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  1. Article ; Online: A comparative analysis of risk factor associations with interval and screen-detected breast cancers: A large UK prospective study.

    Barnes, Isobel / Garcia-Closas, Montserrat / Gathani, Toral / Sweetland, Siân / Floud, Sarah / Reeves, Gillian K

    International journal of cancer

    2024  

    Abstract: The associations of certain factors, such as age and menopausal hormone therapy, with breast cancer risk are known to differ for interval and screen-detected cancers. However, the extent to which associations of other established breast cancer risk ... ...

    Abstract The associations of certain factors, such as age and menopausal hormone therapy, with breast cancer risk are known to differ for interval and screen-detected cancers. However, the extent to which associations of other established breast cancer risk factors differ by mode of detection is unclear. We investigated associations of a wide range of risk factors using data from a large UK cohort with linkage to the National Health Service Breast Screening Programme, cancer registration, and other health records. We used Cox regression to estimate adjusted relative risks (RRs) and 95% confidence intervals (CIs) for associations between risk factors and breast cancer risk. A total of 9421 screen-detected and 5166 interval cancers were diagnosed in 517,555 women who were followed for an average of 9.72 years. We observed the following differences in risk factor associations by mode of detection: greater body mass index (BMI) was associated with a smaller increased risk of interval (RR per 5 unit increase 1.07, 95% CI 1.03-1.11) than screen-detected cancer (RR 1.27, 1.23-1.30); having a first-degree family history was associated with a greater increased risk of interval (RR 1.81, 1.68-1.95) than screen-detected cancer (RR 1.52, 1.43-1.61); and having had previous breast surgery was associated with a greater increased risk of interval (RR 1.85, 1.72-1.99) than screen-detected cancer (RR 1.34, 1.26-1.42). As these differences in associations were relatively unchanged after adjustment for tumour grade, and are in line with the effects of these factors on mammographic density, they are likely to reflect the effects of these risk factors on screening sensitivity.
    Language English
    Publishing date 2024-04-26
    Publishing country United States
    Document type Journal Article
    ZDB-ID 218257-9
    ISSN 1097-0215 ; 0020-7136
    ISSN (online) 1097-0215
    ISSN 0020-7136
    DOI 10.1002/ijc.34968
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Assessment of breast cancer risk: which tools to use?

    Garcia-Closas, Montserrat / Chatterjee, Nilanjan

    The Lancet. Oncology

    2019  Volume 20, Issue 4, Page(s) 463–464

    MeSH term(s) Breast ; Breast Neoplasms ; Humans ; Risk Assessment
    Language English
    Publishing date 2019-02-21
    Publishing country England
    Document type Journal Article ; Comment
    ZDB-ID 2049730-1
    ISSN 1474-5488 ; 1470-2045
    ISSN (online) 1474-5488
    ISSN 1470-2045
    DOI 10.1016/S1470-2045(19)30071-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Wasm-iCARE: a portable and privacy-preserving web module to build, validate, and apply absolute risk models.

    Balasubramanian, Jeya Balaji / Choudhury, Parichoy Pal / Mukhopadhyay, Srijon / Ahearn, Thomas / Chatterjee, Nilanjan / García-Closas, Montserrat / Almeida, Jonas S

    ArXiv

    2023  

    Abstract: Objective: Absolute risk models estimate an individual's future disease risk over a specified time interval. Applications utilizing server-side risk tooling, such as the R-based iCARE (R-iCARE), to build, validate, and apply absolute risk models, face ... ...

    Abstract Objective: Absolute risk models estimate an individual's future disease risk over a specified time interval. Applications utilizing server-side risk tooling, such as the R-based iCARE (R-iCARE), to build, validate, and apply absolute risk models, face serious limitations in portability and privacy due to their need for circulating user data in remote servers for operation. Our objective was to overcome these limitations.
    Materials and methods: We refactored R-iCARE into a Python package (Py-iCARE) then compiled it to WebAssembly (Wasm-iCARE): a portable web module, which operates entirely within the privacy of the user's device.
    Results: We showcase the portability and privacy of Wasm-iCARE through two applications: for researchers to statistically validate risk models, and to deliver them to end-users. Both applications run entirely on the client-side, requiring no downloads or installations, and keeps user data on-device during risk calculation.
    Conclusions: Wasm-iCARE fosters accessible and privacy-preserving risk tools, accelerating their validation and delivery.
    Language English
    Publishing date 2023-10-13
    Publishing country United States
    Document type Preprint
    ISSN 2331-8422
    ISSN (online) 2331-8422
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Potential utility of risk stratification for multicancer screening with liquid biopsy tests.

    Kim, Elle S / Scharpf, Robert B / Garcia-Closas, Montserrat / Visvanathan, Kala / Velculescu, Victor E / Chatterjee, Nilanjan

    NPJ precision oncology

    2023  Volume 7, Issue 1, Page(s) 39

    Abstract: Our proof-of-concept study reveals the potential of risk stratification by the combined effects of age, polygenic risk scores (PRS), and non-genetic risk factors in increasing the risk-benefit balance of rapidly emerging non-invasive multicancer early ... ...

    Abstract Our proof-of-concept study reveals the potential of risk stratification by the combined effects of age, polygenic risk scores (PRS), and non-genetic risk factors in increasing the risk-benefit balance of rapidly emerging non-invasive multicancer early detection (MCED) liquid biopsy tests. We develop and validate sex-specific pan-cancer risk scores (PCRSs), defined by the combination of body mass index, smoking, family history of cancers, and cancer-specific polygenic risk scores (PRSs), to predict the absolute risk of developing at least one of the many common cancer types. We demonstrate the added value of PRSs in improving the predictive performance of the risk factors only model and project the positive and negative predictive values for two promising multicancer screening tests across risk strata defined by age and PCRS.
    Language English
    Publishing date 2023-04-22
    Publishing country England
    Document type Journal Article
    ISSN 2397-768X
    ISSN 2397-768X
    DOI 10.1038/s41698-023-00377-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Interpretable, non-mechanistic forecasting using empirical dynamic modeling and interactive visualization.

    Mason, Lee / Berrington de Gonzalez, Amy / Garcia-Closas, Montserrat / Chanock, Stephen J / Hicks, Blànaid / Almeida, Jonas S

    PloS one

    2023  Volume 18, Issue 4, Page(s) e0277149

    Abstract: Forecasting methods are notoriously difficult to interpret, particularly when the relationship between the data and the resulting forecasts is not obvious. Interpretability is an important property of a forecasting method because it allows the user to ... ...

    Abstract Forecasting methods are notoriously difficult to interpret, particularly when the relationship between the data and the resulting forecasts is not obvious. Interpretability is an important property of a forecasting method because it allows the user to complement the forecasts with their own knowledge, a process which leads to more applicable results. In general, mechanistic methods are more interpretable than non-mechanistic methods, but they require explicit knowledge of the underlying dynamics. In this paper, we introduce EpiForecast, a tool which performs interpretable, non-mechanistic forecasts using interactive visualization and a simple, data-focused forecasting technique based on empirical dynamic modelling. EpiForecast's primary feature is a four-plot interactive dashboard which displays a variety of information to help the user understand how the forecasts are generated. In addition to point forecasts, the tool produces distributional forecasts using a kernel density estimation method-these are visualized using color gradients to produce a quick, intuitive visual summary of the estimated future. To ensure the work is FAIR and privacy is ensured, we have released the tool as an entirely in-browser web-application.
    Language English
    Publishing date 2023-04-03
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0277149
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: The sequence kernel association test for multicategorical outcomes.

    Jiang, Zhiwen / Zhang, Haoyu / Ahearn, Thomas U / Garcia-Closas, Montserrat / Chatterjee, Nilanjan / Zhu, Hongtu / Zhan, Xiang / Zhao, Ni

    Genetic epidemiology

    2023  Volume 47, Issue 6, Page(s) 432–449

    Abstract: Disease heterogeneity is ubiquitous in biomedical and clinical studies. In genetic studies, researchers are increasingly interested in understanding the distinct genetic underpinning of subtypes of diseases. However, existing set-based analysis methods ... ...

    Abstract Disease heterogeneity is ubiquitous in biomedical and clinical studies. In genetic studies, researchers are increasingly interested in understanding the distinct genetic underpinning of subtypes of diseases. However, existing set-based analysis methods for genome-wide association studies are either inadequate or inefficient to handle such multicategorical outcomes. In this paper, we proposed a novel set-based association analysis method, sequence kernel association test (SKAT)-MC, the sequence kernel association test for multicategorical outcomes (nominal or ordinal), which jointly evaluates the relationship between a set of variants (common and rare) and disease subtypes. Through comprehensive simulation studies, we showed that SKAT-MC effectively preserves the nominal type I error rate while substantially increases the statistical power compared to existing methods under various scenarios. We applied SKAT-MC to the Polish breast cancer study (PBCS), and identified gene FGFR2 was significantly associated with estrogen receptor (ER)+ and ER- breast cancer subtypes. We also investigated educational attainment using UK Biobank data (
    MeSH term(s) Humans ; Female ; Genome-Wide Association Study ; Genetic Variation ; Models, Genetic ; Computer Simulation ; Breast Neoplasms/genetics
    Language English
    Publishing date 2023-04-19
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 605785-8
    ISSN 1098-2272 ; 0741-0395
    ISSN (online) 1098-2272
    ISSN 0741-0395
    DOI 10.1002/gepi.22527
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Book ; Online: A FAIR platform for reproducing mutational signature detection on tumor sequencing data

    Ge, Aaron / Zhang, Tongwu / Bodelon, Clara / Garcia-Closas, Montserrat / Almeida, Jonas / Balasubramanian, Jeya

    2023  

    Abstract: This paper presents a portable, privacy-preserving, in-browser platform for the reproducible assessment of mutational signature detection methods from sparse sequencing data generated by targeted gene panels. The platform aims to address the ... ...

