Russian Journal of BiotherapyRussian Journal of BiotherapyРоссийский биотерапевтический журнал1726-97841726-9792Publishing House ABV Press144710.17650/1726-9784-2024-23-2-10-24REVIEWОБЗОР ЛИТЕРАТУРЫThe role of polymorphic markers of matrix metalloproteinase genes in the tumoral progression of breast cancerРоль полиморфных маркеров генов матриксных металлопротеиназ в опухолевой прогрессии рака молочной железыhttps://orcid.org/0000-0002-7754-5231PavlovaN. V.ПавловаН. В.
Russian Federation

Nadezhda V. Pavlova 

1 Kuybysheva St., Belgorod 308010;85 Pobedy St., Belgorod 308015

308010 Белгород, ул. Куйбышева, 1;308015 Белгород, ул. Победы, 85

https://orcid.org/0000-0002-9956-4775DyominS. S.ДёминС. С.
Russian Federation

Sergey S. Dyomin 

1 Kuybysheva St., Belgorod 308010;85 Pobedy St., Belgorod 308015

Сергей Сергеевич Дёмин 

308010 Белгород, ул. Куйбышева, 1;308015 Белгород, ул. Победы, 85

doctor.dyomin@gmail.comhttps://orcid.org/0000-0003-1254-6134ChurnosovM. I.ЧурносовМ. И.
Russian Federation

Mikhail I. Churnosov 

85 Pobedy St., Belgorod 308015

308015 Белгород, ул. Победы, 85

https://orcid.org/0000-0002-5652-0166PonomarenkoI. V.ПономаренкоИ. В.
Russian Federation

Irina V. Ponomarenko 

85 Pobedy St., Belgorod 308015

308015 Белгород, ул. Победы, 85

Belgorod Regional Oncology DispensaryОГБУЗ «Белгородский областной онкологический диспансер»Belgorod State National Research University, Russian Ministry of Education and ScienceФГАОУ ВО «Белгородский государственный национальный исследовательский университет» Минобрнауки России2606202423210242606202426062024https://bioterapevt.abvpress.ru/jour/article/view/1447

Aim. Summarizing current insights into the pathogenesis of breast cancer (BC) from the perspective of candidate gene involvement, specifically matrix metalloproteinase genes (MMPs), and their clinicopathological significance.

Materials and methods. Source retrieval for the study was conducted using PubMed, Medline, Cochrane Library, eLibrary, NHGRI-EBI Catalog of GwAS databases. Publications from January 2004 to December 2022 were included. A total of 158 sources related to the role of MMPs in BC development were identified. Search queries encompassed associations of different MMPs loci with BC formation and progression. This review included 60 selected works, adhering to inclusion criteria based on comprehensive genome-wide association studies (GwAS) and representative patient cohort association studies with adequate statistical power. Data encompassing clinicopathological significance (association with BC molecular subtype, survival, disease prognosis, metastasis risk, and malignancy grade) of MMPs polymorphic markers were incorporated. Excluded were data from MMPs gene association studies with non-carcinoma breast diseases and studies conducted on small, non-representative patient and control samples.

Results. The clinical presentation of BC, treatment nuances, and patient survival depend on the interaction of various risk factors, including genetic ones. The association between MMPs gene polymorphisms and BC is actively investigated. Well-studied polymorphisms include MMP1 (rs1799750), MMP2 (rs243865), and MMP9 (rs3918242, rs17576, rs2250889, rs3787268), which have shown correlations with BC development, metastasis, and survival. Literature data significantly support the association with BC – risk susceptibility, malignancy grade, regional and distant metastasis, and patient survival – for polymorphic variants 2G rs1799750 MMP1, T rs3918242 MMP9, G rs17576 MMP9,  G rs2250889 MMP9 (risk factors), and T rs243865 MMP2 (protective factor). In contrast, data on most other MMP polymorphisms (rs3787268 MMP9, rs1940475 MMP8, etc.) are limited and often discordant.

Conclusion. Continuing research into the association between MMPs gene polymorphisms and BC is an important scientific and practical task, aiming to expand empirical knowledge in this domain and ultimately establish definitive insights into their influence on disease progression and prognosis.

Цель исследования – обобщение актуальных представлений о патогенетике рака молочной железы (РМЖ) с позиций вовлеченности генов – кандидатов матриксных металлопротеиназ (MMPs) и их клинико-патологического значения.

Материалы и методы. Поиск источников по теме работы осуществляли в системах PubMed, Medline, Cochrane Library, eLibrary, NHGRI-EBI Catalog of GwAS. За период с января 2004 г. по декабрь 2022 г. найдено 158 публикаций, посвященных изучению роли MMPs в развитии РМЖ. Поисковые запросы включали данные об ассоциациях различных локусов MMPs с формированием и течением РМЖ. В настоящий обзор включены 60 работ из общей выборки. Критериями включения источников являлись данные полногеномных ассоциативных исследований (GwAS), ассоциативных исследований, выполненных на репрезентативных выборках больных, с необходимой мощностью исследования. Включали данные, характеризующие клинико-патологическое значение (связь с молекулярным подтипом РМЖ, выживаемостью и прогнозом заболевания, риском метастазирования и степенью злокачественности) полиморфных маркеров MMPs. Исключены данные ассоциативных исследований генов MMPs с развитием злокачественных новообразований молочной железы, морфологически не являющихся карциномами, выполненные на малочисленных (не репрезентативных) выборках групп больных и контроля.

Результаты. Клиническая картина РМЖ, особенности лечения, а также выживаемость больных зависят от взаимодействия разнообразных факторов риска, в том числе и генетических. Связь полиморфизмов генов ММРs с РМЖ активно изучается. Наиболее хорошо изученными являются полиморфизмы генов MMP1 (rs1799750), MMP2 (rs243865), MMP9 (rs3918242, rs17576, rs2250889, rs3787268), для которых продемонстрирована связь с развитием РМЖ, метастазированием и выживаемостью. В значительной степени однозначные данные литературы о связи с РМЖ (риском развития заболевания, степенью злокачественности карцином, регионарным и отдаленным метастазированием, снижением выживаемости больных) представлены для полиморфных вариантов 2G rs1799750 MMP1, Т rs3918242 MMP9, G rs17576 MMP9, G rs2250889 MMP9 (факторы риска) и Т rs243865 MMP2 (протективный фактор). Наряду с этим по большинству других полиморфизмов MMPs (rs3787268 MMP9, rs1940475 MMP8 и др.) данные малочисленны, а также нередко не согласуются между собой.

Заключение. Продолжение исследований по изучению связи полиморфизма генов MMPs с РМЖ с целью расширения экспериментальных данных по этому вопросу является важной научно-практической задачей и позволит выработать «однозначные» представления об их влиянии на течение и прогноз заболевания.

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