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

Abstract

Objective Evidence suggests protective effects of vitamin D and anti-tumour 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+ 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 (Pheterogeneity=0.001); high 25(OH)D was associated with lower risk of tumour with high-level reaction [comparing the highest vs. lowest tertile: odds ratio, 0.10; 95% confidence interval, 0.03 to 0.35; Ptrend<0.001], but not risk of tumour with lower-level reaction (Ptrend>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 (Pheterogeneity=0.03; adjusted statistical significance level of α=0.006). Conclusion 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.

Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects

“…In a preclinical SMAD3 knockout model of colitis and colon cancer, Meeker et al (304) showed that a high vitamin D diet decreases NF-B activation in colonic epithelial cells, which is reflected by decreased inflammatory cell infiltrates and reduced expression of proinflammatory cytokines during initiation of carcinogenesis (304). In line with this, a strong inverse association is found between 25(OH)D status and the risk of colorectal cancer with high-level lymphocytic reactions which suggests a role for vitamin D in cancer immunoprevention through modulation of the host-tumor interaction (419). A recent whole genome profiling on cells derived from normal mammary tissue and breast cancer reveals the regulation of a set of immune genes by 1,25(OH) 2 D 3 .…”

658 Marine Omega-3 Polyunsaturated Fatty Acid Intake and Survival After Colorectal Cancer Diagnosis

“…Although moderately increased levels of ROS damage DNA and promote mutagenesis in cells, recent evidence indicates that high ROS levels exert an oxidative stress that can restrain tumor progression and metastasis by causing cell senescence or death. [27,28] Several lines of evidence also support a beneficial effect of marine ω-3 PUFAs on cancer survival. In a randomized controlled trial (RCT) of 60 patients, supplementation of marine ω-3 PUFAs restored the decreased ratio of T-helper cells to T-suppressor cells and prolonged the survival of cancer patients.…”

Vitamin D and Cancer Risk and Mortality: State of the Science, Gaps, and Challenges

“…There are, for example, important distinctions between such clinically relevant subgroups, including hormone receptor status in breast cancer, histological subtypes of non-Hodgkin lymphoma and ovarian, lung, and gastric cancers, and disease aggressiveness in prostate cancer. Interestingly, 1 recent study found that a higher vitamin D status was more beneficial for colorectal tumors having greater lymphocytic infiltration (138), supporting the view expressed in a recent commentary that substantially greater attention is needed with respect to organ site-specific biological mechanisms (139). The current literature also suggests that there may be other important factors that interact with vitamin D status, such as menopausal status in breast cancer (17), sex in colorectal cancer (140), and circulating vitamin D binding protein in prostate cancer (141).…”