home Audience 6 Scientific electronic library. Tumors. General characteristics. Cancer risk factors Cancer risk factors

Scientific electronic library. Tumors. General characteristics. Cancer risk factors Cancer risk factors

According to the forecasts of the World Health Organization (WHO), during the period from 1999 to 2020, the incidence of malignant neoplasms and mortality from them worldwide will increase by 2 times: from 10 to 20 million new cases per year and from 6 to 12 million recorded deaths, respectively. Considering that in developed countries there is a downward trend in these indicators (both through prevention, primarily the fight against smoking, and through improving the methods of early diagnosis and treatment), it becomes clear that the main increase will come from developing countries, which today Russia should also be included. Unfortunately, in Russia we should expect a serious increase in both the incidence of cancer and mortality from malignant tumors. This prediction is confirmed by data on the main causes of oncological diseases.

The first places in the structure of the incidence of malignant neoplasms of the male population of Russia are distributed as follows: tumors of the trachea, bronchi, lung (18.4%), prostate (12.9%), skin (10.0%, with melanoma - 11.4% ), stomach (8.6%), colon (5.9%). A significant proportion of malignant neoplasms of the rectum, rectosigmoid junction, anus (5.2%), lymphatic and hematopoietic tissue (4.8%), kidney (4.7%), bladder (4.5%), pancreas ( 3.2%), larynx (2.5%). A significant group in terms of specific weight in men is formed by malignant tumors of the genitourinary system, accounting for 22.9% of all malignant neoplasms.

Breast cancer (20.9%) is the leading oncological pathology in the female population, followed by neoplasms of the skin (14.3%, with melanoma - 16.2%), uterine body (7.7%), colon (7, 0%), stomach (5.5%), cervix (5.3%), rectum, rectosigmoid junction, anus (4.7%), ovary (4.6%).

Early diagnosis of malignant neoplasms depends mainly on the oncological vigilance of general practitioners and their knowledge, further tactics in relation to the patient. In 1994 The European Commission for Cancer Research (EUROPEAN GUIDELINES FOR QUALITY ASSURANCE IN MAMMOGRAPHY SCREENING), at a special conference on the role of the therapist and surgeon in cancer screening, highly appreciated the role of the practitioner, in our country - the general practitioner. It is difficult to overestimate the value of a general practitioner. The constant work of oncological dispensaries with general practitioners and the public, aimed at early detection of malignant neoplasms, is an important component that can increase the level of early diagnosis of cancer of various localizations.

Improving sanitary and educational work, dispensary examination of the population, timely treatment of patients with suspicion of various pathologies, the use of a comprehensive examination of the population, will improve the timely diagnosis of malignant neoplasms and treatment results.

Thus, the main task of the doctor in his work on the prevention of oncological pathology is the timely recognition and treatment of precancerous conditions against which cancer develops, as well as the early diagnosis of malignant neoplasms.

Primary prevention

Primary cancer prevention (PPR) should play a leading role in reducing cancer incidence.

Primary cancer prevention (PPR) “is understood as a system of social and hygienic measures regulated by the state and the efforts of the population itself, aimed at preventing the occurrence of malignant tumors and their preceding precancerous conditions by eliminating, weakening or neutralizing the impact of adverse factors of the human environment and lifestyle, as well as by increasing the nonspecific resistance of the organism. The system of measures should cover the entire life of a person, starting from the antenatal period. First of all, it is the complete elimination or minimization of contact with carcinogens.”

It is necessary to distinguish between individual and state measures for the prevention of malignant tumors.

Individual prevention

Individual prevention involves awareness of the population about cancer and compliance with a number of rules.

Based on the risk factors for the occurrence of malignant tumors, each person should remember:

●Rational nutrition. Pickles and pickled foods should be excluded from the daily diet, as they contain nitrites and nitrates. To prepare food for the future, instead of canning, it is recommended to use quick freezing. This is what has played a role in reducing the incidence of stomach cancer in the United States. It is necessary to limit the intake of animal fats, smoked and fried foods, increase and diversify the consumption of fresh vegetables and fruits. During periods of shortage of fresh vegetables and fruits, it is advisable to regularly take synthetic vitamins. Clinical observations have shown that taking vitamins A and E reduces the frequency of metaplasia of the stomach epithelium in the intestinal type, has a therapeutic effect in pre-tumor changes in the mucous membranes, in particular, the oral cavity;

● Harm of active and passive smoking. Quitting smoking reduces the risk of cancer by 30%;

●endocrine-metabolic disorders. With obesity and multiple abortions, the risk of developing cancer of the reproductive system organs increases;

●existence of hereditary forms of cancer. With "familial forms" of cancer, timely consultation of the proband's relatives with a specialist doctor is necessary;

● the danger of excessive solar radiation;

● the need to maintain hygiene of the oral cavity and genitals;

●Hazards of excessive consumption of hard liquor. Low-alcohol and medium-strength drinks, such as table grape wines, do not have such a detrimental effect.

Mass prevention

State measures for the primary prevention of cancer consist in controlling the content of carcinogenic and radioactive substances in drinking water, food products, air and soil. The state should solve environmental problems by developing and using filters at enterprises that pollute the atmosphere, increasing the efficiency of internal combustion engines in road transport, using environmentally friendly fuel, eliminating occupational hazards in industries, etc.

Diagnosed in the early stages, malignant tumors of most organs can now be cured in 70-100% of patients.

The basis of early diagnosis of malignant tumors is screening. The goal of screening is to reduce mortality from this pathology through the active early detection and treatment of preclinical forms of cancer.

Any screening program must meet several mandatory requirements:

●The pathology under investigation must be socially significant, i.e. with high morbidity and mortality.

●The screening method must be highly sensitive. Specificity matters less.

●The methodology should be accessible to the general public.

●Desirable minimum price and invasiveness of the procedure.

●The result of screening should be a reduction in mortality from this pathology.

Taking into account these requirements, several oncological diseases have been selected, for the diagnosis of which it is advisable to create screening programs. These include cancer of the breast, cervix, stomach, colon and rectum, prostate, and lung.

Priority areas of real primary cancer prevention in modern Russia

●Anti-cancer education among the population. Creation of a legal and methodological basis for primary cancer prevention.

●Prevention of cancer in high-risk groups.

●Prevention of occupational cancer.

●Regional preventive programs.

●Training of specialists in the field of PPR and improving their skills.

