{"doi":"10.1038/s41416-025-03159-2","title":"Prospective study of circulating metabolomic profiles and breast cancer incidence among predominantly premenopausal women","abstract":"BACKGROUND: Associations between premenopausal plasma metabolites and breast cancer incidence are largely unknown. METHODS: We conducted a prospective, matched case-control study in which we measured pre-diagnostic metabolomic profiles among predominantly premenopausal women in the Nurses' Health Study II (n = 2010). Lipids, carbohydrates, and organic acid-related metabolites (n = 218) were profiled via liquid chromatography-tandem mass spectrometry. Conditional logistic regression was used to estimate odds ratios (OR) for associations between individual metabolites and breast cancer incidence. Associations with metabolite groups were assessed using metabolite set enrichment analysis (MSEA). RESULTS: Six individual lipid-related metabolites were nominally associated with breast cancer incidence (taurodeoxycholate [OR for per 1 standard deviation increase in metabolite level = 1.15, 95% CI = 1.04-1.28]; C16:1 cholesteryl ester [OR = 0.88, 95% CI = 0.79-0.97]; three phosphocholine (PC)-related metabolites, C34:1 PC [OR = 0.87, 95% CI = 0.78-0.98], C34:3 PC [OR = 0.88, 95% CI = 0.79-0.98], C32:1 PC [OR = 0.88, 95% CI = 0.79-0.98]; indoxyl sulfate [OR = 0.90, 95% CI = 0.82-1.00]). In MSEA analyses, triglycerides (TAGs) with <3 double bonds (normalized enrichment score (NES) = -2.54) and PCs (NES = -2.12) were inversely associated with breast cancer incidence overall and across subgroups. Phosphatidylethanolamine (PE) plasmalogens (NES = 1.83) and PC plasmalogens (NES = 2.23) were positively associated with breast cancer incidence. CONCLUSIONS: Premenopausal plasma TAGs, PCs, and plasmalogen metabolites were associated with breast cancer incidence. Further validation in independent cohorts is warranted.","journal":"British Journal of Cancer","year":2025,"id":574174,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":0.0,"corpus_rank":10062,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":true,"is_dataset_confidence":0.581,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":4.1667,"fair_percentile":4.891470498318557,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":352538,"name":"Oana A. Zeleznik","orcid":"0000-0002-8705-1163","position":1,"is_corresponding":false},{"id":370676,"name":"Emma E. McGee","orcid":"0000-0002-7456-6408","position":2,"is_corresponding":false},{"id":612735,"name":"Kristen D. Brantley","orcid":"0000-0003-0084-4775","position":3,"is_corresponding":false},{"id":537829,"name":"Raji Balasubramanian","orcid":"0000-0002-1488-1692","position":4,"is_corresponding":false},{"id":246330,"name":"Bernard Rosner","orcid":"0000-0001-6907-0056","position":5,"is_corresponding":false},{"id":104570,"name":"Walter C. Willett","orcid":"0000-0003-1458-7597","position":6,"is_corresponding":false},{"id":6941,"name":"Julián Ávila-Pacheco","orcid":"0000-0001-9388-3946","position":7,"is_corresponding":false},{"id":6946,"name":"Clary B. Clish","orcid":"0000-0001-8259-9245","position":8,"is_corresponding":false},{"id":104571,"name":"A. Heather Eliassen","orcid":"0000-0002-3961-6609","position":9,"is_corresponding":false},{"id":519542,"name":"Tengteng Wang","orcid":"0000-0001-9001-186X","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-19T02:57:40.686992Z","pmid":"40908295","pmcid":"PMC12572396","fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":11.1111,"fair_a":31.25,"fair_i":0.0,"fair_r":16.6667,"fair_zscore":-1.1986,"fair_rationale":{"fair_score":4.17,"has_llm":true,"taxonomy_version":"fair_taxonomy_v5","dimensions":{"F":{"name":"Findable","score":11.11,"criteria":[{"key":"f_dataset_pid","label":"Persistent identifier for the data","kind":"llm","weight":2.0,"fraction":0.0,"verdict":"no","evidence":"https://www.nurseshealthstudy.org/researchers","grounded":false,"rationale":"The paper provides a web address (URL) for accessing the data, which is not a persistent identifier scheme (DOI, Handle, ARK, or repository accession). [downgraded to 'no' — no verifiable quote from the paper] [majority verdict 'no' (4/5 passes agreed)]","anchors":["RDA-F1-01D — FAIR Data Maturity Model: 'Data is identified by a persistent identifier' (priorit","RDA-F1-02D — FAIR Data Maturity Model: 'Data is identified by a globally unique identifier'","FsF-F1-02D — F-UJI/FAIRsFAIR: 'Data is assigned a persistent identifier'"],"scored":true,"signal":null},{"key":"f_repository_named","label":"Named repository","kind":"llm","weight":2.0,"fraction":0.0,"verdict":"no","evidence":"Investigators interested in accessing NHSII data may submit a research proposal to the data access committee via the Nurses’ Health Study website ( https://www.nurseshealthstudy.org/researchers )","grounded":false,"rationale":"The named holder is the Nurses' Health Study website, a project/cohort website, not a standard data repository from re3data/FAIRsharing. [downgraded to 'no' — no verifiable quote from the paper] [majority verdict 'no' (3/5 passes agreed)]","anchors":["RDA-F4-01M — FAIR Data Maturity Model: metadata is offered so it can be harvested and indexed (","NIH DMS Policy Element 4 (NOT-OD-21-014) — name the repository where data will be archived","NSTC Desirable Characteristics of Data Repositories (2022) — 'Long-Term Sustainability', 'Reten"],"scored":true,"signal":null},{"key":"f_data_availability_statement","label":"Data-availability statement","kind":"llm","weight":2.0,"fraction":0.0,"verdict":"no","evidence":"Due to participant privacy and data use agreements, our study data are not publicly available. 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[downgraded to 'no' — no verifiable quote from the paper] [majority verdict 'no' (4/5 passes agreed)]","anchors":["Colavizza, Hrynaszkiewicz, Staden, Whitaker & McGillivray (2020), 'The citation advantage of li","Springer Nature research data policy — Data Availability Statements: standard statement templat","RDA-F3-01M — metadata clearly and explicitly includes the identifier of the data it describes"],"scored":false,"signal":null},{"key":"f_discovery_metadata","label":"Description of the dataset as an object","kind":"llm","weight":2.0,"fraction":0.5,"verdict":"partial","evidence":"In total, 218 metabolites (C8-positive = 177; HILIC-negative = 41) were included in the primary analysis.","grounded":true,"rationale":"The dataset's content is described in running prose only, without an itemised inventory section, table, or list of files/variables. 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[downgraded to 'no' — no verifiable quote from the paper] [majority verdict 'no' (4/5 passes agreed)]","anchors":["RDA-A1.1-01D — 'Data is accessible through a free access protocol'","FsF-A1-01M — F-UJI: 'Metadata contains access level and access conditions of the data'","NSTC Desirable Characteristics of Data Repositories (2022) — 'Free and Easy Access'"],"scored":true,"signal":null},{"key":"a_access_conditions_stated","label":"Access level labelled","kind":"llm","weight":1.0,"fraction":1.0,"verdict":"yes","evidence":"Due to participant privacy and data use agreements, our study data are not publicly available.","grounded":true,"rationale":"The paper directly states that the study data are not publicly available, which constitutes an explicit access-level label. [majority verdict 'yes' (4/5 passes agreed)]","anchors":["FsF-A1-01M — F-UJI: 'Metadata contains access level and access conditions of the data'","RDA-A1-01M — metadata contains information to enable the user to get access to the data","COAR Controlled Vocabularies — Access Rights v1.0 (open / embargoed / restricted / metadata-onl"],"scored":false,"signal":null},{"key":"a_controlled_access_for_sensitive","label":"Gatekeeper for sensitive data","kind":"llm","weight":0.5,"fraction":0.5,"verdict":"partial","evidence":"submit a research proposal to the data access committee via the Nurses’ Health Study website ( https://www.nurseshealthstudy.org/researchers )","grounded":false,"rationale":"The paper names an institutional gatekeeper (data access committee) for the sensitive human-subject data. [downgraded to 'partial' — no verifiable quote from the paper] [majority verdict 'partial' (3/5 passes agreed)]","anchors":["NIH Genomic Data Sharing Policy (NOT-OD-14-124) — controlled-access via a Data Access Committee","RDA-A1.2-01D — 'Data is accessible through an access protocol that supports authentication and ","NIH DMS Policy Element 5 (NOT-OD-21-014) — Access, Distribution, or Reuse Considerations (conse"],"scored":false,"signal":null},{"key":"a_timeline_retention","label":"Availability timing & retention","kind":"llm","weight":0.5,"fraction":0.0,"verdict":"no","evidence":null,"grounded":false,"rationale":"No sentence in the paper addresses how long this study's data will remain available or any persistence commitment.","anchors":["NIH DMS Plan Element 4 (NOT-OD-21-014) — Data Preservation, Access, and Associated Timelines","NSTC Desirable Characteristics (2022), Organizational Infrastructure: 'Retention Policy'","RDA-A2-01M — 'Metadata is guaranteed to remain available after data is no longer available'"],"scored":false,"signal":null}]},"I":{"name":"Interoperable","score":0.0,"criteria":[{"key":"i_open_nonproprietary_format","label":"Open file format","kind":"llm","weight":1.0,"fraction":0.0,"verdict":"no","evidence":null,"grounded":false,"rationale":"No file format for the released data is named in the paper.","anchors":["FsF-R1.3-02D — F-UJI: 'Data is available in a file format recommended by the target research co","RDA-R1.3-02D — data is expressed in a machine-understandable community standard","RDA-I1-01D — data uses a knowledge representation expressed in a standardised format"],"scored":true,"signal":null},{"key":"i_community_standard_vocabulary","label":"Community standard / vocabulary","kind":"llm","weight":1.0,"fraction":0.0,"verdict":"no","evidence":null,"grounded":false,"rationale":"No data or metadata community standard (e.g., MIAME, BIDS, GO) is named in the paper; only analysis methods are mentioned.","anchors":["RDA-R1.3-01M — 'Metadata complies with a community standard' (priority Essential)","RDA-R1.3-01D — 'Data complies with a community standard'","RDA-I2-01M — '(Meta)data use vocabularies that follow FAIR principles'"],"scored":false,"signal":null},{"key":"i_qualified_references","label":"Identifiers for the resources the data depend on","kind":"llm","weight":0.5,"fraction":0.0,"verdict":"no","evidence":null,"grounded":false,"rationale":"No identifier for an external resource (e.g., another dataset, reference genome, or database) is provided in the text. [majority verdict 'no' (4/5 passes agreed)]","anchors":["RDA-I3-01M — '(meta)data include references to other (meta)data'","RDA-I3-03M — 'metadata includes qualified references to other metadata'","FsF-I3-01M — F-UJI: 'Metadata includes links between the data and its related entities'"],"scored":false,"signal":null}]},"R":{"name":"Reusable","score":16.67,"criteria":[{"key":"r_reuse_license","label":"Reuse licence","kind":"llm","weight":2.0,"fraction":0.0,"verdict":"no","evidence":null,"grounded":false,"rationale":"No licence or terms document is named for the data; the article's CC BY licence applies to the paper, not the data.","anchors":["RDA-R1.1-01M — 'Metadata includes information about the licence under which the data can be reu","RDA-R1.1-02M — 'Metadata refers to a standard reuse licence'","RDA-R1.1-03M — 'Metadata refers to a machine-understandable reuse licence'"],"scored":true,"signal":null},{"key":"r_provenance_methods","label":"Provenance of the data","kind":"llm","weight":1.0,"fraction":0.5,"verdict":"partial","evidence":"Plasma metabolites were profiled at the Broad Institute of MIT and Harvard (Cambridge, MA) using a liquid chromatography-tandem mass spectrometry (LC-MS) method. 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A bare URL is not persistent: it is the single most common cause of a dead data link five years after publication. For proteomics data, deposit in PRIDE (PXD accession) or ProteomeXchange.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":"https://www.nurseshealthstudy.org/researchers","why":"The paper provides a web address (URL) for accessing the data, which is not a persistent identifier scheme (DOI, Handle, ARK, or repository accession). [downgraded to 'no' — no verifiable quote from the paper] [majority verdict 'no' (4/5 passes agreed)]","gain":16.67,"priority":"essential","scored":true},{"key":"f_repository_named","dimension":"F","label":"Named repository","action":"Deposit the data in a repository registered in re3data/FAIRsharing (a domain repository such as GEO, SRA, dbGaP, PRIDE, or a generalist such as Zenodo, Dryad, Dataverse) and name it explicitly in the paper. A lab website is not an archive: it has no retention commitment and no accession. For proteomics data, deposit in PRIDE (PXD accession) or ProteomeXchange.