17 juli 2014: ik heb onderaan het abstract van de studie: Plasma Vitamin D Concentration Influences Survival Outcome After a Diagnosis of Colorectal Cancer, welke tegen betaling is in te zien toegevoegd.

Een omschrijving en de betekenis van deze studie staat hieronder.

19 maart 2014: Bron: European Journal of Cancer

Vitamine D zorgt voor significant minder risico op overlijden aan darmkanker. Het blijkt dat wanneer de 25-hydroxyvitamin D waarden in het bloed hoog (normaal) zijn deze ervoor kunnen zorgen dat patiënten met darmkanker een minder risico op overlijden aan alle oorzaken heeft (tot wel 29%) en zelfs tot 39% voor het risico op overlijden aan darmkanker specifiek in vergelijking met mensen met darmkanker waarvan hun 25-hydroxyvitamin D waarden in het bloed te laag zijn.

Dit blijkt uit een meta-analyse van 5 studies met totaal 2330 darmkankerpatienten. De resultaten van het effect van vitamine D bij borstkankerpatienten is in diezelfde 5 studies ook onderzocht met ook vergelijkbare resultaten en die studie staat hier onder borstkanker op kanker-actueel.

Volgens onderzoekers blijken 65% van de darmkankerpatiënten in de USA een vitamine D tekort te hebben. Bij borstkankerpatienten ligt dat lager maar is het vitamine D tekort nog altijd 39%.

Hoe de vitamine D precies werkt durf ik niet te vertalen in het Nederlands maar dit schrijven de onderzoekers van het Dana-Farber Cancer Institute erover:

The hypothesis that vitamin D status is related to colorectal cancer has received strong experimental support over the past two decades, based on the almost ubiquitous expression in colon cancer cells of the vitamin D receptor (VDR)8,9 and 1-a-hydroxylase (CYP27B1),10 which converts plasma 25-hydroxyvitamin D3 [25(OH)D] into 1,25-dihyroxycholecalciferol [1,25(OH)2D], the active metabolite. Binding of VDR by 1,25(OH)2D leads to transcriptional control of target genes, resulting in induction of differentiation and apoptosis,11,12 and inhibition of proliferation,13 angiogenesis,14,15 and metastatic potential.16,17

Hier een schematische weergave van 1 studie met 304 darmkankerpatiënten over de overlevingskansen gerelateerd aan de vitamine D bloedwaarden, waarbij een verschil van 48% in positieve zin op het effect van de behandeling van darmkanker bij 304 darmkankerpatiënten:

Figure. Plasma 25(OH)D and Survival in 304 Colorectal Cancer Patients (NHS/HPFS)

 Plasma 25(OH)D and Survival in 304 Colorectal Cancer
Patients (NHS/HPFS)

Adjusted for age, gender, stage, grade, site, year of diagnosis, season of blood draw, BMI, and post-diagnosis physical activity. (Ng K, et al. J Clin Oncol. 2008;26:2984-2991.)

Het volledige studierapport van de meta-analyse: Serum 25-hydroxyvitamin D levels and survival in colorectal and breast cancer patients: Systematic review and meta-analysis of prospective cohort studies is tegen betaling in te zien.

Hier het abstract van de studie met een referentielijst:    

Higher vitamin D serum levels (25 (OH) D) (>75nmol/L) were associated with significantly reduced mortality in patients with colorectal cancer

Eur J Cancer. 2014 Feb 27. pii: S0959-8049(14)00124-5. doi: 10.1016/j.ejca.2014.02.006. [Epub ahead of print]

Serum 25-hydroxyvitamin D levels and survival in colorectal and breast cancer patients: Systematic review and meta-analysis of prospective cohort studies.

Author information

  • 1German Cancer Research Center (DKFZ), Division of Clinical Epidemiology and Aging Research, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.
  • 2German Cancer Research Center (DKFZ), Division of Clinical Epidemiology and Aging Research, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany. Electronic address: h.brenner@dkfz.de.



To estimate the association between serum 25-hydroxyvitamin D (25(OH)D) levels and survival among colorectal and breast cancer patients.


We performed a comprehensive literature search of prospective cohort studies assessing the association of serum 25(OH)D levels with survival in colorectal and breast cancer patients. Study characteristics and results were extracted and dose-response relationships were graphically displayed in a standardised manner. Meta-analyses using random effects models were performed to estimate pooled hazard ratios.


