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УДК: 613.6: 614.8
ПЕРСаН1Ф1КОВАНА МЕДИЦИНА ЯК ОСНОВА ПРОФ1ЛАКТИКИ ПРОФЕС1ЙНИХ ЗАХВОРЮВАНЬ
П'ятниця-Горпинченко Н.К.
PERSONALIZED MEDICINE AS A BASIS FOR OCCUPATIONAL DISEASES PREVENTION
ccording to the Human Rights Declaration, adopted in 1948 by the United Nations General Assembly, everyone has the right to decent working conditions. Prevention and preservation of the health of the working-age population is one of the priority issues of national health in many countries of the world. Every year 6-8 thousands occupational diseases are registered in Ukraine. Working in various sectors of domestic production and this is every fourth employee (21.7%), are exposed to about 140 harmful factors that exceed the maximum permissible levels, which is associated with the risk of forming an occupational and production-related pathology [1-4].
This is due to many objective reasons: the rapid pace of development of modern production, the emergence of new production factors (types of materials, energy), changes in the ownership of most industries and the lack of effective measures to influence the employer in terms of improving working conditions, the inability to generally achieve such working conditions that a priori could be
PIATNYTSIA-GORPYNCHENKO N.K.
Taras Shevchenko National University of Kyiv, Ukraine
https://doi.org/10.32402/dovkil2020.02.064
considered safe, the reform of the sanitary and epidemiological surveillance service in Ukraine [1, 5].
It should be noted that the EU strategy on health and safety at work (2014-2020) highlighted the important role of new and emerging risks, as well as new occupational and work-related diseases. Among the new physical and emerging risks, the role of physical exertion in the development of musculoskeletal disorders, risks from noise, vibration, thermal factors, ionizing radiation, machinery, lack of physical activity, combined effects of physical and psychosocial loads, multifactorial risks and biological new risks (antimicrobial and resistant strains of microorganisms, endotoxins, mold in the workplace, solid waste), etc. In this regard, currently, priority is given to the development of a personalized approach in occupational medicine in order to early detection, diagnostics, and prevention of the transition of a pathological process to a chronic form using the latest achievements of molecular biology, genetics, and information technology. The search for modern and affordable means of occupational and production-related pathology prevention, especially in the context of reforming the health care system in Ukraine gains ground [6-11].
In recent years, foreign experts in the field of health care actively develop a new direction of prevention and
PERSONALIZED MEDICINE AS A BASIS FOR OCCUPATIONAL DISEASES PREVENTION Piatnytsia-Horpynchenko N.K.
Kyiv Taras Shevchenko National University, Ukraine
Objective: We summarized the results of published research papers related to the development of the main areas of personalized medicine in health care practice, including occupational medicine and defined the prior issues that dictate the need for further study.
Materials and methods: We performed the analysis of literary data on the use of personalized medicine for the prevention of the occupational diseases.
Results: The personalized medicine was established to be a relatively new promising direction for the further development of medical science, its main task is to create an optimum model of the health care system in order to preserve the health of the working-age population. At the present stage of scientific and technological progress development, the crucial in the implementation of the basic principles of personalized medicine (prognostic, personalized, preventive and partner), as an integrative modeling system, is given to the development of information support and molecular genetic methods for the study of public health for the purpose of early detection, prevention and treatment of diseases. Conclusions: Despite the prospect of using the concept of personalized medicine in the health
care system, the domestic information and organizational, regulatory and legal (medical in some cases) base is significantly behind the needs of modern times, which makes it difficult to implement this direction in practice. However, over many years of scientific research in domestic occupational medicine, a fundamental basis has been formed for the further development of the personalized approach to the prevention of health disorders among workers. Nowadays some progress is being observed in the field of the search for biomarkers for early diagnosis and prevention of the formation of chronic occupational and work-related pathology, the Register of the Occupational Diseases of Ukraine has been substantiated, the methodology for the assessment and management of occupational risks is being improved, in particular, quantitative assessment of the potential and real danger of work-related exposure which is the basis for the real prevention of occupational pathology as a part of individual approach to the patient. Taking into account the current realities, the solution of the problem of the health preservation in the working requires a comprehensive approach with the involvement of the specialists in various fields: hygienists, occupational therapists, medical geneticists, specialists in the field of information technology, health care organizers.
