Analysis to identify genetic predisposition to cancer. Breast and ovarian cancer - basic. What data might be useful?

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 suggests that errors or mutations contribute to the development of cancer because even a tiny DNA error can cause cells to multiply uncontrollably.

Scientists believe that these mutations are caused primarily 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 copying occurs, the possibility of subsequent error is created. And in some cases, these errors can lead to cancer.

Research by scientists

"Research has shown that cancer will grow in the body regardless of environmental exposure," said senior scientist Dr. Bert Vogelstein, a pathologist at the Sidney 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, the 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 accidental errors, 29% of cancers were triggered by environmental factors or poor lifestyle choices of people. And only 5% of cases of cancer development were triggered by inherited mutations.

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

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

Graphic representation of the study

In one graphic, the scientists used red coloring to indicate the percentage of cancerous lesions 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, color represented the percentage that was assigned to a specific factor, ranging 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 - liver.
• Lk - leukemia.
• Lu - 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 scientists' work, environmental factors play an important role for some cancers. For example, negative environmental influences, primarily smoking, caused 65% of all cases of lung cancer. The researchers found that only 35% of lung cancer cases were caused by random errors.

“A single mutation in a cell is unlikely to cause cancer,” Vogelstein said in a scientific report prepared by Johns Hopkins. “Rather, the more mutations there are, the more likely the cell is to become malignant,” the specialist said.

Combination of DNA errors and external factors

“So mutations from random errors are enough to cause cancer, which develops on its own in some cases,” says Vogelstein. 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 base level of mutation due to random errors and exposure to ultraviolet light. “Such factors can add even more mutations that lead to cancer,” says Vogelstein.

Three causes of mutations at the cellular level

Christian Tomasetti, assistant professor of biostatistics at Johns Hopkins, mentioned three causes of mutation using the example of typos that occur when using a keyboard. Some of these typos may be the result of typist fatigue or distraction. They can be considered as environmental factors. “And if the keyboard the typist uses is missing a key, then this is a hereditary factor,” Tomasitti said in his report.

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

What does research mean for prevention?

There are specific strategies to prevent cancer caused by environmental or genetic factors. To help reduce the risk of getting lung cancer, a smoker can quit smoking, and a woman who has been diagnosed with breast cancer can have a prophylactic mastectomy.

These primary prevention strategies are considered the best way to reduce cancer mortality rates, the researchers report. The authors note that such primary prevention is not possible for cancers caused by random mutations, but secondary prevention can still help save patients' lives.

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 said in the report.

Head of
"Oncogenetics"

Zhusina
Yulia Gennadievna

Graduated from the Pediatric Faculty of Voronezh State Medical University. N.N. Burdenko in 2014.

2015 - internship in therapy at the Department of Faculty Therapy of VSMU named after. N.N. Burdenko.

2015 - certification course in the specialty “Hematology” at the Hematology Research Center in Moscow.

2015-2016 – therapist at VGKBSMP No. 1.

2016 - the topic of the dissertation for the degree of Candidate of Medical Sciences “study of the clinical course of the disease and prognosis in patients with chronic obstructive pulmonary disease with anemic syndrome” was approved. Co-author of more than 10 published works. Participant of scientific and practical conferences on genetics and oncology.

2017 - advanced training course on the topic: “interpretation of the results of genetic studies in patients with hereditary diseases.”

Since 2017, residency in the specialty “Genetics” on the basis of RMANPO.

Head of
"Genetics"

Kanivets
Ilya Vyacheslavovich

Kanivets Ilya Vyacheslavovich, geneticist, candidate of medical sciences, head of the genetics department of the medical genetic center Genomed. Assistant at the Department of Medical Genetics of the Russian Medical Academy of Continuing Professional Education.

He graduated from the Faculty of Medicine of the Moscow State Medical and Dental University in 2009, and in 2011 – a residency in the specialty “Genetics” at the Department of Medical Genetics of the same university. In 2017, he defended his dissertation for the scientific degree of Candidate of Medical Sciences on the topic: Molecular diagnostics of copy number variations of DNA sections (CNVs) in children with congenital malformations, phenotypic anomalies and/or mental retardation using high-density SNP oligonucleotide microarrays.”

From 2011-2017 he worked as a geneticist at the Children's Clinical Hospital named after. N.F. Filatov, scientific advisory department of the Federal State Budgetary Institution “Medical Genetic Research Center”. From 2014 to the present, he has been heading the genetics department of the Genomed Medical Center.

