medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/ms2025-525medsovet-9701Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHГенетические особенности пациенток с диагнозом «рак молочной железы» и женщин с онкологически отягощенным семейным анамнезомGenetic features of breast cancer patients and women with a cancer-prone family historyhttps://orcid.org/0000-0003-2797-1926КудрявцеваЕ. В.KudryavtsevaE. V.

Кудрявцева Елена Владимировна - д.м.н., доцент, ведущий научный сотрудник отдела сохранения репродуктивной функции.

620028, Екатеринбург, ул. Репина, д. 3

Elena V. Kudryavtseva - Dr. Sci. (Med.), Associate Professor, Leading Researcher, Department of Reproductive Function Preservation, Ural Research Institute of Maternal and Child Health.

1, Repin St., Ekaterinburg, 620028

elenavladpopova@yandex.ruhttps://orcid.org/0009-0003-8070-6336КнышО. Е.KnyshO. E.

Кныш Олег Евгеньевич - студент Института клинической медицины.

620028, Екатеринбург, ул. Репина, д. 3

Oleg E. Knysh - Student at the Institute of Clinical Medicine, Urals State Medical University.

3, Repin St., Ekaterinburg, 620028

knysh_oleg4@bk.ruhttps://orcid.org/0000-0002-0342-4007ПеткауВ. В.PetkauV. V.

Петкау Владислав Владимирович - к.м.н., заместитель главного врача по лекарственной терапии, СООД; доцент кафедры онкологии и лучевой диагностики, УГМУ.

620036, Екатеринбург, ул. Соболева, д. 29; 620028, Екатеринбург, ул. Репина, д. 3

Vladislav V. Petkau - Cand. Sci. (Med.), Deputy Chief Physician for Drug Therapy, Sverdlovsk Regional Oncological Dispensary; Associate Professor of the Department of Oncology and Radiation Diagnostics, Urals State Medical University.

29, Sobolev St., Ekaterinburg, 620036; 3, Repin St., Ekaterinburg, 620028

vpetaku@yandex.ruhttps://orcid.org/0009-0009-7426-0052БикбулатоваЭ. Р.BikbulatovaE. R.

Бикбулатова Элина Ринатовна - студент Института клинической медицины.

620028, Екатеринбург, ул. Репина, д. 3

Elina R. Bikbulatova - Student at the Institute of Clinical Medicine, Urals State Medical University.

3, Repin St., Ekaterinburg, 620028

kick258@mail.ruhttps://orcid.org/0009-0001-1289-4297УсынинИ. Г.UsyninI. G.

Усынин Иван Георгиевич - врач-онколог, ГКБ №40; ассистент кафедры онкологии и лучевой диагностики, УГМУ.

620102, Екатеринбург, ул. Волгоградская, д. 189; 620028, Екатеринбург, ул. Репина, д. 3

Ivan G. Usynin - Oncologist, City Clinical Hospital No. 40; Assistant at the Department of Oncology and Radiation Diagnostics, Urals State Medical University.

189, Volgogradskaya St., Ekaterinburg, 620102; 3, Repin St., Ekaterinburg, 620028

Уральский научно-исследовательский институт охраны материнства и младенчестваРоссияUral Research Institute of Maternal and Child HealthRussian FederationУральский государственный медицинский университетРоссияUrals State Medical UniversityRussian FederationУральский государственный медицинский университет; Свердловский областной онкологический диспансерРоссияUrals State Medical University; Sverdlovsk Regional Oncological DispensaryRussian FederationУральский государственный медицинский университет; Городская клиническая больница №40РоссияUrals State Medical University; City Clinical Hospital No. 40Russian Federation202501012026021130140Copyright © Кудрявцева Е.В., Кныш О.Е., Петкау В.В., Бикбулатова Э.Р., Усынин И.Г., 20262026Кудрявцева Е.В., Кныш О.Е., Петкау В.В., Бикбулатова Э.Р., Усынин И.Г.Kudryavtseva E.V., Knysh O.E., Petkau V.V., Bikbulatova E.R., Usynin I.G.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/9701Введение

Введение. 5–10% случаев рака молочной железы (РМЖ) ассоциированы с герминальными мутациями (патогенными генетическими вариантами – PV) в генах предрасположенности. В России рекомендовано определение «8 частых» вариантов генов BRCA1,2 методом ПЦР, а при отрицательном результате – тестирование с помощью высокопроизводительного секвенирования (NGS – next generation sequensing). Большинство предшествующих исследований PV при РМЖ затрагивали гены BRCA1,2, не раскрывая потенциал прочих генов кандидатов.

Цель

Цель. Проанализировать частоту встречаемости и спектр PV в генах-кандидатах у пациенток с диагнозом РМЖ и здоровых женщин с онкологически отягощенным семейным анамнезом.

