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

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

Author information

  • 1Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.
  • 2Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.
  • 3Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.
  • 4Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA.
  • 5Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.
  • 6Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
  • 7Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA.
  • 8Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan.
  • 9Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA.
  • 10Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA.
  • 11Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA.
  • 12Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA.

Abstract

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.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

KEYWORDS:

COLORECTAL CANCER; EPIDEMIOLOGY; IMMUNOLOGY; IMMUNOTHERAPY; NUTRITION

PMID:
25591978
[PubMed - indexed for MEDLINE]
PMCID:
PMC4503524
[Available on 2016-08-01]

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