA are cut into small pieces, processed and placed on a special DNA chip, which is placed in the scanner. On each of the 12 cells of the chip (one cell per test sample), short sections of the synthesized DNA are applied, with which the DNA of the test sample interacts or does not interact. The device determines a successful reaction with the test sample and outputs information about point changes in the test genome in the format of a huge picture. The data is then converted into a table with 550,000 rows for each sample.

Then the most interesting thing happens - the interpretation of the data. This part of the analysis is our own development and allows us to compare the results obtained with the results of thousands of the latest scientific articles and clinical guidelines for disease prevention. You will see the results of this algorithm in your personal account in the form of infographics and lists of studied features. On average, the analysis of test results takes two weeks. The technology of genotyping using DNA chips that we use is young, but has already proved itself in hundreds of scientific projects around the world. This solution is also used by 23andMe for its analysis.

However, we managed to make this technology available to Russian customers (it is more expensive for other Russian companies). An important difference of our company is a close connection with the doctors of our own medical center. After passing the analysis, the user can undergo an online consultation with a geneticist who will help interpret the results - it is included free of charge in each test. Also, a person has the opportunity to make an appointment with a doctor, show test data and develop an individual examination plan. At the same time, we do not impose the services of our medical center - it can undergo further diagnostics at any other clinic. Before taking the analysis, the user fills out a questionnaire about the features of his lifestyle, which subsequently becomes part of his electronic medical record, which combines the data of the medical history and the results of the study. Access to it is available to both the doctor and the patient.

Photos: Ivan Anisimov

Cancer kills millions of people every year. Among the causes of death, cancer ranks second after cardiovascular diseases, and in terms of the fear that accompanies it, it is definitely the first. This situation has developed because of the perception that cancer is difficult to diagnose and almost impossible to prevent.

However, every tenth case of cancer is a manifestation of mutations inherent in our genes from birth. Modern science allows them to catch and significantly reduce the risk of disease.

Oncology experts talk about what cancer is, how much genetics influences us, who should get genetic testing as a preventative measure, and how it can help if cancer is already detected.

Ilya Fomintsev

Executive Director of the Foundation for the Prevention of Cancer "Not in vain"

Cancer is essentially a genetic disease. Mutations that cause cancer are either inherited, and then they are in all cells of the body, or appear in some tissue or a specific cell. A person can inherit from their parents a specific mutation in a gene that protects against cancer, or a mutation that itself can lead to cancer.

Non-hereditary mutations occur in initially healthy cells. They occur under the influence of external carcinogenic factors, such as smoking or ultraviolet radiation. Basically, cancer develops in people in adulthood: the process of occurrence and accumulation of mutations can take more than a dozen years. People go through this path much faster if they inherited a breakdown already at birth. Therefore, with tumor syndromes, cancer occurs at a much younger age.

This spring, a wonderful article came out - about random errors that occur during the duplication of DNA molecules and are the main source of oncogenic mutations. In cancers such as prostate cancer, their contribution can be as high as 95%.

Most often, non-hereditary mutations are the cause of cancer: when a person has not inherited any genetic damage, but during life, errors accumulate in the cells, which sooner or later lead to the appearance of a tumor. Further accumulation of these breakdowns already inside the tumor can make it more malignant or lead to the emergence of new properties.

Despite the fact that in most cases, oncological diseases arise due to random mutations, one must take the hereditary factor very seriously. If a person knows about the inherited mutations that he has, he will be able to prevent the development of a particular disease, the risk of which he has a very high risk of developing.

There are tumors with a pronounced hereditary factor. These are, for example, breast cancer and ovarian cancer. Up to 10% of these cancers are associated with mutations in the BRCA1 and BRCA2 genes. The most common type of cancer among our male population - lung cancer - is mostly caused by external factors, and more specifically, by smoking. But if we assume that external causes have disappeared, then the role of heredity would become approximately the same as in breast cancer. That is, in relative terms for lung cancer, hereditary mutations are seen rather weakly, but in absolute numbers it is still quite significant.

In addition, the hereditary component quite significantly manifests itself in cancer of the stomach and pancreas, colorectal cancer, and brain tumors.

Anton Tikhonov

scientific director of the biotechnology company yRisk

Most cancers are caused by a combination of random events at the cellular level and external factors. However, in 5-10% of cases, heredity plays a predetermining role in the occurrence of cancer.