Keywords: personalized medicine, biomarkers, information technologies, occupational risk.
© П'ятниця-Горпинченко Н.К. СТАТТЯ, 2020.
treatment of diseases - a patient-oriented approach. The founder of this idea is considered to be an American scientist L. Holland, who proposed to integrate the complex of various features of the body (metabolic, constitutional, etc.) with fundamental methods of differential diagnosis of diseases when evaluating the clinical status of patients with various pathologies. This concept was further developed, as a result of which in 1998 another American scientist, K. Jane, justified the need for such a systematic approach in the clinic of internal diseases and was first who introduced the term «personalized medicine». At the beginning of formation and development of personalized medicine, this concept was considered in the context of the symbiosis of genetic science and clinical medicine. Today, some researchers identify the term «personalized medicine» with the concept of «genomic medicine», which involves the use of information about genomes (human and other organisms) and their derivatives (RNA, proteins, metabolic products) in order to implement certain medical solutions. As the analysis of foreign literature shows, personalized (predicative, preventive) medicine is a broader concept and combines various approaches aimed at improving the health of the population (for example, non-genomic personalized screening to identify risk groups for diseases), including occupational medicine [2, 3, 13-17].
According to modern concepts, personalized medicine is understood as a special model of health care based on prognostic, personalized, preventive and partner principles («P4 medicine») and is closely related to modern biomedical information technologies. Recent publications emphasize that there are three areas of personalized medicine: prevention, diagnosis, and treatment of diseases [14, 16, 18].
It should be noted that the decoding of the human genome opened a new era of biomedicine, which radically changed the vector of further development of medical science towards a deeper understanding of the pathogenesis of various diseases at the molecular level [19]. Taking into account the increasing role of molecular data in the prevention, prognosis and treatment of difficult diseases that are characterized by clinical heterogeneity (for example, cancer), the search for specific biomarkers of the disease - biological «indicator»
compounds that indicate the presence of a specific disorder in the body or a tendency to develop it is of paramount importance in the modern personalized approach to the patient. Today, medical practice uses biomarkers that act at the level of cells and subcellular structures. It is predicted that markers at the genome, transcriptome, proteome, and metabolome levels will be available for use in the near future. This revolutionary approach marked the beginning of the development of «omics-based medicine», the main goal of which is to create a more individual medicine with an emphasis on the preventive direction. The use of various molecular tools in clinical practice - «omics-derived molecular tools» (for example, siRNA, ribozymes) is intended to help to create a more complete picture of the nature of the disease, determine a set of specific markers for the prevention of the disease, make a personalized diagnosis and select the optimal management tactics for the patient. In practice, this is implemented in the development of test systems that help to more accurately determine the state of human health, improve the diagnosis of the disease in the case of its latent (subclinical) course, determine the degree of progression of the pathological process or predict the individual response of the patient to pharmacotherapy [12, 16, 19]. For example, based on the analysis of nucleic acids by amplification using low-density microchips, their pilot samples were developed to study disorders in certain genes (for example, CDKN2A, SFRP1) associated with cancer. This approach is also successfully used to identify risk groups for occupational pathology. For example, there are data from molecular genetic studies in occupational medicine on the relationship of certain genotypes (for example, XPD*Asn/Asn genotype) with the risk of bronchopulmonary pathology development in a population of workers who come into contact with industrial hazards
omflfl n ITEPATyPM =
(dust of primarily fibrogenic action), concerning molecular genetic features of the formation of occupational asthma [2, 3, 7, 15-17]. However, the development of methods for early diagnosis and prevention of diseases, including at the molecular genetic level is complicated when it comes to some multifactorial diseases that reflect the total influence of different genes and their interaction with environmental factors [1, 9, 14, 20-23].
