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Effect of Vitamin D Receptor Polymorphisms on Plasma Oxidative Stress and Apoptotic Biomarkers Among Breast Cancer Survivors Supplemented Vitamin D3 Publisher Pubmed



Kazemian E1, 2 ; Akbari ME3 ; Moradi N4, 5 ; Gharibzadeh S6 ; Amouzegar A2 ; Jamshidinaeini Y7 ; Mondul AM8 ; Khademolmele M9 ; Ghodoosi N10 ; Zarins KR11 ; Shateri Z9 ; Davoodi SH1, 3 ; Rozek LS11
Authors
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Authors Affiliations
  1. 1. Department of Basic Sciences and Cellular and Molecular Nutrition, Fac. of Nutr. Sci. and Food Technology and National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Iran
  2. 2. Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Iran
  3. 3. Cancer Research Center, Shahid Beheshti University of Medical Sciences, National Nutrition and Food Technology Research Institute, Faculty of Nutrition Sciences and Food Technology, No 7, west Arghavan st. Farahzadi Blv, Shahrake Gharb, Tehran, 1981619573, Iran
  4. 4. Department of Clinical Biochemistry, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
  5. 5. Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Iran
  6. 6. Department of Epidemiology and Biostatistics, Pasteur Institute of Iran, Tehran, Iran
  7. 7. Department of Nutritional Sciences, Texas Tech University, Lubbock, TX, United States
  8. 8. Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, United States
  9. 9. Department of Nutrition Science, Faculty of Medical Science and Technology, Islamic Azad University, Science and Research Branch (SRBIAU), Iran
  10. 10. Department of Community Nutrition, School of Nutritional Sciences and Dietetic, Tehran University of Medical Sciences, Tehran, Iran
  11. 11. Department of Environmental Health Sciences, University of Michigan, Ann Arbor, MI, United States

Source: European Journal of Cancer Prevention Published:2020


Abstract

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.
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