Main areas of activity: diagnosis and management of patients with hereditary diseases and congenital malformations, epilepsy, medical and genetic counseling of families in which a child was born with hereditary pathology or developmental defects, prenatal diagnosis. During the consultation, clinical data and genealogy are analyzed to determine the clinical hypothesis and the necessary amount of genetic testing. Based on the results of the survey, the data are interpreted and the information received is explained to the consultants.

He is one of the founders of the “School of Genetics” project. Regularly gives presentations at conferences. Gives lectures for geneticists, neurologists and obstetricians-gynecologists, as well as for parents of patients with hereditary diseases. He is the author and co-author of more than 20 articles and reviews in Russian and foreign journals.

Area of ​​professional interests is the implementation of modern genome-wide research into clinical practice and interpretation of their results.

Reception time: Wed, Fri 16-19

Head of
"Neurology"

Sharkov
Artem Alekseevich

Sharkov Artyom Alekseevich– neurologist, epileptologist

In 2012, he studied under the international program “Oriental medicine” at Daegu Haanu University in South Korea.

Since 2012 - participation in organizing the database and algorithm for interpreting genetic tests xGenCloud (http://www.xgencloud.com/, Project Manager - Igor Ugarov)

In 2013 he graduated from the Pediatric Faculty of the Russian National Research Medical University named after N.I. Pirogov.

From 2013 to 2015, he studied at a clinical residency in neurology at the Federal State Budgetary Institution "Scientific Center of Neurology".

Since 2015, he has been working as a neurologist and researcher at the Scientific Research Clinical Institute of Pediatrics named after Academician Yu.E. Veltishchev GBOU VPO RNIMU im. N.I. Pirogov. He also works as a neurologist and a doctor in the video-EEG monitoring laboratory at the clinics of the Center for Epileptology and Neurology named after. A.A. Kazaryan" and "Epilepsy Center".

In 2015, he completed training in Italy at the school “2nd International Residential Course on Drug Resistant Epilepsies, ILAE, 2015”.

In 2015, advanced training - “Clinical and molecular genetics for medical practitioners”, RDKB, RUSNANO.

In 2016, advanced training - “Fundamentals of molecular genetics” under the guidance of a bioinformatician, Ph.D. Konovalova F.A.

Since 2016 - head of the neurological direction of the Genomed laboratory.

In 2016, he completed training in Italy at the school “San Servolo international advanced course: Brain Exploration and Epilepsy Surger, ILAE, 2016”.

In 2016, advanced training - “Innovative genetic technologies for doctors”, “Institute of Laboratory Medicine”.

In 2017 – school “NGS in Medical Genetics 2017”, Moscow State Research Center

Currently conducting scientific research in the field of genetics of epilepsy under the guidance of Professor, Doctor of Medical Sciences. Belousova E.D. and professor, doctor of medical sciences. Dadali E.L.

The topic of the dissertation for the degree of Candidate of Medical Sciences “Clinical and genetic characteristics of monogenic variants of early epileptic encephalopathies” has been approved.

The main areas of activity are the diagnosis and treatment of epilepsy in children and adults. Narrow specialization – surgical treatment of epilepsy, genetics of epilepsy. Neurogenetics.