Материалы и методы

Материалы и методы. Ретроспективно проанализированы результаты NGS-тестирования клеток периферической крови 291 женщины по панели из 26 генов, ассоциированных с РМЖ. Участницы разделены на 2 группы: 1-я – пациентки с РМЖ в анамнезе; 2-я – здоровые женщины с наличием родственниц 1–2-й линии с установленным диагнозом РМЖ или рак яичников.

Результаты

Результаты. PV в 1-й группе встречались существенно чаще, чем во 2-й (соответственно 21,92 и 8,3%, р = 0,0012). Манифестация РМЖ при наличии PV происходила раньше, чем у женщин, у которых значимые генетические варианты выявлены не были (39,3 ± 1 против 44 ± 0,9 лет, р = 0,01). PV в генах BRCA1,2 были выявлены соответственно у 14,3% в 1-й группе и у 6,2% во 2-й группе. Наиболее часто выявлялись варианты BRCA1 c.5266dupC и BRCA1 c.5251C>T. PV в BRCA1,2 составили лишь 68,18% от всех PV, подтверждая необходимость анализа и других генов. Также в 1-й группе высокую встречаемость демонстрировали PV CHEK2 (4,8%) – значительно чаще, чем во 2-й (р = 0,0076). CHEK2 c.1100delC составил 57% среди PV гена CHEK2. В 20% случаев выявлялись варианты неопределенного клинического значения – VUS (англ. variants of uncertain significance).

Заключение

Заключение. NGS позволяет обнаружить широкий спектр значимых генетических вариантов, однако, требует высокой квалификации для корректной интерпретации результатов.

Introduction

Introduction. 5–10% of breast cancer (BC) cases are associated with germline pathogenic variants (PVs) in predisposition genes. In Russia, detection of “8 frequent” BRCA1,2 variants by PCR is recommended, with next generation sequensing (NGS) performed only at a second stage. Most studies on BC PVs have focused on BRCA1,2, not exploring other candidate genes.

Aim

Aim. Analyze the frequency and spectrum of PVs in candidate genes in patients with BC and healthy women with a family history of cancer.

Materials and methods

Materials and methods. Results of NGS testing (26-gene panel) on peripheral blood from 291 women were retrospectively analyzed. Participants were divided into 2 groups: 1 – patients with a history of BC (n = 146); 2 – women with 1st/2nd degree relatives diagnosed with BC or ovarian cancer (n = 145).

Results

Results. PVs were 2.5 times more frequent in Group 1 (21.2%) vs Group 2 (8.3%), р = 0,0012. BC onset with PVs occurred earlier than in women in whom significant genetic variants were not identified (39.3 ± 1 vs 44 ± 0,9 years, р = 0,01). PV in the BRCA1,2 genes were detected in 14.3% of group 1 and 6.2% of group 2, respectively. The most frequently detected variants were. BRCA1,2 PVs were most frequent (14.3% Grp1, 6.2% Grp2); Most common PVs were in BRCA1: c.5266dupC, c.4035delA. BRCA1,2 PVs comprised only 68,18% of all PVs, confirming importance of testing other genes. CHEK2 PVs were frequent in Group 1 (4.8%), 7 times higher than Group 2 (р = 0,0076). CHEK2:c.1100delC comprised 57% of these. 20.4% were VUS (variants of uncertain significance), often in non-BRCA genes. PVs in Group 2 were 8 times higher than general population rates.

Conclusion

Conclusion. NGS enables detection of a full spectrum of clinically significant variants, requiring high expertise for interpretation.

наследственный рак молочной железыгенетическое тестированиегенетикасеквенированиеNGSмутациипатогенные генетические вариантыBRCA1BRCA2CHEK2hereditary breast cancergenetic testinggeneticssequencingNGSmutationspathogenic genetic variantsBRCA1BRCA2CHEK2ReferencesSedeta ET, Jobre B, Avezbakiyev B. Breast cancer: Global patterns of incidence, mortality, and trends. Am Soc Clin Oncol. 2023;41(16 Suppl.):10528. https://doi.org/10.1200/JCO.2023.41.16_suppl.10528.Sedeta ET, Jobre B, Avezbakiyev B. Breast cancer: Global patterns of incidence, mortality, and trends. Am Soc Clin Oncol. 2023;41(16 Suppl.):10528. https://doi.org/10.1200/JCO.2023.41.16_suppl.10528.Каприн АД, Старинский ВВ, Шахзадова АО (ред.). Злокачественные ново­ образования в России в 2023 году (заболеваемость и смертность). М.: МНИОИ им. П.А. Герцена – филиал ФГБУ «НМИЦ радиологии» Минздрава России; 2024. 256 с. 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The authors declare that there are no conflicts of interest present.