mesЭкстремальная биомедицинаExtreme Medicine3033-89643033-8972Centre for Strategic Planning of the Federal Medical and Biological Agency10.47183/mes.2025-366mes-366Research ArticleГЛАВНАЯ ТЕМА: ГЕНОМНЫЕ И ПОСТГЕНОМНЫЕ ТЕХНОЛОГИИ КАК ОСНОВА РАЗВИТИЯ ПЕРСОНАЛИЗИРОВАННОЙ МЕДИЦИНЫMAIN TOPIC: GENOMIC AND POST-GENOMIC TECHNOLOGIES AS A BASIS FOR THE DEVELOPMENT OF PERSONALIZED MEDICINEСкрытое бремя хронических неинфекционных заболеваний. Часть 2: распространенность герминальных вариантов, ассоциированных с онкологическими заболеваниями, среди жителей Российской ФедерацииHidden burden of chronic non-communicable diseases. Part 2: prevalence of germline variants associated with cancers among residents of the Russian Federationhttps://orcid.org/0000-0002-9199-6258ЮдинВ. С.YudinV. S.

Юдин Владимир Сергеевич, канд. биол. наук

Москва

Moscow

VYudin@cspfmba.ruhttps://orcid.org/0000-0002-6025-7663МамчурА. А.MamchurA. A.

Мамчур Александра Александровна

Москва

Moscow

AMamchur@cspfmba.ruhttps://orcid.org/0000-0002-7954-2560НиколаеваЕ. А.NikolaevaE. A.

Николаева Екатерина Андреевна

Москва

Moscow

Enikolaeva@cspfmba.ruhttps://orcid.org/0009-0004-7070-5636ИвановМ. В.IvanovM. V.

Иванов Михаил Вячеславович

Москва

Moscow

Mivanov@cspfmba.ruhttps://orcid.org/0000-0001-8977-4384КаштановаД. А.KashtanovaD. A.

Каштанова Дарья Андреевна, канд. мед. наук

Москва

Moscow

DKashtanova@cspfmba.ruhttps://orcid.org/0000-0003-4604-7261ЗеленоваЕ. А.ZelenovaE. A.

Зеленова Елена Андреевна

Москва

Moscow

Ezelenova@cspfmba.ruhttps://orcid.org/0000-0003-0358-0568МитрофановС. И.MitrofanovS. I.

Митрофанов Сергей Игоревич

Москва

Moscow

Mitrofanov@cspfmba.ruhttps://orcid.org/0000-0003-1245-7764СнигирьЕ. А.SnigirE. A.

Снигирь Екатерина Андреевна, канд. биол. наук

Москва

Moscow

Esnigir@cspfmba.ruhttps://orcid.org/0000-0003-3186-8024КузьминаЛ. П.KuzminaL. P.

Кузьмина Людмила Павловна, д-р биол. наук

Москва

Moscow

lpkuzmina@mail.ruhttps://orcid.org/0000-0001-7378-983XКескиновА. А.KeskinovA. A.

Кескинов Антон Артурович, канд. мед. наук

Москва

Moscow

Keskinov@cspfmba.ruЦентр стратегического планирования и управления медико-биологическими рисками здоровью Федерального медико-биологического агентстваРоссияCentre for Strategic Planning and Management of Biomedical Health Risks of the Federal Medical and Biological AgencyRussian FederationНаучно-исследовательский институт медицины труда им. академика Н.Ф. ИзмероваРоссияIzmerov Research Institute of Occupational HealthRussian Federation2026240320262812836Copyright © Юдин В.С., Мамчур А.А., Николаева Е.А., Иванов М.В., Каштанова Д.А., Зеленова Е.А., Митрофанов С.И., Снигирь Е.А., Кузьмина Л.П., Кескинов А.А., 20262026Юдин В.С., Мамчур А.А., Николаева Е.А., Иванов М.В., Каштанова Д.А., Зеленова Е.А., Митрофанов С.И., Снигирь Е.А., Кузьмина Л.П., Кескинов А.А.Yudin V.S., Mamchur A.A., Nikolaeva E.A., Ivanov M.V., Kashtanova D.A., Zelenova E.A., Mitrofanov S.I., Snigir E.A., Kuzmina L.P., Keskinov A.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.extrememedicine.ru/jour/article/view/366Введение

Введение. Онкологические заболевания — ведущая причина смертности в мире. Наследственные (герминальные) мутации в генах предрасположенности к раку вносят существенный вклад в онкогенез (3–12,6% случаев у взрослых). Выявление носителей патогенных / вероятно патогенных (P/LP) вариантов критически важно для профилактики и ранней диагностики рака. Крупномасштабные данные о распространенности таких вариантов в общей популяции Российской Федерации для планирования ресурсов здравоохранения ранее были крайне ограниченны.