The systematic search yielded five studies including 2330 colorectal cancer patients and five studies including 4413 breast cancer patients all of which compared mortality across two to five categories of 25(OH)D levels. Among colorectal cancer patients, pooled hazard ratios (95% confidence intervals) comparing highest with lowest categories were 0.71 (0.55-0.91) and 0.65 (0.49-0.86) for overall and disease-specific mortality, respectively. For breast cancer patients, the corresponding pooled estimates were 0.62 (0.49-0.78) and 0.58 (0.38-0.84), respectively. No significant evidence of heterogeneity between studies was observed.


Higher 25(OH)D levels (>75nmol/L) were associated with significantly reduced mortality in patients with colorectal and breast cancer. Randomised controlled trials are needed to evaluate whether vitamin D supplementation can improve survival in colorectal and breast cancer patients with low vitamin D status (25(OH)D<50nmol/L) at diagnosis and before treatment.

Copyright © 2014 Elsevier Ltd. All rights reserved.


  1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893–2917
  2. Gong J, Hutter C, Baron JA, et al. A pooled analysis of smoking and colorectal cancer: timing of exposure and interactions with environmental factors. Cancer Epidemiol Biomarkers Prev. 2012;21:1974–1985
  3. Terry PD, Rohan TE. Cigarette smoking and the risk of breast cancer in women: a review of the literature. Cancer Epidemiol Biomarkers Prev. 2002;11:953–971
  4. Giovannucci E. Diet, body weight, and colorectal cancer: a summary of the epidemiologic evidence. J Womens Health. 2003;12:173–182
  5. Wei EK, Wolin KY, Colditz GA. Time course of risk factors in cancer etiology and progression. J Clin Oncol. 2010;28:4052–4057
  6. Assi HA, Khoury KE, Dbouk H, Khalil LE, Mouhieddine TH, El Saghir NS. Epidemiology and prognosis of breast cancer in young women. J Thorac Dis. 2013;5:S2–S8
  7. Yin L, Ordóñez-Mena JM, Chen T, Schottker B, Arndt V, Brenner H. Circulating 25-hydroxyvitamin D serum concentration and total cancer incidence and mortality: a systematic review and meta-analysis. Prev Med. 2013;57:753–764
  8. Grant WB. Ecological studies of the UVB-vitamin D-cancer hypothesis. Anticancer Res. 2012;32:223–236
  9. Ma Y, Zhang P, Wang F, Yang J, Liu Z, Qin H. Association between vitamin D and risk of colorectal cancer: a systematic review of prospective studies. J Clin Oncol. 2011;29:3775–3782
  10. Wang D, Velez de-la-Paz OI, Zhai JX, Liu DW. Serum 25-hydroxyvitamin D and breast cancer risk: a meta-analysis of prospective studies. Tumour Biol. 2013;34:3509–3517
  11. Zerwekh JE. Blood biomarkers of vitamin D status. Am J Clin Nutr. 2008;87:1087S–1091S
  12. Grant WB. Update on evidence that support a role of solar ultraviolet-B irradiance in reducing cancer risk. Anticancer Agents Med Chem. 2013;13:140–146
  13. Mohr SB, Garland CF, Gorham ED, Grant WB, Garland FC. Relationship between low ultraviolet B irradiance and higher breast cancer risk in 107 countries. Breast J. 2008;14:255–260
  14. Chen P, Li M, Gu X, et al. Higher blood 25(OH)D level may reduce the breast cancer risk: evidence from a Chinese population based case-control study and meta-analysis of the observational studies. PLoS One. 2013;8:e49312
  15. Chiang KC, Chen TC. The anti-cancer actions of vitamin D. Anticancer Agents Med Chem. 2013;13:126–139
  16. Buttigliero C, Monagheddu C, Petroni P, et al. Prognostic role of vitamin D status and efficacy of vitamin D supplementation in cancer patients: a systematic review. Oncologist. 2011;16:1215–1227
  17. Stroup DF, Berlin JA, Morton SC, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA. 2000;283:2008–2012
  18. Greenland S, Longnecker MP. Methods for trend estimation from summarized dose-response data, with applications to meta-analysis. Am J Epidemiol. 1992;135:1301–1309
  19. Higgins JPT, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539–1558
  20. van Houwelingen HC, Arends LR, Stijnen T. Advanced methods in meta-analysis: multivariate approach and meta-regression. Stat Med. 2002;21:589–624
  21. Thornton A, Lee P. Publication bias in meta-analysis: its causes and consequences. J Clin Epidemiol. 2000;53:207–216
  22. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–634
  23. R Development Core Team. R: a language and environment for statistical computing. R Foundation for Statistical Computing 2012. Vienna, Austria. ISBN 3-900051-07-0. Available from: http://www.R-project.org/.
  24. Ng K, Meyerhardt JA, Wu K, et al. Circulating 25-hydroxyvitamin D levels and survival in patients with colorectal cancer. J Clin Oncol. 2008;26:2984–2991