Scientific publications

Sharkov A., Sharkova I., Golovteev A., Ugarov I. “Optimization of differential diagnosis and interpretation of genetic testing results using the XGenCloud expert system for some forms of epilepsy.” Medical Genetics, No. 4, 2015, p. 41.
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Sharkov A.A., Vorobyov A.N., Troitsky A.A., Savkina I.S., Dorofeeva M.Yu., Melikyan A.G., Golovteev A.L. "Epilepsy surgery for multifocal brain lesions in children with tuberous sclerosis." Abstracts of the XIV Russian Congress "INNOVATIVE TECHNOLOGIES IN PEDIATRICS AND CHILDREN'S SURGERY." Russian Bulletin of Perinatology and Pediatrics, 4, 2015. - p.226-227.
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Dadali E.L., Belousova E.D., Sharkov A.A. "Molecular genetic approaches to the diagnosis of monogenic idiopathic and symptomatic epilepsies." Thesis of the XIV Russian Congress "INNOVATIVE TECHNOLOGIES IN PEDIATRICS AND CHILDREN'S SURGERY." Russian Bulletin of Perinatology and Pediatrics, 4, 2015. - p.221.
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Sharkov A.A., Dadali E.L., Sharkova I.V. “A rare variant of early epileptic encephalopathy type 2 caused by mutations in the CDKL5 gene in a male patient.” Conference "Epileptology in the system of neurosciences". Collection of conference materials: / Edited by: prof. Neznanova N.G., prof. Mikhailova V.A. St. Petersburg: 2015. – p. 210-212.
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Dadali E.L., Sharkov A.A., Kanivets I.V., Gundorova P., Fominykh V.V., Sharkova I.V. Troitsky A.A., Golovteev A.L., Polyakov A.V. A new allelic variant of myoclonus epilepsy type 3, caused by mutations in the KCTD7 gene // Medical Genetics. - 2015. - Vol. 14. - No. 9. - p. 44-47
*
Dadali E.L., Sharkova I.V., Sharkov A.A., Akimova I.A. “Clinical and genetic features and modern methods for diagnosing hereditary epilepsies.” Collection of materials “Molecular biological technologies in medical practice” / Ed. Corresponding member RAIN A.B. Maslennikova.- Issue. 24.- Novosibirsk: Akademizdat, 2016.- 262: p. 52-63
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Belousova E.D., Dorofeeva M.Yu., Sharkov A.A. Epilepsy in tuberous sclerosis. In "Brain diseases, medical and social aspects" edited by Gusev E.I., Gekht A.B., Moscow; 2016; pp.391-399
*
Dadali E.L., Sharkov A.A., Sharkova I.V., Kanivets I.V., Konovalov F.A., Akimova I.A. Hereditary diseases and syndromes accompanied by febrile seizures: clinical and genetic characteristics and diagnostic methods. //Russian Journal of Child Neurology.- T. 11.- No. 2, p. 33- 41. doi: 10.17650/ 2073-8803-2016-11-2-33-41
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Sharkov A.A., Konovalov F.A., Sharkova I.V., Belousova E.D., Dadali E.L. Molecular genetic approaches to the diagnosis of epileptic encephalopathies. Collection of abstracts “VI BALTIC CONGRESS ON CHILD NEUROLOGY” / Edited by Professor Guzeva V.I. St. Petersburg, 2016, p. 391
*
Hemispherotomy for drug-resistant epilepsy in children with bilateral brain damage Zubkova N.S., Altunina G.E., Zemlyansky M.Yu., Troitsky A.A., Sharkov A.A., Golovteev A.L. Collection of abstracts “VI BALTIC CONGRESS ON CHILD NEUROLOGY” / Edited by Professor Guzeva V.I. St. Petersburg, 2016, p. 157.
*
*
Article: Genetics and differentiated treatment of early epileptic encephalopathies. A.A. Sharkov*, I.V. Sharkova, E.D. Belousova, E.L. Yes they did. Journal of Neurology and Psychiatry, 9, 2016; Vol. 2doi: 10.17116/jnevro 20161169267-73
*
Golovteev A.L., Sharkov A.A., Troitsky A.A., Altunina G.E., Zemlyansky M.Yu., Kopachev D.N., Dorofeeva M.Yu. "Surgical treatment of epilepsy in tuberous sclerosis" edited by Dorofeeva M.Yu., Moscow; 2017; p.274
*
New international classifications of epilepsies and epileptic seizures of the International League Against Epilepsy. Journal of Neurology and Psychiatry. C.C. Korsakov. 2017. T. 117. No. 7. P. 99-106

Head of
"Prenatal diagnosis"

Kyiv
Yulia Kirillovna

In 2011 she graduated from the Moscow State Medical and Dental University. A.I. Evdokimova with a degree in General Medicine. She studied residency at the Department of Medical Genetics of the same university with a degree in Genetics.

In 2015, she completed an internship in Obstetrics and Gynecology at the Medical Institute for Advanced Training of Physicians of the Federal State Budgetary Educational Institution of Higher Professional Education "MSUPP"

Since 2013, he has been conducting consultations at the State Budgetary Institution "Center for Family Planning and Reproduction" of the Department of Health.

Since 2017, he has been the head of the “Prenatal Diagnostics” direction of the Genomed laboratory

Regularly makes presentations at conferences and seminars. Gives lectures for various specialist doctors in the field of reproduction and prenatal diagnostics

Provides medical and genetic counseling to pregnant women on prenatal diagnostics in order to prevent the birth of children with congenital malformations, as well as families with presumably hereditary or congenital pathologies. Interprets the obtained DNA diagnostic results.

SPECIALISTS

Latypov
Arthur Shamilevich

Latypov Artur Shamilevich is a geneticist doctor of the highest qualification category.

After graduating from the medical faculty of the Kazan State Medical Institute in 1976, he worked for many years, first as a doctor in the office of medical genetics, then as the head of the medical-genetic center of the Republican Hospital of Tatarstan, the chief specialist of the Ministry of Health of the Republic of Tatarstan, and as a teacher in the departments of the Kazan Medical University.