Directions for primary cancer prevention

Direction of PPR	primary goal
Onco-hygienic prevention	Identification and elimination of the possibility of human exposure to carcinogenic environmental factors, correction of lifestyle features
Biochemical prophylaxis (chemoprophylaxis)	Prevention of the blastomogenic effect from exposure to carcinogenic factors by the use of certain chemicals, products and compounds, as well as biochemical monitoring of the action of carcinogens on the human body
Medical genetic prophylaxis	Identification of families with hereditary tumor and precancerous diseases, as well as individuals with chromosomal instability and organization of measures to reduce the risk of tumors, incl. possible exposure to carcinogenic factors
Immunobiological prophylaxis	Identification of individuals with impaired immune status that contribute to the emergence of tumors, taking measures to correct them, protect them from possible carcinogenic effects. Vaccination
Endocrine-age prevention	Identification of dyshormonal conditions, as well as age-related homeostasis disorders that contribute to the emergence and development of tumors, and their correction

When ranking the main causes that form the incidence of cancer, the leading position is occupied by malnutrition (up to 35%), the second place belongs to smoking (up to 32%).

Thus, 2/3 of cancer cases are due to these factors. Further, in descending order of importance, are viral infections (up to 10%), sexual factors (up to 7%), a sedentary lifestyle (up to 5%), occupational carcinogens (up to 4%), alcoholism (up to 3%), and direct environmental pollution. (up to 2%); oncologically burdened heredity (up to 2%); food additives, solar ultraviolet and ionizing radiation (up to 1%). About 5% of cancer cases are due to unknown causes.

Nutrition. There are 6 basic principles of the anti-cancer diet, the observance of which can significantly reduce the risk of developing cancer:

1.Prevention of obesity (overweight is a risk factor for the development of many malignant tumors, including breast cancer and cancer of the uterine body).

2. Decrease in fat intake (with normal physical activity no more than 50-70g of fat per day with all products). Epidemiological studies have established a direct relationship between fat intake and the incidence of breast cancer, colon cancer, and prostate cancer.

3. Mandatory presence in the diet of vegetables and fruits, providing the body with plant fiber, vitamins and substances that have anticarcinogenic effects.

These include:

Yellow and red vegetables containing carotene (carrots, tomatoes, radishes, etc.);

cabbage (especially broccoli, cauliflower and Brussels sprouts); garlic and onion.

4.Regular and sufficient intake of vegetable fiber (up to 35g daily),

which is found in whole grains of cereals, vegetables, fruits. Vegetable fiber binds a number of carcinogens, reduces the time of their contact with the colon by improving motility.

5. Limitation of alcohol consumption. It is known that alcohol is one of the risk factors for the development of cancer of the oral cavity, esophagus, liver and breast.

6. Limiting the consumption of smoked and nitrite-containing foods. Smoked food contains a significant amount of carcinogens. Nitrites are found in sausages and are still often used by manufacturers for tinting in order to give products a marketable appearance.

The impact of dietary factors on cancer development is not well researched and definitive. Assessing the potential role of diet entails measuring the contribution of a diet containing various components that may both protect against cancer and increase the risk of cancer. A systematic review-based assessment of the overall impact of dietary recommendations on cancer prevention has been published by the World Foundation for Cancer Research/American Institute for Cancer Research (WCRF/AICR). Consumption of fruits and non-starchy vegetables has the greatest preventive effect on reducing the risk of developing cancer. In particular, it has been proven that their sufficient consumption reduces the likelihood of developing cancer of the oral cavity, esophagus and stomach. Fruit consumption, but not non-starchy vegetables, is also significantly associated with a reduced risk of lung cancer.

The complexity of establishing links between food intake and cancer risk is illustrated by examples where observational epidemiological studies (case-control and cohort studies) reveal an association between diet and cancer risk, while such an association is not found in randomized controlled trials. For example, based on population epidemiological data, a high-fiber diet has been recommended for the prevention of colon cancer, and a randomized controlled trial with dietary fiber supplementation (wheat bran) did not reduce the risk of subsequent development of adenomatous polyps in individuals with previous polyp resection. Second, epidemiological cohort and case-control studies have found an association between fat and red meat intake and risk of colon cancer, but a randomized controlled trial found no such association in postmenopausal women. These examples do not negate the results of all cohort studies and case-control studies, especially those conducted over many years, but only show the complexity of the problem of studying the effect of diet on the risk of developing tumors. Relatively short controlled randomized clinical trials are unable to identify the effects of long-term dietary habits on the risk of developing malignant neoplasms.

Smoking. Numerous scientific studies have established a strong link between tobacco use and malignant neoplasms. In particular, epidemiological studies have shown that cigarette smoking is a causal factor in the development of lung cancer, oral cavity, esophagus, bladder, kidney, pancreas, stomach, cervix and acute myeloid leukemia. At the same time, convincing evidence was obtained that an increase in the prevalence of smoking among the population entails an increase in cancer mortality and, conversely, a decrease in the prevalence of smoking reduces the mortality rate from lung cancer in men.

1. Nitrites, nitrates, salts of heavy metals (arsenic, beryllium, cadmium, lead, nickel, etc.) of drinking water and food products: enhance the effect of carcinogens and are material for the endogenous synthesis of carcinogens (kytroso compounds)

a) overweight - the cause of an increased level of estrogens, synthesized mainly by adipose tissue (peripheral aromatization);

b) stimulation of bile production (changes in the intestinal flora, the formation of carcinogens from cholesterol and fatty acids)

3. Canned foods, dried fish (contain neither grains, nitrites), smoked foods (contain polycyclic hydrocarbons)

4. Cooked carbohydrates, combining with amines of gastric juice, lead to the formation of nitroso compounds

5). Dflotoxins (peanuts, cereals)

According to the Ministry of Health of Russia in the Russian Federation annually about 300 thousand. able-bodied people do not survive about five years of their lives due to tobacco consumption, while economic losses amount to almost 1.5 trillion rubles. Smoking cessation leads to a gradual decrease in the risk of developing cancer, to an increase in life expectancy, and a decrease in overall morbidity and mortality.

Infections. In developing countries, infectious agents are responsible for 26%, and in developed countries, 8% of all cancer cases. Infection with a strain of human papillomavirus (HPV) of high oncogenic risk (types 16, 18, 31, 33) is considered as a necessary event for the subsequent development of cervical cancer, and vaccination against HPV leads to a marked reduction in precancerous conditions. Oncogenic strains of HPV are also associated with cancers of the penis, vagina, anus, and oropharynx. Other infectious agents that cause cancer include hepatitis B and hepatitis C virus (liver cancer), Epstein-Barr virus (Burkitt's lymphoma), and Helicobacter pylori (stomach cancer).

Ionizing and ultraviolet radiation. Exposure to radiation, primarily ultraviolet radiation and ionizing radiation, is a well-established cause of cancer. Exposure to solar ultraviolet radiation is the leading cause of skin cancer (not melanoma), which is by far the most common and most preventable malignancy. The most dangerous time is exposure to the sun between 10 am and 4 pm. It is no less harmful to stay in solariums for artificial tanning. Keeping exposed areas of the body out of direct sunlight, wearing appropriate summer clothing, wide-brimmed hats, umbrellas, staying in the shade, and using sunscreen are effective measures to prevent skin cancer.

