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Review
. 2021 Dec 21;66(12):760-767.
doi: 10.51620/0869-2084-2021-66-12-760-767.

Clinical significance of gene polymorphisms for hereditary predisposition to breast and ovarian cancer (review of literature)

D I Vodolazhsky  1 , A V Mayakovskaya  1 , A V Kubyshkin  1 , K A Aliev  1 , I I Fomochkina  1
Affiliations
Review

Clinical significance of gene polymorphisms for hereditary predisposition to breast and ovarian cancer (review of literature)

D I Vodolazhsky et al. Klin Lab Diagn. .

Abstract

The review presents classical and modern views on the molecular genetic causes underlying hereditary predisposition to breast and ovarian cancer. A computerized literature search was carried out in the electronic databases MEDLINE, Scopus, and Web of Science, published between January 1994 and May 2021, using the keywords: «hereditary breast and ovarian cancer», «BRCA» and «DNA repair». Current views on the role of germline mutations in genes for susceptibility to breast cancer (BC): BRCA1, BRCA2, PALB2, TP53, CHEK2, PTEN, ATM, and PPM1D are presented. The role of a complex of genes involved in homologous DNA repair and causing other hereditary oncological diseases is considered. The role of the loss of heterozygosity in these genes, which increases the level of chromosomal instability and leads to an increased risk of malignant transformation, is considered. Germinal mutations in the genes under consideration in 90% of clinical cases are the cause of initiation of tissue malignancy and greatly increase the risk of developing hereditary breast cancer and OC. The review emphasizes the complex nature of pathogenesis and significant polymorphism of genetic targets for hereditary breast cancer and OC. It is concluded that it is necessary to use NGS panels for complex screening of genes of hereditary susceptibility to these oncological diseases. The review provides data on the clinical significance of each group of genes of hereditary predisposition in the pathogenesis of breast cancer and OC, and also demonstrates the possible role of methylation of the promoter regions of genes and the state of mitochondrial DNA in the development of these pathologies. The purpose of this review was to broaden the horizons of specialists in the field of oncology and clinical diagnostics in the context of the rapidly expanding spectrum of molecular genetic markers of hereditary breast and ovarian cancers.

Keywords: BRCA ½; MRN; NBS1; SNP; hereditary breast cancer; hereditary ovarian cancer; mitochondrial DNA; penetrance; review.

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Conflict of interest statement

The authors declare no conflict of interest.

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