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25.10.2022 | Preclinical study

Methylation of promoter region of BRCA1 gene versus pathogenic variants of gene: risk factor or clinical marker of breast cancer

verfasst von: Olga Lobanova, Nataliia Medvedieva, Liliia Fishchuk, Olha Dubitska, Valeriy Cheshuk, Roman Vereshchako, Liubov Zakhartseva, Zoia Rossokha, Natalia Gorovenko

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 3/2022

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Abstract

Background

In this study, we compared the contribution of pathogenic variants of the BRCA1/2 genes (5382insC, 185delAG, 6174delT, 4153delA, T300G) and hypermethylation of the BRCA1 gene promoter region to the risk of breast cancer and clinical features in women.

Methods

This study enrolled 74 women (tumor tissue, blood) with newly diagnosed breast cancer and 62 women (blood) without oncological pathology (control group). Molecular genetic testing of samples and determination of hypermethylation status were performed on freshly collected material with the addition of a preservative before the procedure of DNA isolation.

Results

Hypermethylation of the BRCA1 gene promoter in women is a risk breast cancer factor (χ² = 19.10, p = 0.001, OR = 16.25 (3.67–71.92)) and is more common than major pathogenic variants in the BRCA1/2 genes. The patients with the BRCA1 gene promoter hypermethylation were more likely to be diagnosed with late-stage metastatic cancer (χ² = 4.31, p = 0.038, OR = 4.04 (1.19–13.65)). Hypermethylation of the BRCA1 gene promoter was predominant in tumor tissue among BC patients without family history compared to patients with cancer in relatives.

Conclusion

We proved that hypermethylation of the BRCA1 gene promoter is a risk factor for breast cancer and possibly an early biological marker of clinical onset, as its presence contributed to rapid disease progression with metastasis. The high frequency of hypermethylation in the examined breast cancer patients may be a consequence of environmental factors pressure on the risk of the disease development. Further large-scale studies are needed for the clinical application of the results.

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Titel: Methylation of promoter region of BRCA1 gene versus pathogenic variants of gene: risk factor or clinical marker of breast cancer
verfasst von: Olga Lobanova
Nataliia Medvedieva
Liliia Fishchuk
Olha Dubitska
Valeriy Cheshuk
Roman Vereshchako
Liubov Zakhartseva
Zoia Rossokha
Natalia Gorovenko
Publikationsdatum: 25.10.2022
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 3/2022
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-022-06774-2

Springer Medizin

Methylation of promoter region of BRCA1 gene versus pathogenic variants of gene: risk factor or clinical marker of breast cancer