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Relationship of very low serum 25-hydroxyvitamin D3 levels with long-term survival in a large cohort of colorectal cancer patients from Germany

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Abstract

To investigate the association of serum 25-hydroxyvitamin D (25(OH)D3) with survival in a large prospective cohort study of colorectal cancer (CRC) patients. The study population consisted of 2,910 patients diagnosed with CRC between 2003 and 2010 who participated in the DACHS study, a multicenter study from Germany with comprehensive long-term follow-up. 25(OH)D3 was determined in serum samples collected shortly after cancer diagnosis by High Performance Liquid Chromatography-Electro Spray Ionization-Mass Spectrometry. Analyses of survival outcomes were performed using Cox regression with comprehensive adjustment for relevant confounders. The majority (59%) of CRC patients were vitamin D deficient (serum 25(OH)D3 levels <30 nmol/L). During a median follow-up of 4.8 years, 787 deaths occurred, 573 of which were due to CRC. Compared to patients in the highest 25(OH)D3 quintile (>45.20 nmol/L), those in the lowest 25(OH)D3 quintile (<11.83 nmol/L) had a strongly increased mortality. Adjusted hazard ratios (95% Confidence Interval) were 1.78 (1.39–2.27), 1.65 (1.24–2.21), 1.32 (1.03–1.71) and 1.48 (1.18–1.85) for all-cause mortality, CRC-specific mortality, recurrence-free and disease-free survival, respectively. Subgroup analyses did not show any significant effect modification across strata defined by sex, age, stage, body mass index, or the late entry. Dose–response analyses showed a strong inverse relationship between serum 25(OH)D3 levels and survival endpoints at 25(OH)D3 levels <30 nmol/L, and no association with mortality at higher 25(OH)D3 levels. Vitamin D deficiency is highly prevalent in CRC patients and a strong independent predictor of poor prognosis. The possibility of enhancing CRC prognosis by vitamin D supplementation, ideally combined with outdoor physical activity, should be evaluated by randomized controlled trials focusing on patients with vitamin D deficiency.

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Acknowledgements

This work was supported by the German Research Council (BR 1704/6-1, BR 1704/6-3, BR 1704/6-4, CH 117/1-1, HO 5117/2-1), the German Federal Ministry of Education and Research (01KH0404 and 01ER0814), the Interdisciplinary Research Program of the National Center for Tumor Diseases, Germany, and the Klaus Tschira Foundation.

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Authors and Affiliations

  1. Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120, Heidelberg, Germany

    Haifa Maalmi, Viola Walter, Lina Jansen, Ben Schöttker, Michael Hoffmeister & Hermann Brenner

  2. Network Aging Research (NAR), Heidelberg University, Bergheimer Strasse 20, 69115, Heidelberg, Germany

    Haifa Maalmi, Ben Schöttker & Hermann Brenner

  3. Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120, Heidelberg, Germany

    Jenny Chang-Claude

  4. Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Im Neuenheimer Feld 460, 69120, Heidelberg, Germany

    Robert W. Owen & Hermann Brenner

  5. Departments of General, Visceral and Transplantation Surgery, University Hospital, Im Neuenheimer Feld 110, Heidelberg, Germany

    Alexis Ulrich

  6. Institute of Health Care and Social Sciences, FOM University, Essen, Germany

    Ben Schöttker

  7. German Cancer Consortium, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany

    Hermann Brenner

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  1. Haifa Maalmi
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Correspondence to Hermann Brenner.

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Maalmi, H., Walter, V., Jansen, L. et al. Relationship of very low serum 25-hydroxyvitamin D3 levels with long-term survival in a large cohort of colorectal cancer patients from Germany. Eur J Epidemiol 32, 961–971 (2017). https://doi.org/10.1007/s10654-017-0298-z

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  • DOI: https://doi.org/10.1007/s10654-017-0298-z

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