The role of polymorphic markers of matrix metalloproteinase genes in the tumoral progression of breast cancer

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.

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