At present, based on numerous epidemiological and biological studies, it has been convincingly proven that there is no dose of ionizing radiation that should be considered completely safe, for this reason, all measures must be taken to reduce the dose of any ionizing radiation to humans, including those associated with medical research. (fluorography, radiography, fluoroscopy, computed tomography, radioisotope diagnostics and treatment methods) both in relation to patients and medical personnel. Limiting unnecessary therapeutic and diagnostic studies associated with the use of ionizing radiation is an important prevention strategy.

Alcohol. The most significant impact is exerted by excessive consumption of alcohol, especially drinking alcohol, on the development of cancer of the oral cavity, esophagus, breast and colorectal cancer in men. To a lesser extent, such an association exists between alcohol intake and the risk of liver and colorectal cancer in women.

Physical activity. A growing body of evidence suggests that people who are physically active have a lower risk of developing some malignant neoplasms (MNs) compared to people who are physically inactive and lead a sedentary lifestyle. The greatest and most significant protective effect of physical activity was found in relation to the risk of developing colorectal cancer. The “probably” category refers to the impact of physical activity on the risk of developing breast cancer after menopause and endometrial cancer. As for dietary factors, the problem of the influence of physical activity on the development of various malignancies is far from being resolved, but it is quite clear that it plays a significant role in the process of oncogenesis. There is evidence to suggest that physical activity is inversely associated with at least a few of the cancers that obesity promotes.

Obesity. Obesity is increasingly recognized as an important risk factor for cancer.

Its association with the development of postmenopausal breast cancer, cancer of the esophagus, pancreas, colorectal cancer, endometrial and kidney cancer has been convincingly proven. There is evidence that obesity is a risk factor for the development of gallbladder cancer. But at the same time, it should be noted that there are no studies on the effect of reducing excess body weight on mortality from malignant neoplasms.

Vitamins and biologically active food supplements. Vitamins and dietary supplements are preventive interventions with no proven efficacy.

Environmental factors and harmful substances. Some associations between environmental pollutants and the development of lung cancer have been well established, including through secondhand tobacco smoking, outdoor air pollution, especially asbestos dust. Another environmental pollutant that has been causally linked to skin, bladder, and lung cancers is inorganic arsenic in high concentrations in drinking water. Many other environmental contaminants, such as pesticides, have been evaluated for their risk of developing cancer in humans, with indeterminate results.

Occupational hazards Some cancers induced by chemicals are classified as occupational: cancer of workers in hot shops, winemakers (cancer of the hands and feet), cancer in workers with paraffin (cancer of the hands and scrotum), sailors, peasants, many people who are in the air (cancer of the face, hands), cancer when working with aniline substances (cancer of the urinary tract), X-rays (for doctors, personnel of X-ray laboratories), with resins, pitch (for shoemakers - cancer of the finger of the brush), rubber (for workers with rubber cables - cancer of the skin and bladder), in contact with asbestos, chromium, generator gases (lung cancer - contact with asbestos, beryllium, uranium or radon). It is also important that in many cases it is enough to carry out local measures aimed at a specific workshop, technological process, etc. to eliminate occupational carcinogenic exposure. Therefore, the greatest success in the world has been achieved precisely in the field of prevention of malignant tumors associated with the profession.

The main tasks of sanitary and hygienic certification of carcinogenic enterprises

●Creation of territorial regional and federal databases on carcinogen hazardous enterprises.

●Creation of territorial regional and federal register of persons in contact with occupational carcinogenic factors.

●Carrying out preventive measures at enterprises.

genetic factors. A small number of tumors can occur as genetically determined diseases. Dependence on "tumor" genes is associated with the appearance of congenital or hereditary neoplasms. They have been proven for about 50 types of tumors. Dominantly inherited tumors include basaliomas, acoustic neuromas, osteochondromas, multiple lipomas, cervical polyposis, and neurofibromatosis. Plasmacytomas and embryonic nephromas are considered as recessively inherited.

The association between "tumor" and other genes is interesting, for example, an increase in the frequency of stomach cancers in people with blood type A (II). Hereditary neoplasms may occur as congenital or developing immediately after birth, but may develop in older children or even adults.

Relationship between carcinogens

Another aspect to consider is the relationship between carcinogens. For example, it has been shown that an increase in alcohol intake greatly increases the risk of esophageal cancer caused by a risk factor such as smoking. Alcohol, by itself, may facilitate the transport of tobacco or other carcinogens into cells or susceptible tissues. Multiple links can be traced between some carcinogens, such as between exposure to radon decay products and smoking in uranium mine workers. Some exogenous agents may contribute to the development of cancer caused by other agents. This, in particular, refers to the role of dietary fat in the development of breast cancer (obviously due to the increase in the production of hormones, breast stimulants). The opposite effect may also occur. For example, vitamin A delays the development of lung cancer and, possibly, other cancers initiated by tobacco smoking. Similar interrelations can take place between exogenous factors and the constitutional features of the organism. In particular, the genetic polymorphism of enzymes involved in the metabolism of carcinogens or DNA repair is an important point that determines individual susceptibility to the action of exogenous carcinogens.

From a cancer prevention standpoint, the significance of the relationship between carcinogens is that the elimination of exposure to one of two (or more) interrelated factors can provide a greater reduction in cancer incidence than would be expected by taking into account the degree of exposure to this agent in isolation. So, for example, smoking cessation can almost completely eliminate the high incidence of lung cancer in asbestos workers (although the incidence of mesothelioma will not change much).

Secondary prevention

It is aimed at identifying and eliminating precancerous diseases and identifying malignant tumors in the early stages of the process. Studies that allow you to effectively detect precancerous diseases and tumors include: mammography, fluorography, cytological examination of smears from the cervix and cervical canal, endoscopic examinations, preventive examinations, determination of the level of tumor markers in biological fluids, etc.

The development of programs for early diagnosis and screening is one of the priority areas for the development of oncology and can significantly improve treatment outcomes. Regular preventive examinations and examinations in accordance with age (or risk group) can prevent the occurrence of a malignant tumor or detect a disease at an early stage, which allows for effective organ-preserving specialized treatment.