  25. Mezawa H, Sugiura T, Watanabe M, et al. Serum vitamin D levels and survival of patients with colorectal cancer: post-hoc analysis of a prospective cohort study. BMC Cancer. 2010;10:347
  26. Ng K, Sargent DJ, Goldberg RM, et al. Vitamin D status in patients with stage IV colorectal cancer: findings from Intergroup trial N9741. J Clin Oncol. 2011;29:1599–1606
  27. Fedirko V, Riboli E, Tjonneland A, et al. Prediagnostic 25-hydroxyvitamin D, VDR and CASR polymorphisms, and survival in patients with colorectal cancer in western European populations. Cancer Epidemiol Biomarkers Prev. 2012;21:582–593
  28. Tretli S, Schwartz GG, Torjesen PA, Robsahm TE. Serum levels of 25-hydroxyvitamin D and survival in Norwegian patients with cancer of breast, colon, lung, and lymphoma: a population-based study. Cancer Causes Control. 2012;23:363–370
  29. Ng K, Wolpin BM, Meyerhardt JA, et al. Prospective study of predictors of vitamin D status and survival in patients with colorectal cancer. Br J Cancer. 2009;101:916–923
  30. Goodwin PJ, Ennis M, Pritchard KI, Koo J, Hood N. Prognostic effects of 25-hydroxyvitamin D levels in early breast cancer. J Clin Oncol. 2009;27:3757–3763
  31. Vrieling A, Hein R, Abbas S, Schneeweiss A, Flesch-Janys D, Chang-Claude J. Serum 25-hydroxyvitamin D and postmenopausal breast cancer survival: a prospective patient cohort study. Breast Cancer Res. 2011;13:R74
  32. Hatse S, Lambrechts D, Verstuyf A, et al. Vitamin D status at breast cancer diagnosis: correlation with tumor characteristics, disease outcome, and genetic determinants of vitamin D insufficiency. Carcinogenesis. 2012;33:1319–1326
  33. Villaseñor A, Ballard-Barbash R, Ambs A, et al. Associations of serum 25-hydroxyvitamin D with overall and breast cancer-specific mortality in a multiethnic cohort of breast cancer survivors. Cancer Causes Control. 2013;24:759–767
  34. Brenner H, Kloor M, Pox CP. Colorectal cancer. Lancet. 2013;[Published Online First]
  35. Yin L, Grandi N, Raum E, Haug U, Arndt V, Brenner H. Meta-analysis: longitudinal studies of serum vitamin D and colorectal cancer risk. Aliment Pharmacol Ther. 2009;30:113–125
  36. Rose AA, Elser C, Ennis M, Goodwin PJ. Blood levels of vitamin D and early stage breast cancer prognosis: a systematic review and meta-analysis. Breast Cancer Res Treat. 2013;141:331–339
  37. McCarthy K, Laban C, Bustin SA, et al. Expression of 25-hydroxyvitamin D-1-alpha-hydroxylase, and vitamin D receptor mRNA in normal and malignant breast tissue. Anticancer Res. 2009;29:155–157
  38. Ditsch N, Toth B, Mayr D, et al. The association between vitamin D receptor expression and prolonged overall survival in breast cancer. J Histochem Cytochem. 2012;60:121–129
  39. Ruggiero M, Pacini S, Aterini S, Fallai C, Ruggiero C, Pacini P. Vitamin D receptor gene polymorphism is associated with metastatic breast cancer. Oncol Res. 1998;10:43–46
  40. Gonzalez-Sancho JM, Larriba MJ, Ordonez-Moran P, Palmer HG, Munoz A. Effects of 1alpha,25-dihydroxyvitamin D3 in human colon cancer cells. Anticancer Res. 2006;26:2669–2681
  41. Autier P, Boniol M, Pizot C, Mullie P. Vitamin D status and ill health: a systematic review. Lancet Diab Endocrinol. 2014;2:76–89
  42. Muindi JR, Adjei AA, Wu ZR, et al. Serum vitamin D metabolites in colorectal cancer patients receiving cholecalciferol supplementation: correlation with polymorphisms in the vitamin D genes. Horm Cancer. 2013;4:242–250
  43. Yao S, Sucheston LE, Millen AE, et al. Pretreatment serum concentrations of 25-hydroxyvitamin D and breast cancer prognostic characteristics: a case-control and a case-series study. PLoS One. 2011;6:e17251
  44. Bjelakovic G, Gluud LL, Nikolova D, et al. Vitamin D supplementation for prevention of mortality in adults. Cochrane Database Syst Rev. 2014;1:CD007470
  45. Cescon DW, Ganz PA, Beddows S, Ennis M, Mills BK, Goodwin PJ. Feasibility of a randomized controlled trial of vitamin D vs. placebo in women with recently diagnosed breast cancer. Breast Cancer Res Treat. 2012;134:759–767
  46. Crew KD, Shane E, Cremers S, McMahon DJ, Irani D, Hershman DL. High prevalence of vitamin D deficiency despite supplementation in premenopausal women with breast cancer undergoing adjuvant chemotherapy. J Clin Oncol. 2009;27:2151–2156
  47. Vashi PG, Trukova K, Lammersfeld CA, Braun DP, Gupta D. Impact of oral vitamin D supplementation on serum 25-hydroxyvitamin D levels in oncology. Nutr J. 2010;9:60
  48. Gama R, Waldron JL, Ashby HL, et al. Hypovitaminosis D and disease: consequence rather than cause?. BMJ. 2012;345:e5706
  49. Fakih MG, Trump DL, Johnson CS, Tian L, Muindi J, Sunga AY. Chemotherapy is linked to severe vitamin D deficiency in patients with colorectal cancer. Int J Colorectal Dis. 2009;24:219–224