Speaking about personalized treatment, it should be noted that according to experts of the World Health Organization, 40% of patients (with the standard approach) can not achieve the expected effectiveness of therapy. Therefore, at present, the emphasis shifts from mass therapy to targeted therapy. Individual approach to the patient allows to determine the optimal treatment, taking this into consideration his/her genetic characteristics, which is desirable not only from a medical point of view, resulting in a minimized risk of unwanted side effects and improve quality of treatment, but also economic[12, 16, 24]. Research in this area is aimed at identifying polymorphisms (differences) of the leading genes that determine the tactics of treatment of various diseases, clarifying the mechanisms of action of pharmacological drugs, searching for alternative factors that affect the effectiveness of therapy, which will determine new clinically significant prognostic markers of treatment effectiveness, and developing new treatment methods (for example, based on tautologies stem cells). Foreign authors note the main features of personalized medicine (molecular) - an individual approach to the patient and precautionary orientation. The latter allows to completely prevent the disease development. Finding out the gene network of each multifactorial disease, identifying the central genes and modifier genes in it, analyzing the association of
their alleles with the disease, and a set of preventive measures development for a specific patient on this basis form the basis of predictive medicine. As a result, information can be obtained about a particular degree of risk of developing diseases and a pathogenet-ically based management tactic can be developed [22-27].
One of the promising areas for the development of personalized prevention is the development of individual genetic maps with the determination of a person's genetic predisposition to various diseases (especially socially significant ones), identification of carriers of mutations of frequently occurring monogenic and dominant diseases that differ in late onset (diabetes, hereditary forms of breast cancer). This aspect of personalized medicine reflects the definition of individual human sensitivity to the damaging effects of various harmful factors of the production and environment (ionizing radiation, chemical and biological agents, including viruses). This will allow us to develop and recommend specific preventive measures - dispensary observation, application of appropriate screening and diagnostic methods for the early diagnosis and treatment of diseases. From the point of view of occupational medicine, this approach is also applicable for rational selection of candidates for the profession in order to reduce the risk of a number of occupational and work-related diseases (for example, occupational cancer) [6, 7, 12, 28, 29].
In occupational medicine, modern molecular technologies are becoming increasingly important and are used to assess the risk of developing occupational diseases and the most common forms of non-infectious diseases in order to identify early (preclinical) health disorders of workers in harmful and dangerous working conditions, as well as to diagnose and evaluate the effectiveness of treatment. From the point of view of information content and diagnostic significance from the position of breadth of assessment of the metabolic status of a person, molecular diagnostics dominates in many sections of clinical medicine, including diagnosis and treatment of occupational diseases [2-4, 6, 7, 22].
The preventive vector of personalized medicine also involves screening the population and stratifying individuals at high risk of the disease development by
establishing a link between their molecular profile (for example, gene expression, genetic variations) and the disease phenotype. According to experts, this direction dictates the need for a detailed study of the composition, distribution and function of key molecules involved in the pathogenesis of the disease.In addition, for effective disease prevention, personalized approach involves the development of special mathematical models to determine the interdependence between some risk factors (e.g., detection of comorbidi-ties that increase the risk of developing other diseases) and disease activity by means of the mechanistic approach [12, 19, 20].
Since personalized medicine is a relatively new area that requires reforming the health care system, foreign experience indicates a number of difficulties that make it difficult to implement it everywhere. One of the important tasks in the implementation of the predicative approach concept is to resolve the bioinformatic aspects of the problem of introducing personalized medicine into healthcare practice, and the methods of collecting and processing electronic medical information unification. Further development of health care on the platform of personalized medicine dictates the need to improve the functioning of the system as a whole in order to effectively implement each of its specific areas: prognostic, personalized, preventive and partner as an integrative modeling system. In the future, a number of issues of a social and legal, economic and ethical nature will have to be solved - the implementation of special training programs for specialists, the development of new qualification requirements for genetics consultants, compensation for moral damage to the patient due to the likelihood of false-positive results of the study with the ensuing consequences in the form of inappropriate treatment and excessive healthcare costs; development of protocols to ensure that the doctor makes the right decisions in a given clinical situation [13, 14, 18].
