Plasma 25-hydroxyvitamin D and colorectal cancer risk according to tumour immunity status

Gut. 2016 Feb;65(2):296-304. doi: 10.1136/gutjnl-2014-308852. Epub 2015 Jan 15.


Objective: Evidence suggests protective effects of vitamin D and antitumour immunity on colorectal cancer risk. Immune cells in tumour microenvironment can convert 25-hydroxyvitamin D [25(OH)D] to bioactive 1α,25-dihydroxyvitamin D3, which influences neoplastic and immune cells as an autocrine and paracrine factor. Thus, we hypothesised that the inverse association between vitamin D and colorectal cancer risk might be stronger for cancers with high-level immune response than those with low-level immune response.

Design: We designed a nested case-control study (318 rectal and colon carcinoma cases and 624 matched controls) within the Nurses' Health Study and Health Professionals Follow-up Study using molecular pathological epidemiology database. Multivariable conditional logistic regression was used to assess the association of plasma 25(OH)D with tumour subtypes according to the degree of lymphocytic reaction, tumour-infiltrating T cells (CD3+, CD8+, CD45RO+ (PTPRC) and FOXP3+ cells), microsatellite instability or CpG island methylator phenotype.

Results: The association of plasma 25(OH)D with colorectal carcinoma differed by the degree of intratumoural periglandular reaction (p for heterogeneity=0.001); high 25(OH)D was associated with lower risk of tumour with high-level reaction (comparing the highest versus lowest tertile: OR 0.10; 95% CI 0.03 to 0.35; p for trend<0.001), but not risk of tumour with lower-level reaction (p for trend>0.50). A statistically non-significant difference was observed for the associations of 25(OH)D with tumour subtypes according to CD3+ T cell density (p for heterogeneity=0.03; adjusted statistical significance level of α=0.006).

Conclusions: High plasma 25(OH)D level is associated with lower risk of colorectal cancer with intense immune reaction, supporting a role of vitamin D in cancer immunoprevention through tumour-host interaction.


Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • C-Reactive Protein / analysis
  • CD3 Complex / analysis
  • Case-Control Studies
  • Cell Count
  • Colorectal Neoplasms / immunology*
  • Colorectal Neoplasms / prevention & control
  • Databases as Topic
  • Female
  • Humans
  • Interleukin-6 / blood
  • Male
  • Middle Aged
  • Regression Analysis
  • T-Lymphocytes / cytology
  • Tumor Necrosis Factors / blood
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood


  • CD3 Complex
  • Interleukin-6
  • Tumor Necrosis Factors
  • Vitamin D
  • C-Reactive Protein
  • 25-hydroxyvitamin D