Let's imagine that one of the oncogenic mutations appeared in a germ cell, which was lucky to become a human. Each of the approximately 40 trillion cells of this person (as well as his descendants) will contain a mutation. Therefore, each cell will need to accumulate fewer mutations in order to become cancerous, and the risk of developing a certain type of cancer in a mutation carrier will be significantly higher.

An increased risk of developing cancer is passed from generation to generation along with a mutation and is called hereditary tumor syndrome. Tumor syndromes are quite common - in 2-4% of people, and cause 5-10% of cancer cases.

Thanks to Angelina Jolie, hereditary breast and ovarian cancer, which is caused by mutations in the BRCA1 and BRCA2 genes, has become the most famous tumor syndrome. In women with this syndrome, the risk of developing breast cancer is 45-87%, while the average probability of this disease is much lower - 5.6%. The likelihood of developing cancer in other organs also increases: the ovaries (from 1 to 35%), the pancreas, and in men also the prostate gland.

Almost any cancer has hereditary forms. Tumor syndromes are known to cause cancer of the stomach, intestines, brain, skin, thyroid gland, uterus, and other less common types of tumors.

Knowing that you or your relatives have a hereditary tumor syndrome can be very helpful in reducing the risk of developing cancer, diagnosing it at an early stage, and treating the disease more effectively.

Carrier syndrome can be determined using a genetic test, and the fact that you should take the test will be indicated by the following features of family history.

Several cases of the same type of cancer in the family;

Diseases at an early age for this indication (for most indications - before 50 years);

A single case of a specific type of cancer (eg, ovarian cancer);

Cancer in each of the paired organs;

More than one type of cancer in a relative.

If any of the above apply to your family, you should consult a geneticist who will determine if there is a medical indication for a genetic test. Carriers of hereditary tumor syndromes should undergo thorough cancer screening in order to detect cancer at an early stage. And in some cases, the risk of developing cancer can be significantly reduced with the help of preventive surgery and drug prophylaxis.

Despite the fact that hereditary tumor syndromes are very common, Western national health systems have not yet introduced genetic testing for mutation carriers into widespread practice. Testing is recommended only if there is a specific family history that points to a specific syndrome, and only if the person is known to benefit from testing.

Unfortunately, such a conservative approach misses many carriers of the syndromes: too few people and doctors suspect the existence of hereditary forms of cancer; high risk of the disease is not always manifested in family history; many patients do not know about the diseases of their relatives, even when there is someone to ask.

All this is a manifestation of modern medical ethics, which says that a person should know only what will bring him more harm than good.

Moreover, doctors leave the right to judge what is benefit, what is harm, and how they relate to each other, exclusively to themselves. Medical knowledge is the same interference in worldly life, like pills and operations, and therefore the measure of knowledge should be determined by professionals in bright clothes, otherwise, no matter how something happens.

I, like my colleagues, believe that the right to know about one's own health belongs to people, not to the medical community. We are doing a genetic test for hereditary tumor syndromes so that those who want to know about their risks of developing cancer can exercise this right and take responsibility for their own lives and health.

Vladislav Mileiko

Director of Atlas Oncology Diagnostics

As cancer develops, cells change and lose their original genetic "look" inherited from their parents. Therefore, in order to use the molecular features of cancer for treatment, it is not enough to study only hereditary mutations. Molecular testing of samples obtained from a biopsy or surgery should be performed to find out the weak points of the tumor.

Genome instability allows the tumor to accumulate genetic disorders that may be beneficial to the tumor itself. These include mutations in oncogenes - genes that regulate cell division. Such mutations can greatly increase the activity of proteins, make them insensitive to inhibitory signals, or cause increased production of enzymes. This leads to uncontrolled cell division, and subsequently to metastasis.

what is targeted therapy

Some mutations have known effects: we know exactly how they change the structure of proteins. This makes it possible to develop drug molecules that will act only on tumor cells, and at the same time will not destroy normal cells of the body. Such drugs are called targeted. For modern targeted therapy to work, it is necessary to know what mutations are in the tumor before prescribing treatment.

These mutations can vary even within the same type of cancer. (nosology) in different patients, and even in the same patient's tumor. Therefore, for some drugs, molecular genetic testing is recommended in the instructions for the drug.

