• Login
    View Item 
    •   Home
    • The Christie Research Publications Repository
    • All Christie Publications
    • View Item
    •   Home
    • The Christie Research Publications Repository
    • All Christie Publications
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of ChristieCommunitiesTitleAuthorsIssue DateSubmit DateSubjectsThis CollectionTitleAuthorsIssue DateSubmit DateSubjects

    My Account

    LoginRegister

    Local Links

    The Christie WebsiteChristie Library and Knowledge Service

    Statistics

    Display statistics

    Breast cancer risk stratification in women of screening age: Incremental effects of adding mammographic density, polygenic risk, and a gene panel

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    Evans.pdf
    Size:
    460.2Kb
    Format:
    PDF
    Description:
    Identified with Open Access button
    Download
    Authors
    Evans, D Gareth R
    van Veen, E. M.
    Harkness, E. F.
    Brentnall, A. R.
    Astley, Susan M
    Byers, Helen
    Woodward, Emma R
    Sampson, S.
    Southworth, J.
    Howell, Sacha J
    Maxwell, Anthony J
    Newman, W. G.
    Cuzick, J.
    Howell, Anthony
    Show allShow less
    Affiliation
    Division of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom
    Issue Date
    2022
    
    Metadata
    Show full item record
    Abstract
    Purpose: There is great promise in breast cancer risk stratification to target screening and prevention. It is unclear whether adding gene panels to other risk tools improves breast cancer risk stratification and adds discriminatory benefit on a population basis. Methods: In total, 10,025 of 57,902 women aged 46 to 73 years in the Predicting Risk of Cancer at Screening study provided DNA samples. A case-control study was used to evaluate breast cancer risk assessment using polygenic risk scores (PRSs), cancer gene panel (n = 33), mammographic density (density residual [DR]), and risk factors collected using a self-completed 2-page questionnaire (Tyrer-Cuzick [TC] model version 8). In total, 525 cases and 1410 controls underwent gene panel testing and PRS calculation (18, 143, and/or 313 single-nucleotide polymorphisms [SNPs]). Results: Actionable pathogenic variants (PGVs) in BRCA1/2 were found in 1.7% of cases and 0.55% of controls, and overall PGVs were found in 6.1% of cases and 1.3% of controls. A combined assessment of TC8-DR-SNP313 and gene panel provided the best risk stratification with 26.1% of controls and 9.7% of cases identified at <1.4% 10-year risk and 9.01% of controls and 23.3% of cases at ≥8% 10-year risk. Because actionable PGVs were uncommon, discrimination was identical with/without gene panel (with/without: area under the curve = 0.67, 95% CI = 0.64-0.70). Only 7 of 17 PGVs in cases resulted in actionable risk category change. Extended case (n = 644)-control (n = 1779) series with TC8-DR-SNP143 identified 18.9% of controls and only 6.4% of stage 2+ cases at <1.4% 10-year risk and 20.7% of controls and 47.9% of stage 2+ cases at ≥5% 10-year risk. Conclusion: Further studies and economic analysis will determine whether adding panels to PRS is a cost-effective strategy for risk stratification.
    Citation
    Evans DGR, van Veen EM, Harkness EF, Brentnall AR, Astley SM, Byers H, et al. Breast cancer risk stratification in women of screening age: Incremental effects of adding mammographic density, polygenic risk, and a gene panel. Genetics in Medicine. Elsevier BV; 2022.
    Journal
    Genetics in Medicine
    URI
    http://hdl.handle.net/10541/625214
    DOI
    10.1016/j.gim.2022.03.009
    PubMed ID
    35426792
    Additional Links
    https://dx.doi.org/10.1016/j.gim.2022.03.009
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.gim.2022.03.009
    Scopus Count
    Collections
    All Christie Publications

    entitlement

    Related articles

    • A case-control evaluation of 143 single nucleotide polymorphisms for breast cancer risk stratification with classical factors and mammographic density.
    • Authors: Brentnall AR, van Veen EM, Harkness EF, Rafiq S, Byers H, Astley SM, Sampson S, Howell A, Newman WG, Cuzick J, Evans DGR
    • Issue date: 2020 Apr 15
    • The impact of a panel of 18 SNPs on breast cancer risk in women attending a UK familial screening clinic: a case-control study.
    • Authors: Evans DG, Brentnall A, Byers H, Harkness E, Stavrinos P, Howell A, FH-risk study Group, Newman WG, Cuzick J
    • Issue date: 2017 Feb
    • Breast cancer pathology and stage are better predicted by risk stratification models that include mammographic density and common genetic variants.
    • Authors: Evans DGR, Harkness EF, Brentnall AR, van Veen EM, Astley SM, Byers H, Sampson S, Southworth J, Stavrinos P, Howell SJ, Maxwell AJ, Howell A, Newman WG, Cuzick J
    • Issue date: 2019 Jul
    • Joint association of mammographic density adjusted for age and body mass index and polygenic risk score with breast cancer risk.
    • Authors: Vachon CM, Scott CG, Tamimi RM, Thompson DJ, Fasching PA, Stone J, Southey MC, Winham S, Lindström S, Lilyquist J, Giles GG, Milne RL, MacInnis RJ, Baglietto L, Li J, Czene K, Bolla MK, Wang Q, Dennis J, Haeberle L, Eriksson M, Kraft P, Luben R, Wareham N, Olson JE, Norman A, Polley EC, Maskarinec G, Le Marchand L, Haiman CA, Hopper JL, Couch FJ, Easton DF, Hall P, Chatterjee N, Garcia-Closas M
    • Issue date: 2019 May 22
    • Use of Single-Nucleotide Polymorphisms and Mammographic Density Plus Classic Risk Factors for Breast Cancer Risk Prediction.
    • Authors: van Veen EM, Brentnall AR, Byers H, Harkness EF, Astley SM, Sampson S, Howell A, Newman WG, Cuzick J, Evans DGR
    • Issue date: 2018 Apr 1
    DSpace software (copyright © 2002 - 2023)  DuraSpace
    Quick Guide | Contact Us
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.