    Abstract This paper presents a portable, privacy-preserving, in-browser platform for the reproducible assessment of mutational signature detection methods from sparse sequencing data generated by targeted gene panels. The platform aims to address the reproducibility challenges in mutational signature research by adhering to the FAIR principles, making it findable, accessible, interoperable, and reusable. Our approach focuses on the detection of specific mutational signatures, such as SBS3, which have been linked to specific mutagenic processes. The platform relies on publicly available data, simulation, downsampling techniques, and machine learning algorithms to generate training data and labels and to train and evaluate models. The key achievement of our platform is its transparency, reusability, and privacy preservation, enabling researchers and clinicians to analyze mutational signatures with the guarantee that no data circulates outside the client machine.

    Comment: Our proposed in-browser platform is publicly available under the MIT license at https://aaronge-2020.github.io/Sig3-Detection/. No data leaves this privacy-preserving environment, which can be cloned or forked and served from other domains with no restrictions. All the code and relevant data used to create this platform can be found at https://github.com/aaronge-2020/Sig3-Detection
    Keywords Quantitative Biology - Genomics
    Subject code 005
    Publishing date 2023-06-02
    Publishing country us
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Toward Risk-Stratified Breast Cancer Screening: Considerations for Changes in Screening Guidelines.

    Gierach, Gretchen L / Choudhury, Parichoy Pal / García-Closas, Montserrat

    JAMA oncology

    2019  Volume 6, Issue 1, Page(s) 31–33

    MeSH term(s) Breast Neoplasms/diagnosis ; Breast Neoplasms/epidemiology ; Early Detection of Cancer/standards ; Female ; Humans ; Mammography ; Mass Screening
    Language English
    Publishing date 2019-11-16
    Publishing country United States
    Document type Editorial ; Comment
    ISSN 2374-2445
    ISSN (online) 2374-2445
    DOI 10.1001/jamaoncol.2019.3820
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: The case for increasing diversity in tissue-based functional genomics datasets to understand human disease susceptibility.

    Long, Erping / García-Closas, Montserrat / Chanock, Stephen J / Camargo, M Constanza / Banovich, Nicholas E / Choi, Jiyeon

    Nature communications

    2022  Volume 13, Issue 1, Page(s) 2907

    MeSH term(s) Disease Susceptibility ; Genetic Variation ; Genomics ; Humans
    Language English
    Publishing date 2022-05-25
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Intramural
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-022-30650-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Book ; Online: Wasm-iCARE

    Balasubramanian, Jeya Balaji / Choudhury, Parichoy Pal / Mukhopadhyay, Srijon / Ahearn, Thomas / Chatterjee, Nilanjan / García-Closas, Montserrat / Almeida, Jonas S.

    a portable and privacy-preserving web module to build, validate, and apply absolute risk models

    2023  

    Abstract: Objective: Absolute risk models estimate an individual's future disease risk over a specified time interval. Applications utilizing server-side risk tooling, such as the R-based iCARE (R-iCARE), to build, validate, and apply absolute risk models, face ... ...

    Abstract Objective: Absolute risk models estimate an individual's future disease risk over a specified time interval. Applications utilizing server-side risk tooling, such as the R-based iCARE (R-iCARE), to build, validate, and apply absolute risk models, face serious limitations in portability and privacy due to their need for circulating user data in remote servers for operation. Our objective was to overcome these limitations. Materials and Methods: We refactored R-iCARE into a Python package (Py-iCARE) then compiled it to WebAssembly (Wasm-iCARE): a portable web module, which operates entirely within the privacy of the user's device. Results: We showcase the portability and privacy of Wasm-iCARE through two applications: for researchers to statistically validate risk models, and to deliver them to end-users. Both applications run entirely on the client-side, requiring no downloads or installations, and keeps user data on-device during risk calculation. Conclusions: Wasm-iCARE fosters accessible and privacy-preserving risk tools, accelerating their validation and delivery.

    Comment: 10 pages, 2 figures
    Keywords Quantitative Biology - Quantitative Methods
    Subject code 005 ; 330
    Publishing date 2023-10-13
    Publishing country us
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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