Determination of tumor molecular changes (molecular profiling) is an important link in the clinical decision chain, and its importance will only grow with time.

To date, more than 30,000 studies of antitumor therapy are being conducted in the world. According to various sources, up to half of them use molecular biomarkers to enroll patients in a study or for monitoring during treatment.

But what will molecular profiling give the patient? Where is its place in clinical practice today? Although testing is mandatory for a number of drugs, this is just the tip of the iceberg of current molecular testing capabilities. Research results confirm the impact of various mutations on the effectiveness of drugs, and some of them can be found in the recommendations of international clinical communities.

However, at least 50 additional genes and biomarkers are known, the analysis of which may be useful in the choice of drug therapy (Chakravarty et al., JCO PO 2017). Their determination requires the use of modern methods of genetic analysis, such as high throughput sequencing(NGS). Sequencing makes it possible to detect not only common mutations, but also to “read” the complete sequence of clinically significant genes. This allows you to identify all possible genetic changes.

At the stage of analysis of the results, special bioinformatic methods are used that help to identify deviations from the normal genome, even if an important change occurs in a small percentage of cells. The interpretation of the result obtained should be based on the principles of evidence-based medicine, since the expected biological effect is not always confirmed in clinical studies.

Due to the complexity of the process of conducting research and interpreting the results, molecular profiling has not yet become the "gold standard" in clinical oncology. However, there are situations in which this analysis can significantly influence the choice of treatment.

Exhausted possibilities of standard therapy

Unfortunately, even with the right treatment, the disease can progress, and there is not always a choice of alternative therapy within the standards for this cancer. In this case, molecular profiling can reveal "targets" for experimental therapies, including those in clinical trials (eg TAPUR).

the range of potentially significant mutations is wide

Some cancers, such as non-small cell lung cancer or melanoma, are known to have multiple genetic alterations, many of which could be targets for targeted therapy. In this case, molecular profiling can not only expand the choice of possible treatment options, but also help prioritize the choice of drugs.

Rare types of tumors or tumors with an initially poor prognosis

Molecular research in such cases helps to identify a more complete range of possible treatment options at an early stage.

Molecular profiling and treatment personalization require the collaboration of specialists from several fields: molecular biology, bioinformatics and clinical oncology. Therefore, such a study, as a rule, is more expensive than conventional laboratory tests, and only a specialist can determine its value in each case.

Cancer is caused by errors in DNA, and a new study has found that in most cases of cancer, these errors are completely random. They are not caused by hereditary predisposition or environmental factors, but the result of random failures.

The study says that mistakes or mutations contribute to the development of cancer, because even a tiny mistake in DNA can cause cells to multiply out of control.

Scientists believe that these mutations are caused mainly by two things: either the mutation has a genetic basis, or it is caused by external factors that can damage DNA, such as cigarette smoke or ultraviolet radiation.

But the third reason lies in random errors. A new scientific report published in the journal Science claims that this factor actually accounts for two-thirds of these mutations. When a cell divides, it copies its DNA. So each new cell will have its own version of the genetic material. But every time such a copy occurs, there is an opportunity for subsequent error. And in some cases, these mistakes can lead to cancer.

Research scientists

"Research has shown that cancer will grow in the body regardless of environmental exposure," said senior researcher Dr. Bert Vogelstein, pathologist at the Sydney Kimmel Comprehensive Cancer Center at Johns Hopkins University.

In a new scientific study, scientists set out to calculate what percentage of cancer cases were caused by hereditary factors, environment and random errors. The scientists developed a mathematical model that included data from cancer registries around the world, as well as DNA sequencing indicators.

Random error

The study states that about 66% of cancers were caused by random errors, 29% of cancers were triggered by environmental factors or the wrong lifestyle of people. And only in 5% of cases of development of cancerous neoplasms, inherited mutations served as a trigger.

The researchers note that this assessment is somewhat different from the views of other scientists who have studied cancer. For example, scientists in the UK claim that 42% of cancer could be prevented by changing the lifestyle of patients.

The scientific paper claims that some types of cancer, such as brain and prostate tumors, are almost entirely due to random errors. The scientists found that random errors caused more than 95% of the disease cases that were examined in the scientific study.