Disease	Research method, frequency	Description	Age of onset
Cervical cancer	Papanicolaou test, once a year	During the examination by a gynecologist, a smear of the mucous membrane of the vagina and cervix is taken. This method also allows diagnosing benign and inflammatory diseases, as well as endometrial cancer.	3 years after the onset of sexual activity
Mammary cancer	Mammography, once a year	X-ray examination of the breast
	Clinical examination, 1 time in 3 years	Palpation examination by a mammologist
	Self-examination, once a year	Palpation examination by a mammologist
Cancer of the colon and rectum (colorectal cancer)	Fecal occult blood test, once a year	Laboratory examination of feces for the presence of blood. If positive, a colonoscopy is performed.
	Sigmoidoscopy and / or sigmoidoscopy 1 time in 3 years	Endoscopic examination of the intestine with a short tube with an integrated camera
	Colonoscopy, 1 time in 10 years	Endoscopic examination of the intestine with a flexible tube with a built-in camera
	Finger examination, 1 time per year	Examination of the rectum with a finger
Prostate cancer	Blood test for PSA (prostate-specific antigen), 1 time per year Digital examination of the rectum, 1 time per year	Finger examination, also effective in the diagnosis of cancer of the rectum and anal canal

The screening methods listed above are effective for early cancer detection and improved outcomes for the entire population, regardless of the presence of risk factors.

However, there are other common cancers for which there is not yet enough evidence for the effectiveness of preventive examinations in the entire population, but screening is certainly indicated for people with certain risk factors. Screening methods were listed that are effective for early detection of cancer and improved outcomes for its treatment for the entire population, regardless of the presence of risk factors.

Tertiary prevention

It consists in the prevention of relapses and metastases in cancer patients, as well as new cases of malignant tumors in cured patients. For the treatment of a malignant tumor and tertiary cancer prevention, only specialized oncological institutions should be contacted. An oncological patient is registered in an oncological institution for life, regularly undergoes the necessary examinations prescribed by specialists.

Currently, one of the youngest and most promising sections of preventive oncology is the chemoprevention of malignant tumors - the reduction of cancer incidence and mortality due to long-term use by healthy people or people from high oncological risk groups of special oncoprophylactic drugs or natural remedies. Chemoprophylaxis must necessarily be used in combination with other preventive measures.

A separate area of prevention in patients with malignant neoplasms is the prevention of complications of chemotherapy arising from the low selectivity of most of the drugs used for these purposes. One of the most common complications of chemotherapy is liver toxicity. Unfortunately, in oncological practice, a drug that adversely affects the liver is not always possible to cancel or replace with another, safer one without creating an immediate or delayed threat to the patient's life. One way out of this difficult situation is the prophylactic use of drugs with hepatoprotective properties, among which S-adenosyl-L-methionine has a good evidence base for its high clinical efficacy.

Currently, cancer risk groups are usually divided into 5 categories according to the degree of risk increase.

1. Practically healthy persons of any age with burdened oncological heredity and people over 45 years old.

2.Practically healthy individuals exposed or exposed to carcinogenic factors. These include smokers, persons in contact with professional and household carcinogenic factors, who have undergone radiation ionizing exposure, and carriers of oncogenic viruses.

3. Persons suffering from chronic diseases and disorders that increase cancer risk: obesity, immune suppression, atherosclerosis, hypertension, type 2 diabetes mellitus, COPD, etc.

4. Patients with obligate and facultative precancerous diseases. The latter are more common and only increase the likelihood of cancer.

5. Oncological patients who have undergone radical treatment for cancer. (This category of patients in accordance with the order of the Ministry of Health of Russia dated November 15, 2012 No. 915n

“The procedure for providing medical care to the population in the field of oncology” - are subject to dispensary observation in an oncological dispensary for life. If the course of the disease does not require a change in the tactics of managing the patient, dispensary examinations after the treatment are carried out: during the first year once every three months, during the second year - once every six months, then - once a year).

EXAMPLE TESTS

Choose one correct answer

1. Rational nutrition for the prevention of oncopathology, all except:

a) for harvesting for the future use freezing products

b) limit the intake of pickles and marinades

c) limit the intake of animal fats

d) limit fruit intake

2. Modifying factors of carcinogenesis do not include:

a) profession

b) lifestyle

c) age

d) bad habits

f) the nature of nutrition

3. Risk factors for oncopathology:

a) obesity

b) multiple abortions

c) alcoholism

d) smoking

d) that's right

SITUATIONAL PROBLEM

Man, 34 years old, worked for 14 years as a molder in a foundry. Occupational hazards: quartz-containing dust (the concentration was 4 times higher than the maximum permissible concentration), elevated air temperature in the room. Smoked up to a pack of cigarettes a day for 13 years. Vanamnesis in a patient with pulmonary tuberculosis (cured).

Objectively: auscultatory examination revealed single dry rales in the lungs. Heart sounds are clear, rhythmic. Heart rate 75bpm. The abdomen is soft and painless on palpation. Stool and diuresis are normal.

Survey results

Plain radiograph of the organs of the chest cavity: a deformation of the pulmonary pattern due to small-spotted shadows of the nodular type was revealed.

EXERCISE

1. Highlight the risk factors for the development of oncopathology in a patient.

2. Calculate the smoker's index?

3. Patient management tactics.

Allocate 4 groups of the most important risk factors contributing to the development of both benign and malignant neoplasms.

1. Aging. An increase in the number of tumors with age is associated with the accumulation of mutations in cells, age-related depression of DNA repair, and physiological age-related immunodeficiency syndrome.

2. Influence of geographical zones and environmental factors (environmental). Morbidity and mortality in different countries from malignant tumors is not the same: for example, from stomach cancer in Japan before the introduction of special prevention measures and early diagnosis, 7-8 times more patients died than in the United States. Of the environmental factors, solar radiation, environmental features, a certain lifestyle of people (smoking, alcoholism, dietary habits and obesity, a large number of sexual partners, especially with an early onset of sexual activity) should be mentioned.

3. Heredity. From 5 to 10% of human malignant tumors are associated with a hereditary predisposition. Hereditary forms of malignant neoplasms are divided into 3 groups: 1) hereditary tumor syndromes; 2) family forms of tumors; 3) autosomal recessive syndromes of impaired DNA repair.

hereditary tumor syndromes. This group includes neoplasms in which the inheritance of a single mutant gene significantly increases the risk of their development. This predisposition refers to an autosomal dominant type of inheritance. The most common example from this group is retinoblastoma (malignant neuroepithelioma of the retina), which is combined in children with colon polyposis.

Familial forms of tumors. Many common types of malignant tumors that occur sporadically are also observed in family forms: colon cancer, breast cancer, ovarian cancer, brain tumors. Common features of the familial form of tumors are the onset at an early age, the appearance of at least two next of kin, the frequent formation of bilateral or multiple lesions.

Autosomal recessive syndromes of impaired DNA repair. We are talking about the instability of the structure of DNA or chromosomes. The group of these syndromes includes xeroderma pigmentosum (pigmentation, hyperkeratosis, edema and other skin changes during sun exposure), Fanconi anemia, characterized by bone marrow hypoplasia, low blood cell count, and many developmental anomalies.

4. Chronic proliferative changes. The background for malignancy (malignancy) can be chronic inflammation, which is often accompanied by focal hyperplasia, metaplasia and dysplasia of the epithelium (these concepts were partially discussed in the chapter on adaptation processes, compensatory-adaptive processes and will also be discussed below when studying tumor morphogenesis).