Author of more than 20 scientific papers on problems of reproductive and biochemical genetics, participant in many domestic and international congresses and conferences on problems of medical genetics. He introduced methods of mass screening of pregnant women and newborns for hereditary diseases into the practical work of the center, and performed thousands of invasive procedures for suspected hereditary diseases of the fetus at different stages of pregnancy.

Since 2012, she has been working at the Department of Medical Genetics with a course in prenatal diagnostics at the Russian Academy of Postgraduate Education.

Area of ​​scientific interests: metabolic diseases in children, prenatal diagnostics.

Doctors are seen by appointment.

Geneticist

Gabelko
Denis Igorevich

In 2009 he graduated from the Faculty of Medicine of KSMU named after. S. V. Kurashova (specialty “General Medicine”).

Internship at the St. Petersburg Medical Academy of Postgraduate Education of the Federal Agency for Health and Social Development (specialty “Genetics”).

Internship in Therapy. Primary retraining in the specialty “Ultrasound diagnostics”. Since 2016, he has been an employee of the department of the Department of Fundamental Principles of Clinical Medicine of the Institute of Fundamental Medicine and Biology.

Area of ​​professional interests: prenatal diagnosis, the use of modern screening and diagnostic methods to identify genetic pathology of the fetus. Determining the risk of recurrence of hereditary diseases in the family.

Participant of scientific and practical conferences on genetics and obstetrics and gynecology.

Work experience 5 years.

Doctors are seen by appointment.

Geneticist

Grishina
Kristina Alexandrovna

She graduated from the Moscow State Medical and Dental University in 2015 with a degree in General Medicine. In the same year, she entered residency in the specialty 08/30/30 “Genetics” at the Federal State Budgetary Institution “Medical Genetic Research Center”.
She was hired at the Laboratory of Molecular Genetics of Complexly Inherited Diseases (headed by Dr. A.V. Karpukhin) in March 2015 as a research assistant. Since September 2015, she has been transferred to the position of research assistant. He is the author and co-author of more than 10 articles and abstracts on clinical genetics, oncogenetics and molecular oncology in Russian and foreign journals. Regular participant in conferences on medical genetics.

Area of ​​scientific and practical interests: medical and genetic counseling of patients with hereditary syndromic and multifactorial pathology.

A consultation with a geneticist allows you to answer the following questions:

Are the child’s symptoms signs of a hereditary disease? what research is needed to identify the cause determining an accurate forecast recommendations for conducting and evaluating the results of prenatal diagnostics everything you need to know when planning a family consultation when planning IVF on-site and online consultations

took part in the scientific and practical school "Innovative genetic technologies for doctors: application in clinical practice", the conference of the European Society of Human Genetics (ESHG) and other conferences dedicated to human genetics.

Conducts medical and genetic counseling for families with suspected hereditary or congenital pathologies, including monogenic diseases and chromosomal abnormalities, determines indications for laboratory genetic studies, and interprets the results of DNA diagnostics. Consults pregnant women on prenatal diagnostics to prevent the birth of children with congenital malformations.

Geneticist, obstetrician-gynecologist, candidate of medical sciences

Kudryavtseva
Elena Vladimirovna

Geneticist, obstetrician-gynecologist, candidate of medical sciences.

Specialist in the field of reproductive counseling and hereditary pathology.

Graduated from the Ural State Medical Academy in 2005.

Residency in Obstetrics and Gynecology

Internship in the specialty "Genetics"

Professional retraining in the specialty “Ultrasound diagnostics”

Activities:

• Infertility and miscarriage
Vasilisa Yurievna



She is a graduate of the Nizhny Novgorod State Medical Academy, Faculty of Medicine (specialty “General Medicine”). She graduated from clinical residency at FBGNU "MGNC" with a degree in Genetics. In 2014, she completed an internship at the Maternity and Childhood Clinic (IRCCS materno infantile Burlo Garofolo, Trieste, Italy).

Since 2016, he has been working as a consultant physician at Genomed LLC.

Regularly participates in scientific and practical conferences on genetics.

Main activities: Consulting on clinical and laboratory diagnostics of genetic diseases and interpretation of results. Management of patients and their families with suspected hereditary pathology. Consulting when planning pregnancy, as well as during pregnancy, on prenatal diagnostics in order to prevent the birth of children with congenital pathologies.

Genetic analysis - the path to precise treatment

An integral part of traditional oncology treatment is the effect on the entire body with the help of chemotherapy drugs. However, the clinical effect of this treatment is not always high enough. This happens due to the complex mechanism of cancer and individual differences in patients' bodies, their response to treatment and the number of complications. To improve the effectiveness of treatment in general, the world has begun to pay more and more attention to the individualization of treatment.