Цель

Цель. Оценить распространенность и спектр патогенных и вероятно патогенных герминальных вариантов в генах, ассоциированных с риском развития онкологических заболеваний, в российской популяционной когорте.

Материалы и методы

Материалы и методы. Проведен анализ данных полногеномного секвенирования 116 794 участников (репрезентативная выборка взрослого населения из 86 субъектов РФ). Поиск P/LP-вариантов в онкоассоциированных генах выполнен на основе базы данных ClinVar. Аннотация вариантов проводилась с учетом уровня доказательности. Статистический анализ выполнен с использованием Python (v3.9.12).

Результаты

Результаты. P/LP-варианты обнаружены в 26 онкоассоциированных генах у 2643 (2,26%) участников. Наиболее частый вариант — rs36053993 (MUTYH, 0,28%), частота в РФ ниже мировых баз (ALFA, gnomAD). Варианты уровня А (только варианты с уровнем доказательности «проверено экспертной комиссией») имели суммарно 0,8% людей, уровня B (варианты с уровнями доказательности «проверено экспертной комиссией» и «критерии предоставлены несколькими заявителями, конфликтов нет») — 2,08%, добавление менее надежных уровней (C, D) увеличивало показатель лишь до 2,26%. Наблюдали статистически значимое снижение доли носителей вариантов уровня A с возрастом (p = 0,007), общая доля носителей P/LP-вариантов снижалась незначительно (p = 0,17). Выявлена значительная географическая вариабельность распространенности: от 865 (Республика Башкортостан) до 6250 (Чеченская Республика) вариантов на 100 тыс. населения. В Москве — 2340 на 100 тыс.

Выводы

Выводы. Исследование выявило значимое «скрытое бремя» носительства P/LP онкогерминальных вариантов (2,26%) в российской популяции. Основное бремя обусловлено вариантами с высоким уровнем доказательности (уровень B). Значительная вариабельность распространенности по регионам РФ требует дифференцированного подхода к планированию ресурсов здравоохранения. Полученные данные обосновывают необходимость внедрения программ генетического скрининга (особенно для лиц с семейным анамнезом) и усиленного онконаблюдения для носителей, что является стратегическим направлением для снижения онкозаболеваемости и смертности в группах высокого генетического риска в РФ.

Introduction

Introduction. Cancer is a leading cause of mortality worldwide. Hereditary (germline) mutations in cancer predisposition genes significantly contribute to oncogenesis (accounting for 3–12.6% of adult cases). Identifying carriers of pathogenic/likely pathogenic (P/LP) variants is crucial for cancer prevention and its early detection. Large-scale data on the prevalence of such variants in the general population of the Russian Federation, essential for healthcare resource planning, have been extremely limited until now.

Objective

Objective. To assess the prevalence and spectrum of pathogenic and likely pathogenic germline variants in genes associated with cancer risk in a Russian population cohort.

Materials and methods

Materials and methods. An analysis of whole-genome sequencing data from 116,794 participants (a representative sample of the adult population from 86 federal subjects of the Russian Federation) was conducted. The search for P/LP variants in cancer-associated genes was performed based on the ClinVar database. Variant annotation was carried out considering the level of evidence. Statistical analysis was performed using Python (v3.9.12).

Results

Results. P/LP variants were identified in 26 cancer-associated genes among 2643 participants (2.26%). The most frequent variant was rs36053993 (MUTYH, 0.28%), with its frequency in the Russian Federation being lower than in global databases (ALFA, gnomAD). Level A variants (only those with the “reviewed by expert panel” level of evidence) were carried by 0.8% of individuals collectively. Level B variants (those with the “reviewed by expert panel” and “criteria provided, multiple submitters, no conflicts” levels of evidence) were carried by 2.08%. The inclusion of less reliable evidence levels (C, D) increased this proportion only marginally, to 2.26%. A statistically significant decrease in the proportion of carriers of Level A variants with age was observed (p = 0.007), while the overall proportion of P/LP variant carriers decreased only slightly (p = 0.17). Substantial geographical variability in prevalence was identified, ranging from 865 (Bashkortostan) to 6250 (Chechnia) variants per 100,000 population. In Moscow, the prevalence was 2340 per 100,000.

Conclusions

Conclusions. The study revealed a significant “hidden burden” of P/LP oncogenic germline variant carriers (2.26%) in the Russian population. The primary burden is attributed to variants with a high level of evidence (Level B). The substantial variability in prevalence across regions of the Russian Federation necessitates a differentiated approach to healthcare resource planning. The data obtained substantiate the need for implementing genetic screening programs (especially for individuals with a family history) and enhanced oncological surveillance for carriers. This represents a strategic direction for reducing cancer incidence and mortality in high genetic risk groups within the Russian Federation.

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