The pathogenesis of tumors (carcinogenesis)

Currently carcinogenesis is considered as a staged multi-stage process,occurring at the genetic and phenotypic levels, and is accompanied by activation of cellular oncogenes and/or inactivation of anti-oncogenes as a result of damage to the cell genome by carcinogenic agents.

Oncogenes - genes (activated or often defective due to mutations) of inducers of cell division, proliferation and inhibitors of apoptosis. Oncogenes are formed as a result of activation of proto-oncogenes . Proto-oncogenes- normal cell genes; in mature tissues they are usually inactive. The transformation of proto-oncogenes into oncogenes occurs during tumor growth, during embryogenesis, some of them are activated during cell proliferation and differentiation in the foci of reparative regeneration.

Activation of proto-oncogenes occurs by 4 main mechanisms: 1) activation during translocation of a chromosome region with a proto-oncogene embedded in it; 2) insertional activation - activation under the action of special genes built into the genome (for example, viral); 3) activation by amplification (multiplication of copies) of the proto-oncogene; 4) activation in case of point mutations of the proto-oncogene.

Cellular oncogenes code for the synthesis of proteins called oncoproteins, or oncoproteins, which are involved in the transmission of mitogenetic signals from the cell membrane to the nucleus to certain cell genes. This means that most growth factors can interact with oncoproteins to some extent.

Thus, a chain of mechanisms for the activation of proto-oncogenes and the pathogenesis of tumors is built: protooncogene - oncogene - enhanced unbalanced synthesis of oncoproteins - hyperplasia and dysplasia with impaired differentiation and subsequent immortalization of cells - malignant transformation of cells - invasive tumor growth - metastasis.

Antioncogenes or tumor suppressor genes- genes of inhibitors of cell division, proliferation and inducers of apoptosis. Inactivation of tumor growth suppressor genes leads to the loss of their antitumor function, which is expressed in the loss of the ability to inhibit cell proliferation, respectively, the G1 period of the cell cycle is shortened, in which damaged DNA is restored, and apoptosis is not induced. As a result of these processes, the uncontrolled division of tumor cells begins, additional mutations appear in them, which ultimately leads to the development of a malignant tumor. Although dozens of tumor growth suppressor genes are known, mutations of the p53 protein gene, an inhibitor of cell division and a key factor in inducing apoptosis, have the greatest diagnostic value. Mutations in the p53 gene occur in more than half of cancer cases. Defects in another tumor suppressor gene, the p16 protein gene, are almost equally common in tumors.

Pathological anatomy studies the expression of oncogenes, antioncogenes, oncoproteins, etc. using the immunohistochemical method and molecular biology methods. The detection of the expression of many of them in pathoanatomical practice (for example, on biopsy material) makes it possible to clarify the diagnosis of a tumor, predict its biological behavior, and the effectiveness of antitumor treatment. For example, in the pathoanatomical diagnosis of breast cancer, in order to determine the tactics of treatment, it is important to immunohistochemically diagnose the level (severity) of expression of estrogen, progesterone, growth factor receptors and their proliferative activity by tumor cells.

There are three main stages of carcinogenesis - initiation, promotion and progression.

Initiation- initial phase; is that under the action of carcinogens, a mutation of one of the genes that regulates cell reproduction occurs, as a result of which the cell becomes capable of unlimited division, but additional conditions are required for the manifestation of this ability.

Promotion - stimulation by promoters of cell division, which creates a critical mass of initiated cells and promotes their release from tissue control. Promoters can be chemicals that are not carcinogens, but with prolonged exposure to initiated cells, leading to the development of a tumor.

Progression. Tumor growth is not only an increase in the number of homogeneous cells. The tumor is constantly undergoing qualitative changes and acquiring new properties - increasing autonomy from the regulatory influences of the body, destructive growth, invasiveness, the ability to form metastases, and adaptability to changing conditions.

HUMAN AGING. Every person, either from birth or from childhood or adolescence, is a carrier of a tumor. We are talking about: benign nevi, birthmarks, and other nodules in the skin. With aging, the number of nevi may increase, sometimes there are basal cell papillomas, senile warts of the skin. After 55 years, a person enters a period when the likelihood of a malignant neoplasm progressively increases every year. Most cases of death from malignant tumors are noted in the age range from 55 to 74 years.

INFLUENCE OF GEOGRAPHICAL ZONES AND ENVIRONMENTAL FACTORS. There are significant geographic differences in rates of morbidity and mortality from malignant tumors. For example, mortality from stomach cancer in Japan is 7-8 times higher than in the US, and from lung cancer, on the contrary, is 2 times higher in the US than in Japan. Compared to Iceland, skin melanomas are 6 times more common and cause death in New Zealand.

The role of ultraviolet rays (solar radiation), the influence of professional factors, is very important and often manifested in carcinogenesis. When studying risk factors for the development of oncological diseases, much attention is paid to the lifestyle of people: the presence of bad habits, a tendency to various excesses, traditions, eating habits and behavior.

A stronger tumorigenic effect of the combined effect of smoking and alcoholism is known. An important risk factor for developing cervical cancer is considered to be a large number of sexual partners, especially with early onset of sexual activity. It is possible that numerous and poorly studied viral infections of the genital organs play a significant role in this case.

HEREDITY. All inherited forms of malignant neoplasms can be divided into 3 groups: hereditary syndromes of a malignant tumor; familial forms of neoplasia; autosomal recessive syndromes of DNA repair disorders.

Hereditary tumor syndromes are a group of diseases, the manifestation of which is associated with the transmission from generation to generation of an almost fatal predisposition to one or another type of cancer. The most common example is retinoblastoma in children. It has been noted that such carriers have a tendency to form a second tumor, in particular osteosarcoma. Another example is hereditary adenomatous polyposis of the colon, which develops shortly after birth. If children with this disease survive, grow up and live up to 50 years, then in 100% of cases they develop colon cancer.

FAMILY FORMS OF NEOPLASIA. In fact, all common types of malignant tumors that occur sporadically are also observed as familial forms: carcinomas of the intestine, breast, ovarian tumors of the brain. Common signs of familial neoplasm are: onset at an early age, the appearance of at least two or even more immediate relatives, the frequent formation of bilateral or multiple lesions.

AUTOSOMAL RECESSIVE SYNDROME IMPAIRED DNA REPAIR This is an instability of the structure of DNA or chromosomes. The group of these syndromes includes: xeroderma pigmentosa (pigmentation, hyperkeratosis, edema and other skin changes during solar exposure), Fanconi anemia, characterized by bone marrow hypoplasia, low blood cell count, and many anomalies.