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":"Investigators interested in accessing NHSII data may submit a research proposal to the data access committee via the Nurses’ Health Study website ( https://www.nurseshealthstudy.org/researchers )","why":"The named holder is the Nurses' Health Study website, a project/cohort website, not a standard data repository from re3data/FAIRsharing. [downgraded to 'no' — no verifiable quote from the paper] [majority verdict 'no' (3/5 passes agreed)]","gain":16.67,"priority":"essential","scored":true},{"key":"a_data_openly_accessible","dimension":"A","label":"Access route free of preconditions","action":"Remove the precondition or justify it. Release the data at publication with no embargo, no registration wall, and no approval step — NIH's zero-embargo public- access rule (NOT-OD-25-101) has already made 'available at publication' the federal baseline for the article; the data should not lag behind it. For proteomics data, deposit in PRIDE (PXD accession) or ProteomeXchange.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":"Due to participant privacy and data use agreements, our study data are not publicly available. Investigators interested in accessing NHSII data may submit a research proposal to the data access committee via the Nurses’ Health Study website ( https://www.nurseshealthstudy.org/researchers )","why":"The paper states a precondition (submit a research proposal) for access, which is a specified followable process, not unconditional open access. [downgraded to 'no' — no verifiable quote from the paper] [majority verdict 'no' (4/5 passes agreed)]","gain":16.67,"priority":"essential","scored":true},{"key":"r_reuse_license","dimension":"R","label":"Reuse licence","action":"Attach a standard, machine-readable open licence to the deposit — CC0 or CC BY, which is what Horizon Europe and most funders expect — and print the licence identifier in the paper. 'Free to use' is not a licence: it grants nothing a reuser's institution can rely on.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":null,"why":"No licence or terms document is named for the data; the article's CC BY licence applies to the paper, not the data.","gain":16.67,"priority":"essential","scored":true},{"key":"f_dataset_cited","dimension":"F","label":"Dataset formally cited","action":"Cite the dataset in the reference list like a publication — creator, year, title, repository, DOI/accession — and cite it in-text where it is used. 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[downgraded to 'no' — no verifiable quote from the paper]","gain":8.33,"priority":"important","scored":true},{"key":"i_open_nonproprietary_format","dimension":"I","label":"Open file format","action":"Release the data in an open, community-standard format (CSV/TSV, JSON, HDF5, NetCDF, FASTQ, VCF, NIfTI…) instead of — or alongside — any proprietary or instrument-native format, and name the format in the paper. A dataset that needs a €2,000 licence to open is not reusable. Prefer open proteomics formats such as mzML or mzIdentML.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":null,"why":"No file format for the released data is named in the paper.","gain":8.33,"priority":"important","scored":true},{"key":"x_code_availability","dimension":"R","label":"Analysis code available","action":"Publish the analysis code in a public forge, archive a tagged release with a DOI (Zenodo/Software Heritage), and cite that DOI in the paper. NIH DMS Element 2 asks for the tools and code, not only the data — and 'available on request' is not a locator. Archive the analysis code in a versioned repository (GitHub + a Zenodo release DOI).","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":"The final analytic programs used to generate derived data and study results are systematically documented and archived within the NHS secure intranet environment to ensure reproducibility. 