Opin vísindi

Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers

Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers


Title: Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers
Author: GEMO Study Collaborators
EMBRACE Collaborators
SWE-BRCA Investigators
kConFab Investigators
HEBON Investigators
Date: 2022-10-06
Language: English
Scope: 1
University/Institute: Landspitali - The National University Hospital of Iceland
Department: Clinical Laboratory Services, Diagnostics and Blood Bank
Series: Communications Biology; 5(1)
ISSN: 2399-3642
DOI: 10.1038/s42003-022-03978-6
Subject: Náttúrufræðingar; BRCA1 Protein/genetics; BRCA2 Protein/genetics; Breast Neoplasms/genetics; DNA Copy Number Variations; Female; Genetic Predisposition to Disease; Heterozygote; Humans; RNA, Messenger; Agricultural and Biological Sciences (all); Biochemistry, Genetics and Molecular Biology (all); Medicine (miscellaneous)
URI: https://hdl.handle.net/20.500.11815/3525

Show full item record

Citation:

GEMO Study Collaborators , EMBRACE Collaborators , SWE-BRCA Investigators , kConFab Investigators & HEBON Investigators 2022 , ' Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers ' , Communications Biology , vol. 5 , no. 1 , pp. 1061 . https://doi.org/10.1038/s42003-022-03978-6

Abstract:

The contribution of germline copy number variants (CNVs) to risk of developing cancer in individuals with pathogenic BRCA1 or BRCA2 variants remains relatively unknown. We conducted the largest genome-wide analysis of CNVs in 15,342 BRCA1 and 10,740 BRCA2 pathogenic variant carriers. We used these results to prioritise a candidate breast cancer risk-modifier gene for laboratory analysis and biological validation. Notably, the HR for deletions in BRCA1 suggested an elevated breast cancer risk estimate (hazard ratio (HR) = 1.21), 95% confidence interval (95% CI = 1.09-1.35) compared with non-CNV pathogenic variants. In contrast, deletions overlapping SULT1A1 suggested a decreased breast cancer risk (HR = 0.73, 95% CI 0.59-0.91) in BRCA1 pathogenic variant carriers. Functional analyses of SULT1A1 showed that reduced mRNA expression in pathogenic BRCA1 variant cells was associated with reduced cellular proliferation and reduced DNA damage after treatment with DNA damaging agents. These data provide evidence that deleterious variants in BRCA1 plus SULT1A1 deletions contribute to variable breast cancer risk in BRCA1 carriers.

Description:

Publisher Copyright: © 2022. The Author(s). © 2022. The Author(s).

Files in this item

This item appears in the following Collection(s)