Individual selection of treatment in oncology has become of great importance following the development and introduction of targeted drugs into widespread clinical practice, and genetic analysis helps to select them correctly.

Individual treatment– this is, first of all, precise treatment of a specific tumor. There is no need to explain why treatment must be carried out precisely. Therefore, obtaining more useful information about the body gives hope for life: 76% of cancer patients have certain variants of gene mutations. Genetic tests will help find this target, eliminate ineffective treatment, so as not to lose the most productive time for treatment. And also reduce the physical and psychological burden of the patient and his family.

Genetic tests for oncology are tests that determine mutations in genes that establish DNA and RNA sequences. Each tumor has its own individual genetic profile. Genetic analysis helps select targeted therapy drugs that are suitable specifically for your type of tumor. And they will help you make a choice in favor of more effective treatment. For example, in patients with non-small cell lung cancer with an EGFR mutation, the effectiveness of treatment with Gefitinib is 71.2%, and the effectiveness of chemotherapy with Carboplatin + Paclitaxel is 47.3%. If the EGFR value is negative, the effectiveness of Gefitinib is 1.1%, that is, the drug is not effective. Analysis of this mutation directly makes it clear which treatment is best to choose...

Who is suitable for genetic testing?

• Patients in the early stages of cancer.

With the help of genetic tests, you can accurately select the most effective drug, which will avoid wasting time and unnecessary stress on the body.

• Patients in the later stages of cancer.

The selection of effective targeted therapy can significantly prolong the life of patients with advanced stages, whose treatment with traditional methods is no longer possible.

• Patients with rare types of cancer or cancer of unknown origin.

In such cases, the selection of standard treatment is very difficult, and genetic tests make it possible to select an accurate treatment even without determining the specific type of cancer.

• Patients whose situation cannot be treated with traditional methods.

It is a good choice for patients who have exhausted traditional treatment options because genetic testing can identify a range of additional drugs that can be used.

• Patients with relapses. Genetic tests are recommended to be retested in case of relapses because gene mutations may change. And then, based on new genetic analyses, new targeted therapy drugs will be selected.

Genetic tests in Harbin

In China, a country with high rates of cancer incidence, individualization of treatment has become widely accepted, and genetic tests for selecting targeted therapy have become firmly established in clinical practice. In Harbin, genetic tests are carried out at the Oncology Department of Heilongjiang Nongken Central Hospital.

The most informative way to go full range of genetic tests is second-generation sequencing performed using high-density neutron flux. The technology of second-generation genetic analyzes makes it possible to test 468 important tumor genes at a time; it is possible to identify all types of all genetic regions related to the tumor, and detect special types of its gene mutations.

The complex includes:

• Direct genes for targeted drugs – more than 80 genes

FDA-approved drug targets and experimental drug targets are identified.

• Genes that determine drug pathways to targets - more than 200 genes
• Genes that repair DNA - more than 50 genes

Radiation and chemotherapy, PARP inhibitors, immune therapy

• Indicative hereditary genes - about 25 genes

Relevant to certain targets and efficacy of chemotherapy.

• Other high frequency mutating genes

Related to prognosis and diagnosis.

Why do I need to check so many indicators if my cancer type is already known?

Due to the large number of patients, Chinese oncologists have traditionally gone further than their colleagues from other countries in the development and use of targeted therapy.

Studies of targeted therapy in various variations of its application have led to interesting results. Different targeted drugs act on the corresponding gene mutations. But the gene mutations themselves, as it turns out, are not so strictly tied to a particular type of cancer.

For example, in a patient with liver cancer, after a full range of genetic tests, a mutation was identified in which the drug Iressa, intended for lung cancer, shows a high effect. Treatment of this patient with a drug for lung cancer led to regression of the liver tumor! This and other similar cases gave a completely new meaning to the definition of genetic mutations.

Currently, checking a full range of genetic tests makes it possible to expand the list of targeted therapy drugs with those drugs that were not originally intended for use, which significantly increases the clinical effectiveness of treatment.

Genetic tests are determined by tumor tissue (this is preferable! Tumor material after surgery or after a puncture biopsy is suitable) or by blood (blood from a vein).

To more accurately determine gene mutations, especially in case of relapses, it is recommended to perform a repeat biopsy with the collection of new tumor material. If a biopsy is impractical or risky, then the test is performed using venous blood.

The result is ready in 7 days. The conclusion contains not only the result, but also specific recommendations with the names of suitable drugs.

You have probably asked this question more than once if one of your relatives was diagnosed with cancer. Many people are at a loss - what to do if grandmothers and great-grandmothers died at the age of 30-40, and there is no information about their diseases? And if they died at 60 “of old age,” like everyone else at that time, was it cancer? Could it happen to me?

