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.

Download Full-text

Vitamin D Receptor (VDR) Allelic Variants Correlating with Response to Vitamin D3 Supplementation in Breast Cancer Survivors

Nutrition and Cancer ◽

10.1080/01635581.2020.1869790 ◽

2021 ◽

pp. 1-14

Author(s):

Elham Kazemian ◽

Sayed Hossein Davoodi ◽

Mohammad Esmaeil Akbari ◽

Nariman Moradi ◽

Safoora Gharibzadeh ◽

...

Keyword(s):

Breast Cancer ◽

Vitamin D ◽

Cancer Survivors ◽

Vitamin D Receptor ◽

Vitamin D3 ◽

Breast Cancer Survivors ◽

Allelic Variants ◽

Vitamin D3 Supplementation

Download Full-text

Interaction Effects of Vitamin D Receptor Polymorphisms and Vitamin D3 Supplementation on Plasma Oxidative Stress and Apoptotic Biomarkers Among Breast Cancer Survivors (P05-027-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz030.p05-027-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Elham Kazemin ◽

Yasaman Jamshidi-naeini ◽

Mohammad Esmaeil Akbari ◽

Nariman Moradi ◽

Safoora Gharibzadeh ◽

...

Keyword(s):

Breast Cancer ◽

Oxidative Stress ◽

Vitamin D ◽

Linear Regression ◽

Cancer Survivors ◽

Vitamin D Receptor ◽

Vitamin D3 ◽

Multiple Testing ◽

Breast Cancer Survivors ◽

Vitamin D3 Supplementation

Abstract Objectives Interactions of human genes and environmental exposures play a crucial role in cancer etiology and prognosis. We investigated whether response to vitamin D3 supplementation in terms of plasma oxidative stress (OS) and apoptotic biomarkers were mediated by the vitamin D receptor (VDR) single-nucleotide polymorphisms (SNPs) among breast cancer survivors. Methods Two hundred and fourteen women who were diagnosed with breast cancer (invasive or in situ) and had completed all treatment regimens received 4000 IU of vitamin D3 daily for 12 weeks. Anthropometric, dietary, sun exposure, physical activity, as well as laboratory assessments including plasma superoxide dismutase (SOD), total antioxidant capacity (TAC), malondialdehyde (MDA), 8-hydroxy-2′-deoxyguanosine (8-OHdG), and Bcl2 were performed at enrolment and post-intervention. VDR genotyping was performed at ApaI, TaqI, FokI, BsmI, and Cdx-2. Linear regression was used to analyze whether the effect of vitamin D3 supplementation on response variables was modulated by the selected VDR SNPs. Results Linear regression analysis adjusted for age, BMI, on-study plasma 25(OH)D changes, and baseline circulating 25(OH)D indicated that the AA genotype of the ApaI on VDR was associated with greater increase and decrease in plasma Bcl2 [0.21, 95% Confidence Interval (CI) (0.03, 0.39)] and MDA [−0.68, 95% CI (−1.35, −0.02)] compared to aa respectively. This association did not remain statistically significant after correction for multiple testing. Overall, we found no statistically significant interaction of the VDR SNPs and inferred haplotypes with the circulating OS and apoptotic biomarkers except for the FokI BsmI ApaIhaplotype and circulating MDA (p-value for global score = 0.02) after multiple testing correction. Conclusions Our findings indicate a weak interaction between the VDR haplotypes and responses of plasma OS and apoptotic biomarkers to vitamin D3 supplementation. However, further assessments of additional genes and biomarkers with longer intervention periods may further explain the complex interplay between genes and nutrients. Funding Sources Cancer Research Center, National Nutrition and Food Technology Research Institute, and the Endocrine Research Center of Shahid Beheshti University of Medical Sciences.

Download Full-text