Karina Dalsgaard Sørensen

Circulating vitamin D concentrations and risk of breast and prostate cancer: a Mendelian randomization study

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

DOI

  • Xia Jiang, Cardiovascular Epidemiology Unit, Department of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
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  • Niki L Dimou, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, 45110 Ioannina, Greece. ktsilidis@gmail.com.
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  • Kawthar Al-Dabhani, Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, W2 1NY London, UK.
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  • Sarah J Lewis, MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.
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  • Richard M Martin, National Institute for Health Research (NIHR) Bristol Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust and the University of Bristol, Bristol, UK.
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  • Philip C Haycock, MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.
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  • Marc J Gunter, Nutritional Epidemiology Group, Section of Nutrition and Metabolism, International Agency for Research On Cancer (IARC-WHO), Lyon, France.
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  • Timothy J Key, Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
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  • Rosalind A Eeles, Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, London, United Kingdom.
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  • Kenneth Muir, Institute of Population Health, University of Manchester, Manchester, England.
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  • David Neal, Department of Oncology, University of Cambridge, Cambridge, United Kingdom.
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  • Graham G Giles, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
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  • Edward L Giovannucci, Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
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  • Meir Stampfer, Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
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  • Brandon L Pierce, Department of Human Genetics, The University of Chicago, Chicago, IL, USA.
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  • Joellen M Schildkraut, Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA.
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  • Shaneda Warren Andersen, Vanderbilt Genetics Institute, Division of Epidemiology, Institute of Medicine and Public Health, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37203, USA.
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  • Deborah Thompson, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, United Kingdom.
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  • Wei Zheng, Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37203, USA.
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  • Peter Kraft, Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
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  • Konstantinos K Tsilidis, Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, W2 1NY London, UK.
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  • PRACTICAL, CRUK, BPC3, CAPS and PEGASUS consortia

BACKGROUND: Observational studies have suggested an association between circulating vitamin D concentrations [25(OH)D] and risk of breast and prostate cancer, which was not supported by a recent Mendelian randomization (MR) analysis comprising 15 748 breast and 22 898 prostate-cancer cases. Demonstrating causality has proven challenging and one common limitation of MR studies is insufficient power.

METHODS: We aimed to determine whether circulating concentrations of vitamin D are causally associated with the risk of breast and prostate cancer, by using summary-level data from the largest ever genome-wide association studies conducted on vitamin D (N = 73 699), breast cancer (Ncase = 122 977) and prostate cancer (Ncase = 79 148). We constructed a stronger instrument using six common genetic variants (compared with the previous four variants) and applied several two-sample MR methods.

RESULTS: We found no evidence to support a causal association between 25(OH)D and risk of breast cancer [OR per 25 nmol/L increase, 1.02 (95% confidence interval: 0.97-1.08), P = 0.47], oestrogen receptor (ER)+ [1.00 (0.94-1.07), P = 0.99] or ER- [1.02 (0.90-1.16), P = 0.75] subsets, prostate cancer [1.00 (0.93-1.07), P = 0.99] or the advanced subtype [1.02 (0.90-1.16), P = 0.72] using the inverse-variance-weighted method. Sensitivity analyses did not reveal any sign of directional pleiotropy.

CONCLUSIONS: Despite its almost five-fold augmented sample size and substantially improved statistical power, our MR analysis does not support a causal effect of circulating 25(OH)D concentrations on breast- or prostate-cancer risk. However, we can still not exclude a modest or non-linear effect of vitamin D. Future studies may be designed to understand the effect of vitamin D in subpopulations with a profound deficiency.

Original languageEnglish
JournalInternational Journal of Epidemiology
Volume48
Issue5
Pages (from-to)1416-1424
Number of pages9
ISSN0300-5771
DOIs
Publication statusPublished - 1 Oct 2019

    Research areas

  • Aged, Breast Neoplasms/epidemiology, Causality, Female, Genome-Wide Association Study, Humans, Male, Mendelian Randomization Analysis, Middle Aged, Polymorphism, Single Nucleotide, Prostatic Neoplasms/epidemiology, Receptors, Estrogen/biosynthesis, Risk Factors, Vitamin D/blood

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