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

Abstract

We investigated how vitamin D receptor (VDR) allelic variants affect breast cancer survivors’ responses to vitamin D3 supplementation to increase circulating 25-hydroxy vitamin D (25(OH)D) levels. Two hundred and fourteen patients who were diagnosed with breast cancer at least 6 mo, prior to the study and had completed all treatment regimens were assigned to consume 4000 IU of vitamin D3 daily for 12 weeks. Linear and multinomial logistic regression analyses were used to analyze the association of VDR single nucleotide polymorphism (SNPs) with changes in circulating 25(OH)D. The TaqI and BsmI VDR sequence variants modified the effect of vitamin D3 treatment on the plasma 25(OH)D changes (P value = 0.008 for TaqI and P value = 0.0005 for BsmI). Patients with the bb [Q4 vs. Q1 odds ratio(OR) 8.04, 95% confidence interval (CI) 1.55–41.57] and tt [Q4 vs. Q1 OR 4.64 95%CI 1.02–21.02] genotype of BsmI and TaqI had larger increases in plasma 25(OH)D levels compared to those with BB and TT genotype respectively after adjustment for potential confounders. Haplotype analyses suggested the existence of specific combination of alleles that might be associated with circulating 25(OH)D changes. VDR allelic variants modulate vitamin D3 supplementation to increase plasma 25(OH) levels in breast cancer survivors.

Acknowledgments

The research team would like to acknowledge the study participants whose contribution made the study possible.

Availability of Data and Materials

The datasets used during the current study are available from the corresponding author on reasonable request.

Competing Interests

The authors declare that they have no competing interests.

Ethics Approval and Consent to Participate

The protocol was approved by ethics committee of National Nutrition and Food Technology Research Institute (NNFTRI), Shahid Beheshti University of Medical Sciences (SBUM), Tehran, Iran (IR.SBMU.NNFTRI.REC.1395.62).

Authors' Contributions

Conceptualization, Elham Kazemian, Atieh Amouzegar and Sayed Hossein Davoodi; Data curation, Nariman Moradi, Maryam Khademolmele, Katie R Zarins and Nasim Ghodoosi; Formal analysis, Elham Kazemian, Safoora Gharibzadeh, Alison M Mondul and Laura S Rozek; Funding acquisition, Mohammad Esmaeil Akbari, Yasaman Jamshidi Naeini, Atieh Amouzegar and Sayed Hossein Davoodi; Investigation, Elham Kazemian, Nariman Moradi, Maryam Khademolmele and Nasim Ghodoosi; Methodology, Safoora Gharibzadeh, Alison M Mondul, Yasaman Jamshidi Naeini and Laura S Rozek; Project administration, Elham Kazemian, Atieh Amouzegar, Sayed Hossein Davoodi and Laura S Rozek; Resources, Mohammad Esmaeil Akbari; Software, Elham Kazemian and Katie R Zarins; Supervision, Atieh Amouzegar, Sayed Hossein Davoodi and Laura S Rozek; Visualization, Elham Kazemian; Writing – original draft, Elham Kazemian; Writing – review & editing, Mohammad Esmaeil Akbari, Nariman Moradi, Safoora Gharibzadeh, Alison M Mondul, Yasaman Jamshidi Naeini, Katie R Zarins, Atieh Amouzegar, Sayed Hossein Davoodi and Laura S Rozek.

Funding

This study was financially supported by Cancer Research Center, Shahid Beheshti University of Medical Sciences, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences.