Vitamin D Receptor Genetic Variation and Cancer Biomarkers among Breast Cancer Patients Supplemented with Vitamin D3: A Single-Arm Non-Randomized Before and After Trial

We investigated whether vitamin D receptor (VDR) polymorphisms were associated with cancer biomarkers, i.e., E-cadherin, matrix metallopeptidase 9 (MMP9), interferon β (IFNβ), soluble intercellular adhesion molecule-1 (s-ICAM-1), soluble vascular cell adhesion molecule-1 (s-VCAM-1), tumor necrosis factorα (TNFα), interleukin 6 (IL6), plasminogen activator inhibitor-1(PAI-1), and human high sensitivity C-reactive protein (hs-CRP), among breast cancer survivors who received vitamin D3 supplementation. In a single-arm non-randomized pre- and post trial, 176 breast cancer survivors who had completed treatment protocol including surgery, radio and chemotherapy were enrolled in the study and received 4000 IU of vitamin D3 daily for 12 weeks. The association between the VDR SNPs (ApaI, TaqI, FokI, BsmI and Cdx2) and response variable changes was assessed using linear regression, utilizing the "association" function in the R package "SNPassoc". We observed that women with AA and GA codominant model (AA compared to GG) and (GA compared to GG); dominant model (AA & GA compared to GG) genotypes of Cdx2 showed higher increase in plasma MMP9 levels compared to the GG category. In addition, carriers of BsmI bb showed greater decrease in circulating TNFα levels after vitamin D3 supplementation recessive model (bb compared to BB & Bb. Likewise, significant associations were identified between haplotypes of VDR polymorphisms and on-study plasma MMP9 changes. However, our results indicate that VDR genetic polymorphisms were not associated with longitudinal changes in the remaining cancer biomarkers. Overall, our findings suggest that changes in certain inflammatory biomarkers in breast cancer survivors with low plasma 25(OH)D levels, supplemented with vitamin D3, may depend on VDR SNPs and haplotypes

Effect of vitamin D receptor polymorphisms on plasma oxidative stress and apoptotic biomarkers among breast cancer survivors supplemented vitamin D3

We investigated whether plasma oxidative stress and apoptotic biomarkers were associated with the VDR polymorphisms in breast cancer survivors supplemented with vitamin D3. Two hundred fourteen breast cancer survivors received 4000 IU of vitamin D3 daily for 12 weeks. Linear regression was used to analyze whether the effect of vitamin D3 supplementation on response variables was associated with the selected VDR single nucleotide polymorphisms executing by 'association' function in the R package 'SNPassoc'. Linear regression analyses adjusted for age, BMI and on-study plasma 25(OH)D changes indicated that the aa genotype of the ApaI codominant model (aa vs. AA):-0.21 (-0.39 to-0.03); recessive model (aa vs. AA and Aa):-0.20 (-0.37 to-0.03) and bb genotypes of the BsmI recessive model (bb vs. BB and Bb):-0.20 (-0.39 to-0.01) on VDR were associated with greater decrease in plasma Bcl2. Our findings indicated that, the Ff genotype of FokI was accompanied by higher increase in plasma MDA levels codominant model (Ff vs. FF): 0.64 (0.18-1.11); dominant model (ff and Ff vs. FF): 0.52 (0.09-0.05). This observed association was not remained statistically significant after correction for multiple testing. Haplotype score analyses revealed statistically significant association between the FokI BsmI ApaI haplotype and circulating MDA changes (P-value for global score = 0.001) after false-discovery rate correction. Our study suggests that genetic variations in the VDR do not powerfully modify the effects of vitamin D3 intake on biomarkers associated with antioxidant activity, oxidative stress and apoptosis in breast cancer survivors. © 2020 Lippincott Williams and Wilkins. All rights reserved