Advances in Molecular OncologyAdvances in Molecular OncologyУспехи молекулярной онкологии2313-805X2413-3787Publishing House ABV Press56810.17650/2313-805X-2023-10-3-24-35REVIEW ARTICLESОБЗОРНЫЕ СТАТЬИSexual dimorphism in cancerМолекулярные механизмы полового диморфизма в канцерогенезеBelitskyG. A.БелицкийГ. А.
Russian Federation

24 Kashirskoe Shosse, Moscow 115522

115522 Москва, Каширское шоссе, 24

KirsanovK. I.КирсановК. И.
Russian Federation

24 Kashirskoe Shosse, Moscow 115522

6 Miklukho-Maklaya St., Moscow 117198

115522 Москва, Каширское шоссе, 24

117198 Москва, ул. Миклухо-Маклая, 6

LesovayaE. A.ЛесоваяЕ. А.
Russian Federation

24 Kashirskoe Shosse, Moscow 115522

9 Vysokovol’tnaya St., Ryazan 390026

115522 Москва, Каширское шоссе, 24

390026 Рязань,ул. Высоковольтная, 9

 

MaksimovaV. P.МаксимоваВ. П.
Russian Federation

24 Kashirskoe Shosse, Moscow 115522

115522 Москва, Каширское шоссе, 24

KrivosheevaL. V.КривошееваЛ. В.
Russian Federation

24 Kashirskoe Shosse, Moscow 115522

115522 Москва, Каширское шоссе, 24

YakubovskayaM. G.ЯкубовскаяМ. Г.
Russian Federation

24 Kashirskoe Shosse, Moscow 115522

6 Miklukho-Maklaya St., Moscow 117198

115522 Москва, Каширское шоссе, 24

117198 Москва, ул. Миклухо-Маклая, 6

mgyakubovskaya@mail.ruN.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of RussiaФГБУ «Национальный медицинский исследовательский центр онкологии им. Н. Н. Блохина» Минздрава РоссииPeoples’ Friendship University of RussiaФГАОУ ВО «Российский университет дружбы народов»I.P. Pavlov Ryazan State Medical UniversityФГБОУ ВО «Рязанский государственный медицинский университет им. акад. И. П. Павлова»1509202310324350910202309102023Copyright ©; 2023, Belitsky G.A., Kirsanov K.I., Lesovaya E.A., Maksimova V.P., Krivosheeva L.V., Yakubovskaya M.G.Copyright ©; 2023, Белицкий Г.А., Кирсанов К.И., Лесовая Е.А., Максимова В.П., Кривошеева Л.В., Якубовская М.Г.2023Belitsky G.A., Kirsanov K.I., Lesovaya E.A., Maksimova V.P., Krivosheeva L.V., Yakubovskaya M.G.Белицкий Г.А., Кирсанов К.И., Лесовая Е.А., Максимова В.П., Кривошеева Л.В., Якубовская М.Г.https://creativecommons.org/licenses/by/4.0https://umo.abvpress.ru/jour/article/view/568

The incidence and mortality of malignant neoplasms of non-reproductive organs both carcinomas and sarcomas in men is one and a half times higher than in women. This is based on genetic differences, which are superimposed by patterns of epigenetic regulation of the expression of sex chromosome genes that determine sex differences in the processes of tissue differentiation, which, in turn, mediates the formation of the hormonal status of the body. Compared to the Y chromosome, the mammalian X chromosome contains several dozen times more genes encoding major regulators of proliferation, metabolism, immunity, and tumor growth inhibitors, as well as X-linked microRNAs affecting transcription factors and cross-regulation by other non-coding RNAs. This results in a female or male gene expression profile that accounts for phenotypic differences. This peculiarity, along with the fact that in female cells on the second inactivatedX chromosome epigenetic repression of the most important genes is reversed and, accordingly, their expression level is doubled, may largely explain the sex disparity in carcinogenesis. The influence of sex hormones and disparity in the expression of antitumor immunity contribute significantly to this difference. A detailed study of the mechanisms underlying sex dimorphism in carcinogenesis will be an essential contribution to fundamental oncology and to the practice of diagnosis, prognosis and personalized treatment of malignances with regard to their gender-specific course. These studies are especially relevant in relation to insufficiently studied soft tissue sarcomas, the ratio of the frequencies of which in men and women varies greatly depending on the histological subtype of the tumor.

Заболеваемость злокачественными новообразованиями нерепродуктивных органов, как карциномами, так и саркомами, и смертность от них у мужчин в 1,5 раза выше, чем у женщин. В основе этого лежат генетические различия, на которые накладываются закономерности эпигенетической регуляции экспрессии генов половых хромосом, определяющие половые различия в процессах дифференцировки тканей и гормонального статуса организма. по сравнению с Y-хромосомой на Х-хромосоме млекопитающих находится в несколько десятков раз больше генов, кодирующих основные регуляторы пролиферации, метаболизма, иммунитета и ингибирования опухолевого роста, а также X-сцепленных микроРНк, влияющих на транскрипционные факторы и перекрестную регуляцию другими некодирующими РНк. В результате образуется профиль экспрессии генов по женскому и мужскому типам, обусловливающий фенотипические различия. этот факт наряду с тем, что в женских клетках в некоторых важнейших генах второй инактивированной X-хромосомы происходит снятие эпигенетической репрессии и, соответственно, удвоение уровня экспрессии, может в значительной степени объяснить «половое неравенство» в канцерогенезе. Существенный вклад в это различие вносят влияние половых гормонов и неравенство в выраженности противоопухолевого иммунитета. Детальное исследование молекулярных механизмов, лежащих в основе полового диморфизма в канцерогенезе, будет существенным вкладом в фундаментальную онкологию, практику диагностики, прогноза и персонализированного лечения злокачественных новообразований с учетом особенностей их течения у мужчин и женщин. Особенно актуальны такие исследования в отношении недостаточно изученных сарком мягких тканей, соотношение частоты возникновения которых у мужчин и женщин сильно варьирует в зависимости от гистологического подтипа опухоли.

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