Plasma Vitamin D Concentration Influences Survival Outcome After a Diagnosis of Colorectal Cancer

©American Society of Clinical Oncology

JCO JCO.2013.54.5947

Plasma Vitamin D Concentration Influences Survival Outcome After a Diagnosis of Colorectal Cancer

  1. Malcolm G. Dunlop

+ Author Affiliations

  1. Lina Zgaga, Susan M. Farrington, Farhat V.N. Din, Li Yin Ooi, Dominik Glodzik, Albert Tenesa, Harry Campbell, and Malcolm G. Dunlop, University of Edinburgh and Western General Hospital; Evropi Theodoratou and Harry Campbell, University of Edinburgh, Edinburgh; Albert Tenesa, University of Edinburgh, Roslin; Susan Johnston, Glasgow Royal Infirmary, Glasgow, United Kingdom; Lina Zgaga, Trinity College Dublin, Dublin, Ireland.
  1. Corresponding author: Malcolm G. Dunlop, MD, Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, United Kingdom; e-mail: malcolm.dunlop@igmm.ed.ac.uk.
  1. L.Z. and E.T. contributed equally to this work.


Purpose We investigated whether the plasma level of 25-hydroxyvitamin D (25-OHD) after a diagnosis of colorectal cancer (CRC) influences survival outcome.

Patients and Methods We prospectively studied 1,598 patients with stage I to III CRC. We sought association between plasma 25-OHD and stage-specific survival and tested for interaction between 25-OHD level and variation at the vitamin D receptor (VDR) gene locus. Blood was sampled postoperatively, and plasma was assayed for 25-OHD by liquid chromatography-tandem mass spectrometry. VDR polymorphisms (rs1544410, rs10735810, rs7975232, rs11568820) were genotyped, and haplotypes were inferred by using BEAGLE software. We tested for association between survival and 25-OHD, VDR genotype/haplotype, and after applying a VDR genotype–25-OHD interaction term. We conducted Kaplan-Meier survival analysis and used Cox proportional hazards models to estimate adjusted hazard ratios (HRs).

Results We found strong associations between plasma 25-OHD concentration and CRC-specific (P = .008) and all-cause mortality (P = .003). Adjusted HRs were 0.68 (95% CI, 0.50 to 0.90) and 0.70 (95% CI, 0.55 to 0.89), respectively (highest v lowest 25-OHD tertile), particularly in stage II disease (HR, 0.44; P = .004 for CRC-specific mortality). We detected gene-environment interactions between 25-OHD concentration and rs11568820 genotype for CRC-specific (P = .008) and all-cause (P = .022) mortality, number of protective alleles (P = .004 and P = .018, respectively), and GAGC haplotype at the VDR locus for all-cause mortality (P = .008).

Conclusion In patients with stage I to III CRC, postoperative plasma vitamin D is associated with clinically important differences in survival outcome, higher levels being associated with better outcome. We observed interactions between 25-OHD level and VDR genotype, suggesting a causal relationship between vitamin D and survival. The influence of vitamin D supplementation on CRC outcome will require further investigation

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