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Circulating vitamin D and breast cancer risk: an international pooling project of 17 cohorts
Departments of Epidemiology and Oncology, Johns Hopkins Bloomberg School of Public Health and Kimmel Cancer Center, MD, Baltimore, United States.
Department of Epidemiology, University of Michigan School of Public Health, MI, Ann Arbor, United States.
Departments of Population Health and Environmental Medicine, New York University Grossman School of Medicine, NY, New York, United States.
Department of Biostatistics, Harvard T.H. Chan School of Public Health, MA, Boston, United States; Department of Epidemiology, Harvard T.H. Chan School of Public Health, MA, Boston, United States; Channing Division of Network Medicine, Department of Medicine, Harvard Medical School, MA, Boston, United States.
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2023 (English)In: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 38, p. 11-29Article in journal (Refereed) Published
Abstract [en]

Laboratory and animal research support a protective role for vitamin D in breast carcinogenesis, but epidemiologic studies have been inconclusive. To examine comprehensively the relationship of circulating 25-hydroxyvitamin D [25(OH)D] to subsequent breast cancer incidence, we harmonized and pooled participant-level data from 10 U.S. and 7 European prospective cohorts. Included were 10,484 invasive breast cancer cases and 12,953 matched controls. Median age (interdecile range) was 57 (42–68) years at blood collection and 63 (49–75) years at breast cancer diagnosis. Prediagnostic circulating 25(OH)D was either newly measured using a widely accepted immunoassay and laboratory or, if previously measured by the cohort, calibrated to this assay to permit using a common metric. Study-specific relative risks (RRs) for season-standardized 25(OH)D concentrations were estimated by conditional logistic regression and combined by random-effects models. Circulating 25(OH)D increased from a median of 22.6 nmol/L in consortium-wide decile 1 to 93.2 nmol/L in decile 10. Breast cancer risk in each decile was not statistically significantly different from risk in decile 5 in models adjusted for breast cancer risk factors, and no trend was apparent (P-trend = 0.64). Compared to women with sufficient 25(OH)D based on Institute of Medicine guidelines (50– < 62.5 nmol/L), RRs were not statistically significantly different at either low concentrations (< 20 nmol/L, 3% of controls) or high concentrations (100– < 125 nmol/L, 3% of controls; ≥ 125 nmol/L, 0.7% of controls). RR per 25 nmol/L increase in 25(OH)D was 0.99 [95% confidence intervaI (CI) 0.95–1.03]. Associations remained null across subgroups, including those defined by body mass index, physical activity, latitude, and season of blood collection. Although none of the associations by tumor characteristics reached statistical significance, suggestive inverse associations were seen for distant and triple negative tumors. Circulating 25(OH)D, comparably measured in 17 international cohorts and season-standardized, was not related to subsequent incidence of invasive breast cancer over a broad range in vitamin D status.

Place, publisher, year, edition, pages
Springer Science+Business Media B.V., 2023. Vol. 38, p. 11-29
Keywords [en]
25-Hydroxyvitamin D, Biomarker, Breast cancer, Calibration, Pooled analysis, Prospective cohort study, Vitamin D
National Category
Cancer and Oncology Public Health, Global Health and Social Medicine
Identifiers
URN: urn:nbn:se:umu:diva-202341DOI: 10.1007/s10654-022-00921-1ISI: 000908100600003Scopus ID: 2-s2.0-85145419390OAI: oai:DiVA.org:umu-202341DiVA, id: diva2:1725897
Funder
Swedish Cancer SocietySwedish Research CouncilRegion VästerbottenAvailable from: 2023-01-12 Created: 2023-01-12 Last updated: 2025-02-20Bibliographically approved

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Hallmans, GöranSund, Malin

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Department of Public Health and Clinical MedicineDepartment of Surgical and Perioperative Sciences
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