When a relative gets cancer, we are scared. To some extent, I’m also scared about my health - is cancer inherited? Before jumping to conclusions and panicking, let's understand this issue.

Over the past decades, scientists around the world have been closely studying cancer and have even learned to treat some of its types. Important discoveries are also taking place in the field of genetics, for example, at the end of last year, German molecular biologists discovered the cause of about a third of cancer cases. Geneticists have been able to identify the causes of chromothripsis, the so-called “chromosomal chaos”. With it, the chromosomes fall apart, and if they are accidentally reunited, the cell either dies or becomes the beginning of a cancerous tumor.

At the clinic, we try to actively apply the achievements of geneticists in everyday practice: we determine predisposition to various types of cancer and the presence of mutations using genetic studies. If you are part of a risk group - we will talk about it a little later - you should pay attention to these studies. In the meantime, let's return to the question.

At its core, cancer is a genetic disease that occurs as a result of a breakdown in the cell's genome. Over and over again, a consistent accumulation of mutations occurs in the cell, and it gradually acquires malignant properties - it becomes malignant.

There are several genes that are involved in the breakdown, and they do not stop working at the same time.

• Genes that encode growth and division systems are called proto-oncogenes. When they break down, the cell begins to endlessly divide and grow.
• There are tumor suppressor genes that are responsible for the system that senses signals from other cells and inhibits growth and division. They can inhibit cell growth, and when they break down, this mechanism is turned off.
• And finally, there are DNA repair genes, which code for proteins that repair DNA. Their breakdown contributes to the very rapid accumulation of mutations in the cell genome.

Genetic predisposition to cancer

There are two scenarios for the occurrence of mutations that cause cancer: non-hereditary and hereditary. Non-hereditary mutations appear in initially healthy cells. They occur under the influence of external carcinogenic factors, such as smoking or ultraviolet radiation. Cancer mainly develops in people in adulthood: the process of occurrence and accumulation of mutations can take several decades.

However, in 5-10% of cases, heredity plays a predetermining role. This happens when one of the oncogenic mutations appears in a germ cell that is lucky enough to become a human. In this case, each of approximately 40 * 1012 cells of this person’s body will also contain the initial mutation. Therefore, each cell would need to accumulate fewer mutations to become cancerous.

An increased risk of developing cancer is passed on from generation to generation and is called hereditary tumor syndrome. This syndrome occurs quite often - in approximately 2-4% of the population.

Despite the fact that the bulk of cancer is caused by random mutations, the hereditary factor also needs to be given serious attention. Knowing about existing inherited mutations can prevent the development of a specific disease.

Almost every cancer has hereditary forms. Tumor syndromes are known that cause cancer of the stomach, intestines, brain, skin, thyroid gland, uterus and other, less common types of tumors. These same types may not be hereditary, but sporadic (single, occurring from time to time).

Predisposition to cancer is inherited as a Mendelian dominant trait, in other words, as a common gene with varying frequencies of occurrence. Moreover, the likelihood of occurrence at an early age in hereditary forms is higher than in sporadic ones.

Common genetic studies

We will briefly tell you about the main types of genetic studies that are indicated for people at risk. All these studies can be carried out in our clinic.

Determination of mutation in the BRCA gene

In 2013, thanks to Angelina Jolie, the whole world actively discussed hereditary breast and ovarian cancer; even non-specialists now know about mutations in the BRCA1 and BRCA2 genes. Due to mutations, the functions of the proteins encoded by these genes are lost. As a result, the main mechanism of repair (restoration) of double-strand breaks in the DNA molecule is disrupted, and a state of genomic instability arises - a high frequency of mutations in the genome of the cell line. Genomic instability is a central factor in carcinogenesis.

In simple terms, the BRCA1/2 genes are responsible for repairing DNA damage, and mutations in these genes disrupt this very repair, thus the stability of genetic information is lost.

Scientists have described more than a thousand different mutations in these genes, many of which (but not all) are associated with an increased risk of cancer.

Women with BRCA1/2 abnormalities have a 45-87% risk of developing breast cancer, while the average risk is only 5.6%. The likelihood of developing malignant tumors in other organs also increases: the ovaries (from 1 to 35%), the pancreas, and in men, the prostate gland.

Genetic predisposition to hereditary nonpolyposis colorectal cancer (Lynch syndrome)

Colorectal cancer is one of the most common cancers in the world. About 10% of the population has a genetic predisposition to it.

A genetic test for Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer (HNPCC), detects the disease with 97% accuracy. Lynch syndrome is a hereditary disease in which a malignant tumor affects the walls of the large intestine. It is believed that about 5% of all colorectal cancer cases are associated with this syndrome.