TUMOR ANGIOGENESIS. Angiogenesis is the process by which new blood vessels form in tissues and organs. Physiological: The process of regeneration Scar formation Sewerage of blood clots and other damage Angiogenesis is also active during the period of growth and development of the organism. In other cases, the intensity of angiogenesis is moderate.

In other cases, active angiogenesis is noted in pathological conditions of the body, in particular, in oncological processes. The tumor grows only due to the fact that it creates its own network of capillaries, through which all the necessary nutritional components are delivered to the neoplasm.

A newly formed malignant tumor in the human body is devoid of blood vessels, the neoplasm is nourished by diffusion. Feeding the tumor in a diffuse way is possible only if its size is small (approximately 1-2 cubic millimeters). After a network of microvessels begins to form in the tumor, the neoplasm actively progresses. There is an infiltration of the tumor into neighboring tissues and its further spread.

Tumor vessels differ from other vessels in their immaturity, as well as the possible presence of pores - the so-called vascular holes, due to which tissue edema and the release of tumor cells and other mediators outside the tumor into the tissue space can occur. The permeability of tumor vessels, as well as their high density, greatly facilitate the process of metastasis.

PROGRESSION AND HETEROGENEITY OF TUMORS. Progression is a change in the totality of tumor signs (genotype, karyotype and phenotype of tumor cells, which includes various features of their morphological, biochemical and other differentiation) in the direction of increasing malignancy. Differences are expressed by: Invasiveness New growth rate Ability to metastasize New karyotype Change in sensitivity to hormones and anticancer drugs Tumor progression and associated heterogeneity are the result of multiple mutations. Which gives rise to new subclones with new and different features.

STAGE OF NON-INVASIVE TUMOR Progression of dysplasia is associated with additional effects leading to subsequent genetic rearrangements and malignant transformation. As a result, a malignant cell appears, which divides for some time, forming a node (clone) of similar cells, feeding on the diffusion of nutrients from the tissue fluid of adjacent normal cells. tissues and not germinating in them.

STAGE OF INVASIVE TUMOR The stage of invasive tumor is characterized by the appearance of infiltrating growth. A developed vascular network appears in the tumor, the stroma is expressed to varying degrees, the borders with the adjacent non-tumor tissue are absent due to the germination of tumor cells into it.

Tumor invasion proceeds in four phases and is provided by certain rearrangements: loss of intercellular contacts, attachment to the components of the extracellular matrix, degradation of the extracellular matrix, migration of the tumor cell.

The first phase of tumor invasion is characterized by weakening of contacts between cells. On the cell surface, the concentration of calcium ions decreases, which leads to an increase in the negative charge of tumor cells. The expression of integrin receptors, which provide attachment of the cell to the components of the extracellular matrix - laminin, fibronectin, and collagens, is enhanced.

In the second phase, the tumor cell secretes proteolytic enzymes and their activators, which ensure the degradation of the extracellular matrix, clearing the way for invasion. At the same time, the degradation products of fibronectin and laminin are chemoattractants for tumor cells that migrate to the degradation zone during the third phase of invasion, and then the process is repeated again.

METASTASIS. the final stage of tumor morphogenesis, accompanied by certain geno- and phenotypic rearrangements. The process of metastasis is associated with the spread of tumor cells from the primary tumor to other organs through the lymphatic, blood vessels, perineural and implantation.

WAYS OF METASTASIS Lymphogenic way of tumor metastasis (with lymph flow through lymphatic vessels). This is the most common route for tumor metastasis. Hematogenous pathway of tumor metastasis (with blood flow through the blood vessels). Tissue or implantation pathway of tumor metastasis. Metastasis in this way is carried out when the tumor cell comes into contact with the surface of normal tissue or. Quite often, tumors metastasize through several pathways simultaneously or sequentially.

Clinical oncology includes many diseases that differ significantly in their course, prognosis, and treatment methods depending on the origin of the tumor, its histological form, localization, and other factors.

The progress achieved in recent years in biology is due to the extraordinary efforts that are being made by the world scientific community in the fight against malignant neoplasms. The causes of carcinogenesis are rooted deep in the very basis of life and are closely intertwined with such fundamental concepts as cell division, intercellular interactions, death, aging and immortality. Only in the last quarter of the XX century. there were real prerequisites for solving the problem of malignant neoplasms. The main ones are the deciphering of the structure, function and regulation of the gene, the further development of genetic and cell engineering, and especially the computerization of scientific research.

The progress achieved due to this is comparable in scale and significance to the scientific revolutions of the early 20th century. in physics. The scientific revolution in biology that is taking place before our very eyes is far from over. At the beginning of this century, it is planned to complete the Human Genome project, which is aimed at deciphering all the nucleotide sequences of human DNA in order to penetrate into the essence of the genetic programs that control the life of a cell and an organism.

The intensity of research in this area and their specialization is extremely high. This chapter provides only the most important information about tumor growth.

A tumor (neoplasm, blastoma, neoplasm) is a pathological growth that differs from other pathological growths (hyperplasia, hypertrophy, regeneration after injury) by a hereditarily fixed ability for unlimited, uncontrolled growth.

There are two main types of tumors - benign and malignant.

benign tumors.

Such tumors grow, pushing apart adjacent tissues, sometimes squeezing them, but usually without damaging them; in some cases they are encapsulated. Benign tumors, as a rule, do not have an adverse effect on the body, so they can be considered as local growths that do not interfere with the administration of vital functions. Their clinical significance is small. The only exceptions are those cases when the localization of the tumor itself is a factor that threatens the life of the organism, for example, when it occurs in the brain and compression of the nerve centers as a result.

Malignant tumors.

This is a large group of severe, chronic diseases, ending, as a rule, in a fatal outcome, if there was no or late medical care. Malignant tumors are characterized by invasive growth, they infiltrate adjacent tissues, form perifocal foci of inflammation, often metastasize to nearby lymph nodes and distant tissues, and have a generalized effect on the entire body, upsetting its homeostasis. All subsequent presentation is devoted to the description of this type of tumors.

Histological types of tumors.

The human body consists of about 100 different types of cells, and almost all of them can transform into tumor cells. Depending on the type of transformed cells, tumors are divided into cancer (originate from epithelial cells) and sarcomas (originate from connective tissue cells). Since the former occur about 10 times more often than the latter, the term "cancer" is often used to refer to all malignant neoplasms. However, due to the ubiquitous presence of connective tissue elements in the body, sarcomas can appear in almost any organ or tissue. The localization and histological type of a tumor largely determine its growth rate, sensitivity to certain therapeutic effects, the ability to metastasize and relapse, and ultimately clinical course and prognosis. Therefore, the histological diagnosis of the tumor is of paramount importance for the choice of treatment strategy.