It should be noted that due to many reasons, the personalized approach did not go any further neither in the health care system of Ukraine nor in the post-Soviet countries. In domestic scientific literature, «personalized medicine» term is almost not found. Nevertheless, there are good reasons to believe that the achieve-
ments of cell and molecular biology will form the basis for the further development of personalized medicine, especially its preventive and prognostic directions [16, 29, 30]. For example, for many years, domestic and foreign specialists in the field of occupational pathology have been conducting fundamental research on the clinical significance of various genetic markers for screening in the profession, including determining the susceptibility or resistance to the influence of a harmful production factor, early diagnosis of occupational diseases, and developing a conceptual basis for creating a Register of occupational diseases. Preventive medicine also reflects the ideology of health risk assessment and management, including the characterization of individual risks in specific occupational groups, which has been widely used in occupational medicine since the 1970s. This prevention won international acclaim and is based on hazard harmful and dangerous production factors identification, assessing their impact and determining quantitative parameters characterizing the effect of leading harmful factors. Despite the fact that today there are many occupational risk assessment models depending on the prevailing adverse industrial impact, most of them are in the plane of determining/predicting the «dose-effective-time» relationship between the influence of a harmful factor and occupational pathology. It should be noted that most experts agree that there is no unified occupational health risk assessment scheme, which dictates the need to improve the individual health risk assessment of workers in the framework of personalized medicine, taking into account the concepts of WHO, ILO and the principles of evidence based medicine [2, 3, 6, 7, 9].
Certain difficulties are also associated with the harmonization of terminology relating to the definition of the concept of «occupa-tional» or «production-related disease», the inclusion of a particular pathology in the list of such pathologies, as well as methods for establishing, measuring and controlling harmful production factors. This is due to the fact that in some cases, this relationship may be unstable or weakly expressed, difficult to identify, as well as methodological and organizational difficulties, which makes it difficult to accurately assess them, and therefore establish a
ПЕРСОН1Ф1КОВАНА МЕДИЦИНА ЯК ОСНОВА ПРОФ1ЛАКТИКИ ПРОФЕС1ЙНИХ ЗАХВОРЮВАНЬ П'ятниця-Горпинченко Н.К.
Кивський нацональний ушверситет iм. Тараса Шевченка, м. Кив, Украша
Мета. Узагальнення результата опублкованих наукових робт, що стосуються розвитку основ-них напрямюв персонiфiкованоí медицини у практиц охорони здоров'я, у тому числ'1 медицина праш; визначення проритетних питань, як диктують необхщнють подальшого вивчення. Матер!али та методи. Проведено анал'\з даних лтератури щодо використання персонал'зовано! медицини для профлактики профе^йних захво-рювань.
Результати. Встановлено, що персонiфiкована медицина - вдносно новий перспективний напрямок подальшого розвитку медичноI науки, основним завданням яко1 е створення оптимальноI модел '1 системи охорони здоров 'я з метою збереження здоров'я працездатного населення. На сучасному ^ етап розвитку науково-техн'1чного прогресу вирiшальне значення у реал'1зацп основних принципiв персонiфiкованоí медицини (прогностичний, персонiфiкований, профлак-тичний \ партнерський) як системи нтегративно-го моделювання выводиться розробц iнформа-шйного забезпечення та молекулярно-генетич-них методв вивчення здоров 'я населення з метою раннього виявлення, профлактики та л'\кування захворювань.
Висновки. Незважаючи на перспективнсть застосування концепци персонiфiкованоí медицини у систем\ охорони здоров 'я втчизняна нфор-мацйно-оргашзацйна, нормативно-правова (у деяких випадках - медична) база стотно вдстае вд потреб сучасност'1, що ускладнюе впроваджен-ня цього напрямку у практику. Проте у в 'тизнянй медицин прац за багато роюв наукового пошуку сформувалася фундаментальна основа для подальшого розвитку персонiфiкованого п'1дходу для попередження порушень здоров'я пращвни-юв. Вже нин певнi усп 'ки спостергаються у галуз'1 пошуку бюмаркерiв ранньоI дагностики та профi-лактики формування хронiчно'¡ професйноI та виробничо-зумовленоI патологи, обфунтоване створення Реестру професйних захворювань Украни, удосконалюеться методолопя оцнки та управлння професйним ризиком, зокрема кль-к'юна о^нка потенцйноI та реальноI небезпеки впливу шюдливих виробничих фактор'в, що е основою реальноI профлактики професйноI патологи у рамках ндивдуального п'щходу до патента. З урахуванням реалй сьогодення виршення проблеми збереження здоров'я пращвниюв вима-гае комплексного п'1дходу з залученням фаювшв рiзного профлю - ппенюш, профпатолопв, медичних генетиюв, фашщв у галуз '1 нформащй-них технолопй, органiзаторiв охорони здоров'я.