Determination of mutation in the BRaf gene

If you have melanoma, thyroid or prostate tumors, ovarian or intestinal tumors, it is recommended (and in some cases mandatory) to test for the BRaf mutation. This study will help choose the necessary tumor treatment strategy.

BRAF is an oncogene that is responsible for encoding a protein located in the Ras-Raf-MEK-MARK signaling pathway. This pathway normally regulates cell division under the control of growth factors and various hormones. A mutation in the BRaf oncogene leads to excessive uncontrolled proliferation and resistance to apoptosis (programmed death). The result is several times accelerated cell reproduction and tumor growth. Based on the evidence from this study, the specialist concludes that it is possible to use BRaf inhibitors, which have demonstrated significant advantages compared to standard chemotherapy.

Analysis methodology

Any genetic analysis is a complex multi-step procedure.
Genetic material for analysis is taken from cells, usually blood cells. But recently, laboratories are moving to non-invasive methods and sometimes extracting DNA from saliva. The isolated material is subjected to sequencing - determination of the sequence of monomers using chemical analyzers and reactions. This sequence is the genetic code. The resulting code is compared with the reference one and it is determined which sections belong to which genes. Based on their presence, absence or mutation, a conclusion is made about the test results.

Today there are many methods of genetic analysis in laboratories, each of them is good in certain situations:

• FISH method (fluorescence in situ hybridization). A special dye is injected into the biomaterial obtained from the patient - a DNA sample with fluorescent labels that can show chromosomal aberrations (deviations) that are significant for determining the presence and prognosis of the development of certain malignant processes. For example, the method is useful in determining copies of the HER-2 gene, an important trait in the treatment of breast cancer.
• Comparative genomic hybridization (CGH) method. The method allows you to compare the DNA of the patient's healthy tissue and tumor tissue. An accurate comparison makes it clear which parts of the DNA are damaged, and this provides tools for choosing targeted treatment.
• Next-generation sequencing (NGS) - unlike earlier sequencing methods, it “can read” several sections of the genome at once, and therefore speeds up the process of “reading” the genome. It is used to determine polymorphisms (replacement of nucleotides in the DNA chain) and mutations associated with the development of malignant tumors in certain parts of the genome.

Due to the large number of chemical reagents, genetic research procedures are quite financially expensive. We try to establish the optimal cost of all procedures, so our price for such research starts from 4,800 rubles.

At-risk groups

People who have at least one of the following factors are at risk for hereditary cancer:

• Multiple cases of the same type of cancer in a family
  (for example, stomach cancer in a grandfather, father and son);
• Diseases at an early age for this indication
  (eg, colorectal cancer in a patient under 50 years of age);
• A single case of a specific type of cancer
  (eg, ovarian cancer, or triple negative breast cancer);
• Cancer in each of the paired organs
  (for example, cancer of the left and right kidney);
• A relative has more than one type of cancer
  (for example, a combination of breast cancer and ovarian cancer);
• Cancer uncharacteristic of the patient's gender
  (for example, breast cancer in a man).

If at least one factor from the list is typical for a person and his family, then you should consult a geneticist. He will determine whether there are medical indications for taking a genetic test.

To detect cancer at an early stage, carriers of hereditary tumor syndrome should undergo thorough cancer screening. In some cases, the risk of developing cancer can be significantly reduced through preventive surgery and drug prophylaxis.

The genetic “look” of a cancer cell changes during development and loses its original appearance. Therefore, to use the molecular features of cancer for treatment, it is not enough to study only inherited mutations. Molecular testing of samples obtained from biopsy or surgery is necessary to identify weak points in the tumor.

During the test, the tumor is analyzed and an individual molecular passport is compiled. In combination with a blood test, depending on the required test, a combination of various genome and protein tests is carried out. As a result of this test, it becomes possible to prescribe targeted therapy that is effective for each type of tumor present.

Prevention

There is an opinion that to determine predisposition to cancer, you can do a simple analysis for the presence of tumor markers - specific substances that can be waste products of the tumor.

However, more than half of oncologists in our country admit that this indicator is not informative for prevention and early detection - it gives too high a percentage of false-positive and false-negative results.

An increase in the rate may depend on a number of reasons completely unrelated to cancer. At the same time, there are examples of people with cancer whose tumor marker values ​​remained within normal limits. Experts use tumor markers as a method to track the progress of an already detected disease, the results of which need to be rechecked.

To identify the likelihood of genetic inheritance, first of all, if you are at risk, you need to consult an oncologist. The specialist, based on your medical history, will draw a conclusion about the need to conduct certain studies.