Graphical representation of the study

In one of the graphic images, scientists used red coloration to indicate the percentage of cancer in women. Diseases attributed to inherited mutations were located on the left side. Those related to random errors are in the center, and those related to environmental factors are on the right side.

For each organ, the color was a percentage that relates to a particular factor, from white (0%) to red (100%).

Cancers have been identified as:

• B - brain.
• Bl - bladder.
• Br - chest.
• C - cervical.
• CR - colorectal.
• E - esophagus.
• HN - head and neck.
• K - kidneys.
• Lee is the liver.
• Lk - leukemia.
• Lou - lungs.
• M - melanoma.
• NHL - non-Hodgkin's lymphoma.
• O - ovarian.
• P - pancreas.
• S - stomach.
• Th - thyroid gland.
• U - uterus.

Influence of external factors

According to the results of the work of scientists, for some cancers, environmental factors play a large role. For example, negative environmental influences, primarily smoking, caused 65% of all cases of lung cancer. The researchers found that only 35% of lung cancers were caused by random errors.

"A single mutation in a cell is unlikely to cause cancer," Vogelstein said in a scientific paper prepared by Johns Hopkins. "Rather, the more mutations there are, the more likely the cell is to become cancerous," he said.

Combination of DNA errors and external factors

"Thus, mutations from random errors are enough to cause cancer that develops on its own in some cases," Vogelstein says. But, according to the scientist, in other cases, a combination of random errors, as well as errors caused by environmental factors, ultimately leads to cell cancer. For example, skin cells have a baseline mutation rate due to random errors and exposure to ultraviolet light. "Things like that could add even more mutations leading to cancer," Vogelstein says.

Three causes of mutations at the cellular level

Christian Tomasetti, Associate Professor of Biostatistics at Johns Hopkins, mentioned three causes of mutations using the example of keyboard typos. Some of these typographical errors may be the result of typist fatigue or distraction. They can be considered as environmental factors. "And if the keyboard that the typist uses is missing a key, then it's a hereditary factor," Tomasitti says in his report.

“But even in an ideal environment, when the typist is well rested and using a perfectly functioning keyboard, there will still be typos,” the scientist says. And this is a random error.

What does research for prevention mean?

There are specific cancer prevention strategies that are caused by environmental or genetic causes. To help reduce the risk of contracting lung cancer, a smoker can stop smoking, and a woman who has been diagnosed with breast cancer can have a prophylactic mastectomy.

According to the researchers, these primary prevention strategies are considered the best way to reduce cancer death rates. The authors note that such primary prevention is not possible in cancers caused by random mutations, but secondary prevention can still help keep patients alive.

According to the study, secondary prevention refers to the early detection of cancer. "We need to focus more on early detection because the process is not an avoidable mutation," Tomasitti says in the report.

Malignant tumors are the second most common cause of death in the world. Often patients turn to doctors already in the later stages of the disease, when even surgical interventions no longer give results. Therefore, doctors focus on the timely establishment of inheritance factors, the so-called predisposition to cancer. Identification of risk factors and grouping patients into specific groups for detailed observation should play an important role in achieving greater success and effectiveness of treatment. These steps will allow you to find a tumor at the beginning of formation and help to suppress the pathological process.

After a series of studies, scientists have identified factors that significantly increase the risk of developing cancerous tumors. These factors are divided into the following groups.

• chemical carcinogens - increase the risk of disease in people who are constantly in contact with substances harmful to health;
• physical carcinogens - the negative impact of ultraviolet radiation, exposure during research involving x-rays and radioisotopes, living in regions with a high content of radioactive substances;
• biological carcinogens - viruses that change the genetic structure of the cell. The group also includes natural hormones that can develop carcinomas of a hormone-dependent organ. High estrogen, for example, increases the risk of breast cancer, and high testosterone increases the risk of malignant type prostate carcinomas;
• lifestyle - the most common factor in oncopathology - smoking - increases the risk of cancer of the respiratory organs, and tumors of the stomach or cervix.

A separate and important, from the point of view of medical research, factor that is currently being given special attention is hereditary predisposition.

