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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 Publisher Pubmed



Kazemian E1, 2 ; Akbari ME3 ; Moradi N4, 5 ; Gharibzadeh S6 ; Mondul AM7 ; Jamshidinaeini Y8 ; Khademolmele M9 ; Zarins KR10 ; Ghodoosi N11 ; Amouzegar A2 ; Davoodi SH1, 3 ; Rozek LS10
Authors
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Authors Affiliations
  1. 1. Department of Basic Sciences and Cellular and Molecular Nutrition, Faculty of Nutrition Sciences and Food Technology and National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, No 7, Hafezi St. Farahzadi Blv, Shahrake Gharb, Tehran, 19816-19573, Iran
  2. 2. Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, 19395-4763, Iran
  3. 3. Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, 19899–34148, Iran
  4. 4. Department of Clinical Biochemistry, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, 66177-13446, Iran
  5. 5. Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, 14496-14535, Iran
  6. 6. Department of Epidemiology and Biostatistics, Pasteur Institute of Iran, Tehran, 13169-43551, Iran
  7. 7. Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, 48109-2029, MI, United States
  8. 8. Department of Nutritional Sciences, Texas Tech University, Lubbock, 79409, TX, United States
  9. 9. Department of Nutrition Science, Faculty of Medical Science and Technology, Islamic Azad University, Science and Research Branch (SRBIAU), Tehran, 14778-93855, Iran
  10. 10. Department of Environmental Health Sciences, University of Michigan School of Public Health, M6529 SPH II, 1415 Washington Heights, Ann Arbor, 48109-2029, MI, United States
  11. 11. Department of Community Nutrition, School of Nutritional Sciences and Dietetic, Tehran University of Medical Sciences, Tehran, 14155-6446, Iran

Source: Nutrients Published:2019


Abstract

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. © 2019, MDPI AG. All rights reserved.
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