There are many forms of cancer, for example, adenocarcinoma (glandular cancer - arises from the epithelium of the glands), papillary cancer (forms papillary structures), bronchiolo-alveolar (from the epithelium of the bronchi), squamous cell cancer, signet cell, oat cell, small cell, giant cell (in the form of forming their cells), medullary cancer (by external resemblance to brain tissue), skirr (“solid” cancer with a predominance of stromal elements), epidermoid cancer (by resemblance to stratified squamous epithelium of the skin), etc.

Sarcomas are subdivided (according to their localization) into sarcomas of bones, soft tissues and organs, and according to the type of initial cells - into fibrosarcomas, liposarcomas, leiomyosarcomas and rhabdosarcomas (come from muscle elements), as well as lymphosarcomas, chondrosarcomas, etc.

Prevalence. Tumor diseases affecting all representatives of the animal world are so widespread that they are the second cause of death after cardiovascular diseases. In the modern world, approximately one in four people is faced with oncological pathology, and one in five die for this reason. For an infant born in Russia in 1992, the probability of developing a malignant neoplasm during the coming life is 19.6% for a boy and 16.0% for a girl, and the probability of dying from this pathology is 16.5% for a boy and 10. 8% for a girl. The number of oncological diseases is growing, which is explained by both the general aging of the population and the increase in the influence of carcinogenic factors. Increasingly, malignant tumors occur in childhood and infancy.

Risk factors contributing to tumor development.

These factors, commonly referred to as risk factors, are divided into three main groups: bad habits, poor working conditions, and environmental pollution. The most common bad habit is smoking, which is the cause of 90% of lung cancer cases, especially in men, and less often - the cause of other forms of tumors: stomach, mouth, pharynx and liver. The risk of developing malignant neoplasms increases in people who eat a diet rich in animal fats and smoked foods that are low in fiber. A very important role is played by the high concentration of nitrates and pesticides in food and water, which dramatically increase the risk of developing tumors. Conversely, vitamins C, A, β-carotene, especially in vegetables and fruits, have a protective effect. Excessive sun exposure increases the risk of melanoma. Up to 4 °C of malignant neoplasms is associated with professional activity. In 1897, scrotum cancer was first described in chimney sweeps in London. The list of harmful industries is growing, including the production of aniline dyes, asbestos, asphalt, insecticides, pharmaceuticals, etc. More than 100 substances produced by man are carcinogenic. These substances, together with industrial wastes, pollute water bodies and the atmosphere: they are part of building materials and get into food. Radioactive compounds also play an important role. In recent years, the role of various factors in the development of malignant neoplasms has been intensively studied. According to the scientific literature, 30% of all cancer cases are associated with smoking, 3% with alcohol, 35% with unhealthy diet, 5% with occupational hazards. including industrial waste.

genetic predisposition.

A clear genetic predisposition to tumors in the so-called "cancer families" occurs in 5-10% of cases of malignant neoplasms. The highest incidence of malignant tumors (up to 100%) and the relatively early age of patients associated with family relationships occur with hereditary diseases. These include: Li-Fraumeni, Gardner and Bloom syndromes, xeroderma pigmentosum, Fanconi anemia, familial intestinal polyposis, ataxia-heleangiectasia and many others. Significant progress in understanding the role of heredity in the origin of a malignant tumor is associated with the completion of the Human Genome Project. The sequence of three billion nucleotides that make up the chromosomal DNA of a human cell has been deciphered almost completely. This is one of the significant achievements of the past century. At the same time, the scientific progress being made before our eyes is far from complete. In particular, a lot of time will be required in order to extract their functional content from the deciphered genetic texts. To a certain extent, the depth of our knowledge of the normal structure of the cell and the mechanisms of its malignant transformation depends on this. In the structure of the general incidence, cancer in the maxillofacial region is 32.5% (N. N. Trapeznikov et al., 1997; A. I. Paches, 1997). Cancer of the lower lip is 3 - 8%, cancer of the tongue - about 55%. cheeks - 12 - 15%, floor of the mouth - 10-12%, alveolar processes of the upper jaw and hard palate - 5-6%, alveolar process of the lower jaw - 5 - 6%, soft palate - 6 - 7% (P. G Bityutsky et al., 1996).

Cancer of the oral cavity among tumors of the head and neck ranks second after cancer of the larynx and develops 5-7 times more often in men than in women. Predisposing factors for the occurrence of cancer of the lips and organs of the oral cavity are adverse environmental and atmospheric effects and, apparently, aggravated heredity. Chronic mechanical injuries and irritations, smoking, atrophy of the integumentary epithelium in old age, alcohol abuse also contribute to the appearance of precancerous diseases. The most common precancerous disease of the vermilion border of the lip is Manganotti's cheilitis (34.9%) and limited hyperkeratosis (25.5%). As for the precancerous lesions of the oral mucosa, the tongue mucosa is affected more often by leukoplakia in various variants (38.3%). The same applies to the mucous membrane of the floor of the oral cavity, but the frequency of lesions in this case was significantly higher in comparison with lesions of other organs and amounted to (57%). It was noted that cancer of the lip and oral mucosa occurs much more often in men (81.1%) than in women (18.9%). The age of patients ranges on average from 51 to 70 years with a tendency to develop lesions at a younger age.

Prevention

The development of any oncological disease is associated both with the influence of environmental factors and with the characteristics of the organism itself. Fortunately, a hereditary predisposition to oncological diseases is a relatively rare phenomenon and it does not guarantee the mandatory development of a tumor, especially if the basic principles of prevention are observed.

Who is most at risk of getting sick? How to reduce the risk? To answer these questions, it is necessary to remember which tumors are the most common, what factors cause the maximum risk of their development. If we take the entire incidence of cancer, then the first place among the main causes is malnutrition (35% of tumors), and the second place belongs to smoking (30%). That is, 2 cases of cancer out of three are due to these factors. Next, in decreasing order of importance, are viral infections, ionizing and ultraviolet radiation, a sedentary lifestyle, occupational carcinogens, sexual factors, alcoholism, and polluted air.

^ Dietary principles that help reduce the risk of developing cancer

1. Prevention of obesity. In experiments, it has been shown that the consumption of more high-calorie foods leads to an increase in the incidence of tumors. There are many explanations, and far from last is “metabolic immunosuppression”. And further. The incidence of some malignant tumors is inversely proportional to physical activity, which, among other things, leads to the expenditure of calories.

2.Reduce dietary fat intake..

