problendoПроблемы ЭндокринологииProblems of Endocrinology0375-96602308-1430Endocrinology Research Centre10.14341/probl10070problendo-10070Research ArticleОбзорыReviewsМетаболизм эстрогенов, прижизненные нарушения процессов метилирования и рак молочной железыEstrogen metabolism, lifetime methylation disorders, and breast cancerhttps://orcid.org/0000-0001-8022-9291ЧагайНаталья БорисовнаChagayNatalia B.

д.м.н.

MD, PhD

chagaynb@gmail.comhttps://orcid.org/0000-0003-1316-5245МкртумянАшот МусаеловичMkrtumyanAshot M.

д.м.н., профессор

MD, PhD, Professor

vagrashot@mail.ru<p>Ставропольский краевой клинический консультативно-диагностический центр; Ставропольский государственный медицинский университет</p>Россия<p>Stavropol Regional Clinical Consultative and Diagnostic Center; Stavropol State Medical University</p>Russian Federation<p>Московский государственный медико-стоматологический университет им. А.И. Евдокимова</p>Россия<p>Moscow State University of Medicine and Dentistry named after A.I. Evdokimov</p>Russian Federation201912092019653161173Copyright &#x00A9; Чагай Н.Б., Мкртумян А.М., 20192019Чагай Н.Б., Мкртумян А.М.Chagay N.B., Mkrtumyan A.M.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.probl-endojournals.ru/jour/article/view/10070

Причиной запуска онкогенеза может быть повышение активности генов, ответственных за инициацию опухолевого роста в стволовых клетках или клетках-предшественниках, а также подавление функционирования генов-супрессоров. Воздействие эндогенных эстрогенов ассоциируется с повышенным риском рака молочной железы (РМЖ) у женщин как в пре-, так и в постменопаузе.

Важнейшим шагом в понимании патогенеза РМЖ явилась теория «переключения» эстрогенного эффекта с гормонального на генотоксический, согласно которой главными виновниками онкогенеза признаны не собственно метаболиты эстрогенов, а их производные, по повреждающим характеристикам соответствующие химическим проканцерогенам. Происхождение упомянутых веществ и формирование генотоксичности эстрогенов кроются в нарушении процесса инактивации катехолэстрогенов в реакциях метилирования.

Основной эпигенетической модификацией генома человека является метилирование молекул ДНК клетки. Метилирование ДНК не изменяет первичной последовательности нуклеотидов, но необходимо для функционального подавления определенных генов. Феномен гипометилирования-гиперметилирования лежит в основе долговременного сайленсинга различных генов, в том числе генов-супрессоров опухолевого роста.

Питание, образ жизни, сопряженный с потреблением сверхдопустимых количеств алкоголя, курением, определяют доступность метильных групп в организме и метаболизм эстрогенов, а также эпигенетические изменения ДНК генома. Актуальной представляется оценка индивидуального риска РМЖ на основе изучения экспрессии и метилирования гена СОМТ, ответственного за метаболизм эстрогенов.

Oncogenesis can be caused by an increase in the activity of genes responsible for initiating tumor growth in stem or progenitor cells, as well as a reduction in the functioning of suppressor genes. Endogenous estrogen exposure is associated with an increased risk of breast cancer in both pre- and postmenopausal women.

The most important step in the understanding of the pathogenesis of breast cancer was the development of the theory of the switching of estrogen’s effect from hormonal to genotoxic, in which the main culprits of carcinogenesis are not chemical metabolites of estrogens, but their derivatives, corresponding to chemical procarcinogens according to their damaging characteristics. The origin of these substances and the formation of estrogen genotoxicity lies in the disruption of the inactivation process of catechol estrogens in methylation reactions.

The main epigenetic modification of the human genome is the methylation of cell DNA molecules. DNA methylation does not alter the primary sequence of nucleotides, but is necessary for the functional suppression of certain genes. The phenomenon of hypomethylation-hypermethylation underlies the long-term silencing of various genes, including tumor suppressor genes.

Nutrition and a lifestyle associated with smoking and the consumption of excessive quantities of alcohol determine estrogen metabolism and the availability of methyl groups in the body, as well as epigenetic changes in the DNA of the genome. The assessment of individual risk of breast cancer on the basis of an assay for the expression and methylation of the COMT gene responsible for estrogen metabolism seems relevant.

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The authors declare that there are no conflicts of interest present.