Faced with a cancerous disease, the same question begins to arise in the brain of many: can the disease be inherited or is there no cause for concern? You should not relax, since the inherited predisposition plays a huge role in the development of diseases. Genes - structural sections with nucleic acids functionally transmit the heredity of living organisms. The necessary information is read from these sections for the further development of the carrier. Some genes are responsible for internal organs, others take control of such indicators as hair color, eye color, and so on. In the structure of one cell, there are more than thirty thousand genes that prescribe the code for protein synthesis.

Genes are part of chromosomes. At conception, the gestating fetus receives half of the chromosome set from each parent. In addition to the “correct” genes, mutated ones may also be transmitted, which, in turn, will lead to distortion of gene information and incorrect protein synthesis - all this can have a dangerous effect, especially if suppressor genes and oncogenes are subjected to changes . Suppressors protect DNA from damage, oncogenes are responsible for cell division.

Mutant genes react completely unpredictably to the environment. This reaction often leads to the appearance of oncological formations.

Modern medicine does not question the existence of a predisposition to cancer. According to some reports, 5-7% of cancer cases are caused by a genetic factor. Among doctors there is even a term "cancer families" - families in which tumors were diagnosed in at least 40% of relatives by blood. At the moment, genetic scientists know almost all the genes responsible for the development of carcinomas. Unfortunately, molecular genetics is an expensive branch of science, especially in terms of laboratory research, so it is not yet possible to widely use it. The main work of geneticists at the present time is the study of pedigrees. It is extremely important after their analysis to receive effective and clear recommendations from a specialist regarding the patient's lifestyle, tips that help prevent the occurrence of formations. With different forms of cancer and taking into account the age of patients, the intervals between examinations to determine the right advice can vary from longer to shorter.

• inheritance of genes responsible for a specific form of cancer;
• transfer of genes that increase the risk of disease;
• the occurrence of a disease when several traits are inherited at the same time.

Today, science identifies several dozen different types of cancer that have a hereditary factor. Most often, formations are found in the mammary gland, lungs, ovaries, large intestine or stomach, as well as acute leukemia and malignant melanoma.

The high incidence rate motivates oncologists to constantly develop methods for early diagnosis and effective treatment of cancer, including those that have arisen due to a genetic predisposition. When assessing the degree of heritability of the risks of developing carcinoma, it is important to carefully consider the patient's family history.

The following features of the medical pedigree should be emphasized:

1. Oncological tumors in relatives up to fifty years old.
2. The development of the same type of oncopathology in different generations within the same pedigree.
3. Relapses in the same relatives.

Discuss the results of family disease testing with a genetic oncologist. The consultation will more accurately determine whether a predisposition and risk analysis is necessary.

Before carrying out a genetic analysis, carefully weigh the pros and cons of this procedure for yourself. On the one hand, the study can determine the risks of developing tumors, on the other hand, it will make you fear for no real reason, as well as inadequately and with an “inflection” attitude to health and suffer from cancerophobia.

The level of inherited disposition is determined by the molecular genetic method of research. It allows you to identify a number of mutations in oncogenes and suppressor genes that are responsible for an increased risk of developing oncopathologies. If cancer risks are identified, continuous follow-up by oncologists who can diagnose the tumor at an early stage is recommended.

Genetic analysis for cancer is a modern method for diagnosing and preventing susceptibility to cancer. Are such studies reliable and should everyone pass it? - questions that concern both scientists and potential patients. Given that in Russia, genetic analysis, for example, for breast and ovarian cancer will cost about 4,500 rubles, it becomes clear that many would like to first understand whether it is really worth including this study in articles of personal and family expenses.

Indications for the study

Genetic analysis, which reveals cancerous heredity, is able to determine the risks of the following pathologies:

• mammary gland;
• respiratory organs;
• genital organs (glands);
• prostate;
• intestines.

Another indication is the suspicion of the presence of other diseases in the patient. Such non-oncological diseases in the future increase the possibility of cancer of various organs.

In this case, it is necessary to conduct a diagnosis and find out if there are certain congenital syndromes that sometimes precede cancerous tumors of the respiratory or digestive system.

What does a genetic test show?

Scientists have found that changing some genes most often leads to oncological tumors. Every day, cells with malignant characteristics proliferate in the human body, but our immune system, supported by special genetic structures, copes with them.

In case of violations in the structure of DNA, the work of “protective” genes is disrupted, thereby increasing the oncological risk. Such “breakdowns” in the genes are inherited.