Ключовi слова: персонфкована медицина, б'юмаркери, 1нформац!йн1 технологи, професйний ризик.
relationship with the identified disease. It is necessary to take into account that the state of human health depends on the complex impact of many other industrial and non-industrial factors (environment, life style, bad habits), so there is a possibility of underestimating their impact. Today, the prognostic and preventive direction of personalized medicine can find the appropriate point of application in occupational medicine. Occupational safety and health have a strong basis for further development, using approaches at both the population and individual levels. if necessary, it is possible to switch from personalized medicine to personalization of the entire system of labor protection [1, 5, 7, 22].
Thus, the postulate of the outstanding scientist and teacher, founder of topographic anatomy N. Pirogov that «The future belongs to preventive medicine» is embodied at a new level with the use of innovative biomedical technologies. This integrated approach will solve many problems related to the adverse impact of factors of production and environment on human health. At the same time, medicine focuses on each patient, and is primarily preventive in nature, optimizing the reserve capabilities of a person and pro-
longing his/her active longevity, thereby reaching a qualitatively different level of medical care.
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ПЕРСОНИФИЦИРОВАННАЯ МЕДИЦИНА КАК ОСНОВА ПРОФИЛАКТИКИ ПРОФЕССИОНАЛЬНЫХ ЗАБОЛЕВАНИЙ Пятница-Горпинченко Н.К.
Киевский национальный университет им. Тараса Шевченко, г. Киев, Украина
Цель. Обобщение результатов опубликованных научных работ, касающихся развития основных направлений персонифицированной медицины в практике здравоохранения, включая медицину труда; определение приоритетных вопросов, диктующих необходимость дальнейшего изучения. Материалы и методы. Проведен анализ литературных данных по применению персонализированной медицины для профилактики профессиональных заболеваний. Результаты. Установлено, что персонифицированная медицина - относительно новое перспективное направление дальнейшего развития медицинской науки, основной задачей которой является создание оптимальной модели системы здравоохранения с целью сохранения здоровья трудоспособного населения. На современном этапе развития научно-технического прогресса решающее значение в реализации основних принципов персонифицированной медицины (прогностический, персонифицированный, профилактический и партнерский) как системы интегративного моделироания отводится разработке информационного обеспечения и молеку-лярно-генетических методов изучения здоровья населения с целью раннего выявления, профилактики заболеваний и лечения пациентов. Выводы. Несмотря на перспективность применения концепции персонифицированной меди-
цины в системе здравоохранения отечественная информационно-организационная, нормативно-правовая (в ряде случаев - медицинская) база существенно отстает от потребностей современности, что затрудняет внедрение этого направления в практику. Однако в отечественной медицине труда за многие годы научного поиска сформировалась фундаментальная основа для дальнейшего развития персонифицированного подхода для предупреждения нарушений здоровья работающих. Это обусловлено тем, что уже сегодня определенные успехи наблюдаются в области поиска биомаркеров ранней диагностики и профилактики формирования хронической профессиональной и производственно-обусловленной патологии, обосновано создание Реестра профессиональных заболеваний Украины, совершенствуется методология оценки и управления профессиональным риском, в частности количественная оценка потенциальной и реальной опасности воздействия вредных производственных факторов, что является основой реальной профилактики профессиональной патологии в рамках индивидуального подхода к пациенту. С учетом реалий сегодняшнего дня решение проблемы сохранения здоровья работающих требует комплексного подхода с привлечением специалистов различного профиля - гигиенистов, проф-патологов, медицинских генетиков, специалистов в области информационных технологий, организаторов здравоохранения.
Ключевые слова: персонифицированная медицина, биомаркеры, информационные технологии, профессиональный риск.
[Structure of the Occupational Morbidity of Workers of Certain Categories at the Enterprises of the City of Kyiv]. Liky Ukrainy plius. 2013 ; 1 : 42-45 (in Ukrainian).
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nykh haluzei promyslovosti Ukrainy [XPD Gene Polymorphism (RS799793) and Bronchopulmonary Pathology in the Workers of Harmful and Dangerous Industries of Ukraine]. Ukrainskyi zhurnal z problem medytsyny pratsi. 2018 ; 1 (54) : 61 -65 (in Ukrainian).