3.Inclusion in the daily diet of fresh vegetables and fruits

4. Consumption of food enriched with fiber, pectins - whole grains of cereals, vegetables and fruits

5. Limiting the consumption of alcoholic beverages.

6. Limiting the consumption of smoked and nitrite-containing foods.

smoking and cancer

It's no secret that smoking accounts for at least 80% of lung cancer cases. But not everyone knows that smoking also contributes to the development of cancer of the entire gastrointestinal tract, breast and other organs. The reason is simple - chemical and physical carcinogenic factors most intensively affect the smoker's lungs, but they can enter the gastrointestinal tract with sputum and saliva and affect the entire body. Each pack of cigarettes gives a dose of radiation exposure of at least 8 microsieverts, which is commensurate with the dose from one image on a digital fluorograph. As for the remaining factors, the recommendations are obvious: it is necessary to strengthen the immune system, lead an active lifestyle, sunbathe less in the sun (15 minutes a day is enough). The implementation of these simple rules will reduce the risk of developing tumors by about 10 times.

^ Prevention of diseases of the mammary glands. Breast cancer is the most common disease, ranking first in prevalence among all malignant diseases.

Ways to detect breast cancer: self-examination - 85%, medical examinations - 10%.

BREAST SELF-EXAMINATION METHOD

Breast cancer refers to visual localizations, it is possible for a woman to detect tumors on her own during self-examination: if a woman is menstruating, then an examination of the mammary glands should be carried out once a month after 7-10 days from the onset of menstruation, when soreness and swelling of the breast disappear. In menopause, an examination should be carried out once a month at any time when there is no breast engorgement.

7.4. risk factors for tumor growth

Aging. Every person, either from birth or from childhood or adolescence, is a carrier of a tumor. We are talking primarily about completely benign nevi, birthmarks, and other nodules in the skin. With aging, the number of nevi may increase, sometimes there are basal cell papillomas, senile warts of the skin. After 55 years, a person enters a period when the likelihood of a malignant neoplasm progressively increases every year. Most cases of death from malignant tumors are noted in the age range from 55 to 74 years.

Influence of geographical zones and environmental factors.

There are significant geographic differences in rates of morbidity and mortality from malignant tumors. For example, mortality from stomach cancer in Japan is 7-8 times higher than in the US, and from lung cancer, on the contrary, is 2 times higher in the US than in Japan. Compared to Iceland, skin melanomas are 6 times more common and cause death in New Zealand. Most modern experts believe that there is no specific racial predisposition to certain tumors. This is confirmed by long-term comparative studies of the corresponding indicators in indigenous people and emigrants, representatives of the same race.

The very important and often manifested role of ultraviolet rays (solar radiation) in carcinogenesis will be discussed in this chapter, and the influence of occupational factors will be discussed in Chapter 9. excesses, traditions, peculiarities in nutrition and behavior. For example, excess body weight by 25% of the average constitutional norm is considered an important risk factor for the development of colon and genital cancer. Constant smoking of filter cigarettes actually increases the incidence of lung cancer (77% of men with this form of cancer are smokers), as well as cancer of the larynx, pharynx, esophagus, oral cavity, pancreas and bladder. Chronic alcoholism is a powerful risk factor for malignancy in the oropharyngeal zone, larynx, esophagus, and also in the liver (often based on cirrhosis).

Heredity. Studies show that the death rate from lung cancer among non-smoking immediate relatives of persons who died from this particular disease is 4 times higher than among non-smoking relatives of people who died from other diseases. All inherited forms of malignant neoplasms can be divided into 3 groups: hereditary syndromes of a malignant tumor; familial forms of neoplasia; autosomal recessive syndromes of DNA repair disorders. Let's look briefly at each group.

A group of hereditary tumor syndromes. Includes known neoplasms, in which the inheritance of a single mutant gene greatly increases the risk of their development. This predisposition refers to an autosomal dominant type of inheritance. The most common example is retinoblastoma (malignant neuroepithelioma of the retina) in children. The probability of this tumor, often bilateral, in carriers of this gene is 10,000 times higher than in normal children. It has been noted that such carriers have a tendency to form a second tumor, in particular osteosarcoma. Another example is hereditary adenomatous polyposis of the colon, which develops shortly after birth. If children with this disease survive, grow up and live up to 50 years, then in 100% of cases they develop colon cancer. There are several features that characterize this group of syndromes.

In each of the syndromes, the tumor process affects a certain organ and tissue localization. So, the 2nd type of syndrome of multiple endocrine neoplasia concerns the thyroid gland, parathyroid glands and adrenal glands. It has no predisposition to other tumors. Within this group, tumors often have a characteristic phenotype. For example, there may be a large number of benign nodules (colon polyposis) in the affected tissue, or in neurofibromatosis type 1 (see Chapter 8), multiple pigmented spots on the skin (colon with milk) may appear, as well as Lisch nodules (A. Lisch), which are pigmented hamartomas in the iris. As with other autosomal dominant diseases, there is incomplete penetrance (frequency or likelihood of gene expression) and variable expressivity (degree of development of the trait).

Familial forms of neoplasia. In fact, all common types of malignant tumors that occur sporadically are also observed as familial forms. These are carcinomas of the intestine, breast, ovaries and brain tumors. Common signs of familial neoplasm are early onset, occurrence in at least two or more immediate family members, and frequent bilateral or multiple lesions. Family forms have neither a characteristic phenotype nor specific dynamics. For example, unlike malignancy in hereditary adenomatous polyposis of the colon, the familial form of cancer of this organ does not develop from a previous glandular polyp.

Autosomal recessive syndromes of impaired DNA repair (autosomal - the same as chromosomal, except for sex chromosomes, and recessive - manifested in the phenotype). We are talking about the instability of the structure of DNA or chromosomes. The group of these syndromes includes xeroderma pigmentosa (pigmentation, hyperkeratosis, edema and other skin changes during sun exposure), Fanconi anemia, characterized by bone marrow hypoplasia, low blood cell count, and many anomalies.

In general, 5 to 10% of human malignant tumors are associated with a hereditary predisposition. The term hereditary, not genetic, should be used, since the latter concept refers to the genetic apparatus that controls not only the transmission of hereditary traits, but also performs broader functions.

The role of chronic proliferative changes. The basis of malignancy are metabolic, dyshormonal, and chronic inflammatory processes. Bronchogenic cancer is often preceded by focal hyperplasia, metaplasia and dysplasia of the bronchial epithelium, which occur in smokers under the influence of carcinogenic products on the metabolism of epitheliocytes. Hyperplasia, dysplasia, as well as differentiation disorders in the lining of the vaginal portion of the cervix, which have a dyshormonal nature, can also be associated with the development of cancer. Chronic stomach ulcers, cirrhosis of the liver and other inflammatory and destructive processes of a protracted nature in many cases are fraught with the same danger.

All these processes are classified as facultative precancerous changes and are often referred to as "precancer". Conditionally, some benign epitheliomas can also be attributed to the concept of facultative precancer. For example, a growing villous adenoma of the colon is capable of malignancy in 50% of patients, and transitional cell papilloma of the bladder in 60%.

In chronic proliferative processes of a metabolic, dyshormonal or inflammatory nature, various interstitial causes through various mechanisms affect the genetic control over cell proliferation and differentiation.