It is important to understand that the decision to conduct any test must be made by the doctor. Self-medication in oncology is unacceptable. Incorrectly interpreted results can not only cause premature panic, but you may simply miss the presence of developing cancer. Detecting cancer at an early stage with timely and correct treatment gives a chance for recovery.

Should we panic?

Cancer is an inevitable companion of a long-lived organism: the probability of a somatic cell accumulating a critical number of mutations is directly proportional to its lifespan. Just because cancer is a genetic disease does not mean it is hereditary. It is transmitted in 2-4% of cases. If your relative is diagnosed with cancer, do not panic, this will harm both yourself and him. Contact your oncologist. Complete the studies he assigns to you. It is better if it is a specialist who monitors progress in the field of cancer diagnosis and treatment and is aware of everything you have just learned. Follow his recommendations and don’t get sick.

Molecular genetic testing is an integral part of the examination and treatment of cancer patients around the world.

The reason for the appearance of a tumor is mutations, i.e. genetic disorders that occur in one of the billions of cells in the human body. These mutations disrupt the normal functioning of cells, which leads to their uncontrolled and unlimited growth, reproduction and spread throughout the body - metastasis. However, the presence of such mutations makes it possible to distinguish tumor cells from healthy ones and use this knowledge in the treatment of patients.

Analysis of the tumor of each individual patient and the formation of an individual list of potential target molecules became possible thanks to the introduction of molecular genetic analysis techniques into clinical practice. Scientific Laboratory of Molecular Oncology National Medical Research Center of Oncology named after. N.N. Petrova performs a full range of modern molecular genetic studies for cancer patients and their relatives.

Who can benefit from genetic research and how?

• For patients with an established cancer diagnosis, it will help select effective drug therapy.
• For patients under 50 years of age diagnosed with breast cancer, ovarian cancer, stomach cancer or pancreatic cancer, determine the presence of cancer predisposition and adjust treatment.
• Healthy people with an unfavorable family “oncological history” should determine the presence of an oncological predisposition and take preventive measures in advance to detect the tumor early.

National Medical Research Center of Oncology named after. N.N. Petrova carries out a full range of activities related to the diagnosis of hereditary predisposition to breast cancer.

Any person is a carrier of some mutations that are dangerous either for us or for our offspring. The first direction of research by oncogeneticists is the identification of hereditary mutations using genome sequencing. The second direction is the study of the tumor itself, the spectrum of mutations acquired by the cell, in connection with which it arose. This also requires a study of the genome of the entire organism to compare the DNA sequence of the tumor with the DNA sequence in the body. Therefore, in the future it will be needed to treat any tumor.

Molecular genetic studies can be done remotely

In order to undergo a genetic examination at the National Medical Research Center of Oncology. N.N. Petrova does not have to come to St. Petersburg. The Scientific Laboratory of Molecular Oncology accepts research materials by mail. You can send the item by letter or parcel post either by Russian Post (average delivery time is 2 weeks) or by express mail (delivery time 2-3 days).

Please carefully read the information about where and how to send biological materials so that they reach the National Medical Research Center of Oncology named after. N.N. Petrov, as well as how to pay for research and get results:

• all pathomorphological materials: paraffin blocks and glasses. If the quality of the sections is poor or to identify important details, additional sections may be needed;
• deoxygenated blood.

• a referral letter for molecular genetic testing completed by a doctor
• copies of the patient's and payer's passports - a spread with basic information + registration (required to provide a payment receipt)
• Contact Information:
  - mobile phone number (for SMS notification about the readiness of the analysis)
  - email address (to send the result by email)
• a copy of the discharge summary or consultation report (if available)
• copy of the histological report of the provided material (if available)

Price:

Prices for molecular genetic studies are indicated in the price list, section 11.9

What molecular genetic studies require the patient’s blood:

• hereditary mutations (BRCA1,2, etc.)
• polymorphism UGT1A1*28
• detection of codeletion 1p/19q + blocks and glasses
• confirmation that the pathological material belongs to the patient

Features of sending blood tubes

• The required volume of venous blood is 3-5 ml.
• Blood sampling can be done at any time of the day, regardless of food intake.
• Blood is collected into EDTA tubes (purple cap).
• To mix blood with the anticoagulant with which the tube is coated from the inside, the closed tube must be smoothly turned upside down several times.
• At room temperature, a tube of blood can be transported for two weeks.

Important! Returns of blocks and glass by mail are temporarily not accepted. You must pick up your materials at the National Medical Research Center of Oncology yourself, or the patient’s representative by proxy.

Don't forget to include documents in the parcel. Be sure to leave your phone number and email address.