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A reader reproducing your work against 'the current release' is reproducing it against a different dataset.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":null,"why":"No version token or date is given to identify a specific snapshot of the dataset.","gain":4.17,"priority":"useful","scored":true},{"key":"f_data_availability_statement","dimension":"F","label":"Data-availability statement","action":"Replace the statement with the repository template: name the repository and give the accession or DOI (Colavizza category 3). This is the only DAS class associated with a measured citation advantage; 'available on reasonable request' and 'within the article' are not.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":"Due to participant privacy and data use agreements, our study data are not publicly available. 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Describe the dataset as an object in its own right, not as a by-product of the findings — this is what makes it discoverable to someone who is not looking for your paper.","anchors":["yes","partial","no"],"verdict":"partial","current":0.5,"evidence":"In total, 218 metabolites (C8-positive = 177; HILIC-negative = 41) were included in the primary analysis.","why":"The dataset's content is described in running prose only, without an itemised inventory section, table, or list of files/variables. [majority verdict 'partial' (4/5 passes agreed)]","gain":0.0,"priority":"essential","scored":false},{"key":"i_community_standard_vocabulary","dimension":"I","label":"Community standard / vocabulary","action":"Adopt and NAME your domain's data standard — the minimum-information checklist, metadata schema, or ontology your community uses (MIAME/MINSEQE, ISA-Tab, BIDS, an OBO ontology, HL7 FHIR/OMOP) — and say which one you followed. A reporting checklist standardises your paper; it does nothing for your data. In proteomics, describe the data with mzML or MIAPE.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":null,"why":"No data or metadata community standard (e.g., MIAME, BIDS, GO) is named in the paper; only analysis methods are mentioned.","gain":0.0,"priority":"important","scored":false},{"key":"r_provenance_methods","dimension":"R","label":"Provenance of the data","action":"Name the instruments, kits, and software — with versions — that produced the data, not just the verbs. 'Reads were aligned' is not provenance; 'aligned with STAR v2.7.9a to GRCh38' is, because someone else can rerun it.","anchors":["yes","partial","no"],"verdict":"partial","current":0.5,"evidence":"Plasma metabolites were profiled at the Broad Institute of MIT and Harvard (Cambridge, MA) using a liquid chromatography-tandem mass spectrometry (LC-MS) method. Briefly, for the C8-positive platform, plasma lipids were profiled using a Nexera X2 U-HPLC (Shimadzu Corp.; Marlborough, MA) coupled to a Q Exactive Plus mass spectrometer (Thermo Fisher Scientific; Waltham, MA).","why":"The paper names specific instruments, platforms, and software (Nexera X2 U-HPLC, Q Exactive Plus mass spectrometer) used to produce the data. [downgraded to 'partial' — no verifiable quote from the paper]","gain":0.0,"priority":"important","scored":false},{"key":"r_documentation_codebook","dimension":"R","label":"Documentation / codebook","action":"Ship a README and a data dictionary IN the deposit — every file, every variable, its units, its allowed values, its missing-value codes. It is the cheapest single thing that makes a dataset usable by someone who was not in the lab, and a table buried in the article does not travel with the data.