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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

1
Department of Nutrition, Harvard School of Public Health, Boston, MA, United States.
2
Department of Epidemiology, Harvard School of Public Health, Boston, MA, United States.
3
Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, United States.
4
Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, United States.
5
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, United States.
6
Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States.
7
Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan.
8
Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, United States.
#
Contributed equally

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.

KEYWORDS:

COLORECTAL CANCER; EPIDEMIOLOGY; IMMUNOLOGY; IMMUNOTHERAPY; NUTRITION

PMID:
25591978
PMCID:
PMC4503524
DOI:
10.1136/gutjnl-2014-308852
[Indexed for MEDLINE]
Free PMC Article

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