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Hagrnwna go pegaK^i 02.03.2020
УДК 614.7:618.111 -006 https://doi.org/10.32402/
dovkil2020.02.070
OVARIAN CANCER INCIDENCEAND EFFECT OF ENVIRONMENTAL CHEMICAL POLLUTION ON ITS FORMATION (ANALYSIS OF LITERARY DATA)
Chernychenko I.O., Balenko N.V., Lytvychenko O.M., Babii V.F., Hlavachek D.O., Kondratenko O.Ye.
ЗАХВОРШВАН1СТЬ НА РАК ЯСЧНИК1В I ВПЛИВ НА II ФОРМУВАННЯ Х1М1ЧНОГО ЗАБРУДНЕННЯ ДОВК1ЛЛЯ (АНАЛ1З ДАНИХ Л1ТЕРАТУРИ)
станшми десятирiччями особливу увагу мiжнародних iнституцiй (ВООЗ, ООН, Мiжнародного агентства з вив-чення раку - МАВР), науков^в та фахiвцiв привертае проблема захво-рюваностi на гормонозалежш злоякю-нi пухлини, такими, як рак молочноУ залози (РМЗ), ендометрiю (РЕМ) яеч-никiв (РЯ) у жЫок, рак передмiхуровоi залози (РПЗ), тестикулярний рак у чоловшв, а також рак щитоподiбноi залози [1-6].
Актуальнють i важливiсть щеУ про-блеми було вiдзначено у сптьнм доповiдi експертiв ВООЗ/ООН [1], спе^ально присвяченiй аналiзу стану наукових дослщжень з вивчення хiмiч-них сполук, як чинять шкiдливий вплив на ендокринну систему, так зва-них ендокринних дизрапторiв (ЕД). Як вказують експерти, це пов'язане з двома обставинами: з одного боку, тенден^ею до зростання частоти i поширеност гормонозалежних пух-лин, що спостерiгаeться протягом останнiх 40-50 роюв у р^зних краУнах свiту, а з шшого - стабiльним збть-шенням кiлькостi ЕД, якi все бтьше забруднюють середовище життеди
ЗАХВОРЮВАНСТЬ НА РАК Я6ЧНИК1ВI ВПЛИВ НА II ФОРМУВАННЯ Х1М1ЧНОГО ЗАБРУДНЕННЯ ДОВКЛЛЯ (АНАЛ1З ДАНИХЛ1ТЕРАТУРИ) Черниченко 1.О., Баленко Н.В, Литвиченко О.М., Бабй В.Ф., ГлавачекД.О., Кондратенко О.6.
ДУ «1нститут громадського здоров'я iM. О.М. Марзеева НАМН Украни», м. Кив, Укра1на
Обфунтування. Наразi рак яечникв (РЯ) е одним з частих злоя-ксних захворювань жiнок в усьому свт з тенденшею тривалого зростання та провдною причиною смерт вд пнеколопчних форм раку. Одним з iмовiрних чинниюв збльшення частоти захворюва-ност на РЯ е хiмiчнi забруднення довклля, у тому числ'1 речовини, як мають гормональнi властивост та шюдливо впливають на ендокринну систему, так зван «ендокриннi дизраптори» (ЕД). Мета. Проанал'зувати дан лтератури щодо захворюваност на РЯ та впливу на И формування хiмiчних забруднювач'в довклля. Результати. Проведений анал'\з лтератури св'щчить про вдносно невелику кльюсть досл'1джень, особливо епщемюлопчних, при-свячених вивченню впливу хiмiчних забруднювач 'в довклля на захворювашсть на РЯ. ЕпЩемолотно було доведено вплив на зростання захворюваност на РЯ не лише поширених ЕД (пол'1хло-рованих бiфенiлiв i пестицидв - атразину, д '(азинону, метоксихло-
© Черниченко 1.О., Баленко Н.В, Литвиченко О.М., Бабй В.Ф., Глава чек Д.О., Кондра тенко 0.6. СТАТТЯ, 2020.
ЧЕРНИЧЕНКО 1.О., БАЛЕНКО Н.В, ЛИТВИЧЕНКО О.М., БАБ1Й В.Ф., ГЛАВАЧЕК Д.О., КОНДРАТЕНКО о.е.
ДУ «1нститут громадського здоров'я iм. О.М. Марзеева НАМН УкраУни», м. КиУв, УкраУна