An example is the well-known case of Angelina Jolie: one of the relatives in the family was diagnosed with breast cancer, so the famous actress underwent a genetic test, and she, in turn, revealed mutations in the genes. Alas, the only thing doctors could do in this case was to remove the breasts and ovaries, that is, they eliminated the organs in which the mutated genes progress. However, do not forget that each case is individual and the methods of prevention and treatment may differ significantly from the described example.

Can genetic analysis be trusted?

The dysfunction in the BRCA1 and BRCA2 genes, which, during normal operation, prevent the occurrence of breast and ovarian cancer, has been most studied in detail. But as time passed, doctors noticed that the time and money spent on genetic development did not significantly reduce the mortality rate among women. Therefore, it is not worth using genetic analysis as a screening diagnostic method for each individual person, but such an analysis is quite suitable for determining risk groups.

Confidence in the results obtained is an individual choice. With a negative result, it is probably not necessary to urgently carry out a preventive complete removal of the organ. However, if violations in the genes are still detected, begin to carefully monitor your health and conduct periodic diagnostics.

In percentage terms, it is difficult to determine indicators for genetic diagnosis, since for this it is necessary to analyze a large number of cases with both positive and negative results. Nevertheless, it can already be stated for sure today that such an analysis is highly sensitive, and its results should be relied upon.

The obtained indicators after testing will not answer 100% of the patient's question whether he will ever get cancer or not. It is difficult to draw conclusions from a negative result: it only shows that the risk of developing cancer is not higher than the average statistical indicators of the population. But a positive answer gives more accurate and detailed information to both the doctor and the subject.

For the accuracy of test results, do not forget about the rules for preparing for analysis.

• exclude alcohol seven days before the diagnosis;
• stop smoking for three to five days before donating blood;
• the last meal - ten hours before the examination.

Who should get tested

Genetic testing does not have precise indications for passing the type of specific age or general physical condition of the patient. Everyone can pass the test, especially if passing the test will not only help you gain some certainty, but also bring peace of mind.

However, there are several examples in which the examination is still worth it:

• if a tumor in the mammary gland is found in the mother of a young girl, one should not wait several years to test this girl for a predisposition. It is better to immediately warn yourself and other younger blood relatives. It is recommended to be examined to confirm or exclude a genetic mutation and the risk of developing cancer;
• men over the age of 50 who are diagnosed with serious acute or chronic prostate problems should be tested and assessed for the risk of prostate tumor growth;
• in general, any malignant tumors in relatives are already a sufficient reason for the analysis, but entrust the appointment of an examination to a geneticist who is able to evaluate the results.

Remember, the age of the subject during the test does not matter at all. Disruption of the genes is programmed at birth. Thus, if at 25 the results showed that the genes are in perfect order, then there is no point in undergoing the same test in ten, fifteen, twenty years.

General Cancer Prevention

The appearance of tumors, even with pronounced heredity, can be partially prevented.

• give up bad habits that cause addiction (alcohol, smoking);
• eat healthy food by increasing the intake of vegetables, fruits and reducing animal fats in the diet;
• maintain weight within normal limits;
• provide the body with constant physical exercise;
• protect the skin from direct ultraviolet radiation;
• to affix the necessary vaccinations;
• undergo preventive diagnostics;
• seek medical assistance in case of malfunctions in the body immediately.

Care and scrupulous attitude to your own body is the key to reducing the chances of cancer. Trying to prevent a disease is always easier than trying to treat it.

Even with 100% detection of the possibility of cancer, preventive methods are limited. A simple observation by an oncologist without a detailed examination, for example, cannot be regarded as effective prevention, but rather as a passive expectation of the onset of the disease. At the same time, cardinal interventions such as preventive removal of the mammary glands are far from always justified and make sense.

Unfortunately, today, apart from seeing a doctor and passing tests, oncology does not provide reliable methods and means of prevention.

1. To study the medical history of the family, and in several generations.
2. Be observed periodically by an oncologist, especially if blood relatives were sick.
3. Undergo genetic analysis if there is reason to worry about the results based on the studied pedigree.
4. Use prevention and general health advice to reduce risk factors, regardless of test results.

The main thing to remember is that predisposition to a disease is not the disease itself. Keep a positive attitude, devote more time to your own health, trust the care of specialists in the field of oncology and genetics.