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. 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

Mingyang Song #  1   2 , Reiko Nishihara #  1   3 , Molin Wang #  2 , Andrew T Chan #  4   5 , Zhi Rong Qian  3 , Kentaro Inamura  3   6 , Xuehong Zhang  5 , Kimmie Ng  3 , Sun A Kim  3 , Kosuke Mima  3 , Yasutaka Sukawa  3 , Katsuhiko Nosho  7 , Charles S Fuchs #  3   5 , Edward L Giovannucci #  1   2   5 , Kana Wu #  1 , Shuji Ogino #  2   3   5   8
Affiliations

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

Mingyang Song et al. Gut. 2016 Feb.

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.

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Figures

Figure 1
Figure 1
Flow diagram of the nested case-control study design within the Nurses’ Health Study (NHS) and the Health Professionals Follow-up Study (HPFS).
See this image and copyright information in PMC

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