Insights into genetic modifiers of breast cancer risk in carriers of BRCA1 and BRCA2 pathogenic variants

Abstract Pathogenic variants in BRCA1 and BRCA2 are associated with an increased risk of developing several types of cancer, including breast cancer. However, the risk varies by other environmental and genetic factors present in carriers of mutation. To understand the value of these factors more cle...

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Main Authors: Roksana Dwornik, Katarzyna Białkowska
Format: Article
Language:English
Published: BMC 2025-04-01
Series:Hereditary Cancer in Clinical Practice
Online Access:https://doi.org/10.1186/s13053-025-00313-y
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author Roksana Dwornik
Katarzyna Białkowska
author_facet Roksana Dwornik
Katarzyna Białkowska
author_sort Roksana Dwornik
collection DOAJ
description Abstract Pathogenic variants in BRCA1 and BRCA2 are associated with an increased risk of developing several types of cancer, including breast cancer. However, the risk varies by other environmental and genetic factors present in carriers of mutation. To understand the value of these factors more clearly, a number of common genetic susceptibility variants have been studied through genome-wide association studies as potential genetic risk modifiers for BRCA1 and BRCA2 pathogenic variants carriers. Several studies have identified specific polymorphisms that may influence the risk of breast cancer development, either by increasing or reducing susceptibility. These variants are implicated in biological pathways such as DNA damage repair, hormonal regulation or cell proliferation. The identification and understanding of key genetic modifiers may provide valuable insights into development of personalized prevention, targeted therapies and screening strategies for high-risk individuals. This review presents the overview of known genetic risk modifiers for carriers of BRCA1 and BRCA2 pathogenic variants, their potential impact on risk, and their functional roles. Furthermore, it highlights the need for further research directions, including understanding the biological role of genetic modifiers in cancer development and the refinement of risk assessment models.
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spelling doaj-art-e035ee206dce40ab993b82f1a83f822d2025-08-20T02:10:53ZengBMCHereditary Cancer in Clinical Practice1897-42872025-04-0123111110.1186/s13053-025-00313-yInsights into genetic modifiers of breast cancer risk in carriers of BRCA1 and BRCA2 pathogenic variantsRoksana Dwornik0Katarzyna Białkowska1Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical UniversityDepartment of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical UniversityAbstract Pathogenic variants in BRCA1 and BRCA2 are associated with an increased risk of developing several types of cancer, including breast cancer. However, the risk varies by other environmental and genetic factors present in carriers of mutation. To understand the value of these factors more clearly, a number of common genetic susceptibility variants have been studied through genome-wide association studies as potential genetic risk modifiers for BRCA1 and BRCA2 pathogenic variants carriers. Several studies have identified specific polymorphisms that may influence the risk of breast cancer development, either by increasing or reducing susceptibility. These variants are implicated in biological pathways such as DNA damage repair, hormonal regulation or cell proliferation. The identification and understanding of key genetic modifiers may provide valuable insights into development of personalized prevention, targeted therapies and screening strategies for high-risk individuals. This review presents the overview of known genetic risk modifiers for carriers of BRCA1 and BRCA2 pathogenic variants, their potential impact on risk, and their functional roles. Furthermore, it highlights the need for further research directions, including understanding the biological role of genetic modifiers in cancer development and the refinement of risk assessment models.https://doi.org/10.1186/s13053-025-00313-y
spellingShingle Roksana Dwornik
Katarzyna Białkowska
Insights into genetic modifiers of breast cancer risk in carriers of BRCA1 and BRCA2 pathogenic variants
Hereditary Cancer in Clinical Practice
title Insights into genetic modifiers of breast cancer risk in carriers of BRCA1 and BRCA2 pathogenic variants
title_full Insights into genetic modifiers of breast cancer risk in carriers of BRCA1 and BRCA2 pathogenic variants
title_fullStr Insights into genetic modifiers of breast cancer risk in carriers of BRCA1 and BRCA2 pathogenic variants
title_full_unstemmed Insights into genetic modifiers of breast cancer risk in carriers of BRCA1 and BRCA2 pathogenic variants
title_short Insights into genetic modifiers of breast cancer risk in carriers of BRCA1 and BRCA2 pathogenic variants
title_sort insights into genetic modifiers of breast cancer risk in carriers of brca1 and brca2 pathogenic variants
url https://doi.org/10.1186/s13053-025-00313-y
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AT katarzynabiałkowska insightsintogeneticmodifiersofbreastcancerriskincarriersofbrca1andbrca2pathogenicvariants