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":null,"why":"No documentation object (README, data dictionary, codebook) is mentioned as accompanying the data, nor is a variable-definition table provided inside the article for the metabolomic data. [majority verdict 'no' (4/5 passes agreed)]","gain":0.0,"priority":"important","scored":false},{"key":"a_controlled_access_for_sensitive","dimension":"A","label":"Gatekeeper for sensitive data","action":"Route sensitive data through an institutional gatekeeper — deposit in a controlled- access repository (dbGaP, EGA) with a Data Access Committee and a published DUA — rather than through the corresponding author's inbox. An author-gated dataset dies with the author's email address, and 'on reasonable request' has been shown repeatedly not to yield data.","anchors":["yes","partial","no"],"verdict":"partial","current":0.5,"evidence":"submit a research proposal to the data access committee via the Nurses’ Health Study website ( https://www.nurseshealthstudy.org/researchers )","why":"The paper names an institutional gatekeeper (data access committee) for the sensitive human-subject data. [downgraded to 'partial' — no verifiable quote from the paper] [majority verdict 'partial' (3/5 passes agreed)]","gain":0.0,"priority":"useful","scored":false},{"key":"i_qualified_references","dimension":"I","label":"Identifiers for the resources the data depend on","action":"Cite by identifier every resource the data depend on — the source datasets' accessions, the reference build (GRCh38 / GCA_000001405.28), the cohort application number, the code DOI — and register those relations on the dataset record (IsDerivedFrom, IsSupplementTo). A name is not a link: it cannot be resolved, versioned, or followed by a machine.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":null,"why":"No identifier for an external resource (e.g., another dataset, reference genome, or database) is provided in the text. [majority verdict 'no' (4/5 passes agreed)]","gain":0.0,"priority":"useful","scored":false},{"key":"a_timeline_retention","dimension":"A","label":"Availability timing & retention","action":"State when the data become available AND how long they will be retained — cite the repository's preservation policy. NIH DMS Element 4 asks for both; most papers give neither.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":null,"why":"No sentence in the paper addresses how long this study's data will remain available or any persistence commitment.","gain":0.0,"priority":"useful","scored":false}],"suggestions":["Mint or cite a persistent identifier for the dataset — a repository DOI or an accession from a registered repository — and print it in the paper. A bare URL is not persistent: it is the single most common cause of a dead data link five years after publication. For proteomics data, deposit in PRIDE (PXD accession) or ProteomeXchange.","Deposit the data in a repository registered in re3data/FAIRsharing (a domain repository such as GEO, SRA, dbGaP, PRIDE, or a generalist such as Zenodo, Dryad, Dataverse) and name it explicitly in the paper. A lab website is not an archive: it has no retention commitment and no accession. For proteomics data, deposit in PRIDE (PXD accession) or ProteomeXchange.","Remove the precondition or justify it. Release the data at publication with no embargo, no registration wall, and no approval step — NIH's zero-embargo public- access rule (NOT-OD-25-101) has already made 'available at publication' the federal baseline for the article; the data should not lag behind it. For proteomics data, deposit in PRIDE (PXD accession) or ProteomeXchange.","Attach a standard, machine-readable open licence to the deposit — CC0 or CC BY, which is what Horizon Europe and most funders expect — and print the licence identifier in the paper. 'Free to use' is not a licence: it grants nothing a reuser's institution can rely on.","Cite the dataset in the reference list like a publication — creator, year, title, repository, DOI/accession — and cite it in-text where it is used. Only a reference- list entry is machine-readable to Crossref/DataCite, and only a citation lets the data earn credit. Cite the proteomics repository accession (e.g. from PRIDE (PXD accession) or ProteomeXchange) in the reference list."],"model":"deepseek/deepseek-v4-flash","agent_version":"fair_agent_v8","fulltext_source":"unpaywall_pdf"},"fair_model":"deepseek/deepseek-v4-flash","fair_agent_version":"fair_agent_v8","fair_fulltext_source":"unpaywall_pdf","fair_has_llm":true,"fair_computed_at":"2026-07-20T13:58:45.115216Z","clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}