Association of Vitamin D Receptor and Vitamin D-Binding Protein Polymorphisms with Familial Breast Cancer Prognosis in a Mono-Institutional Cohort.

Valentina Aristarco,Aliana Guerrieri-Gonzaga,Debora Macis,Davide Serrano,Gianluca Tolva,Harriet Johansson,Irene Feroce,Bernardo Bonanni,Sara Gandini,Chiara Accornero,Cristina Zanzottera

doi:10.3390/nu13041208

Valentina Aristarco, Aliana Guerrieri-Gonzaga + Show 9 more

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https://doi.org/10.3390/nu13041208

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Journal: Nutrients	Publication Date: Apr 6, 2021
Citations: 6	License type: CC BY 4.0

Affiliation: European Institute of Oncology

Abstract

Low 25-hydroxyvitamin D (25OHD) has been associated with an increased cancer incidence and poorer prognosis. Single nucleotide polymorphisms (SNPs) of vitamin D receptor (VDR) and vitamin D binding protein (GC gene) may interfere with vitamin D activity. This study assesses the role of VDR and GC SNPs on breast cancer (BC) recurrence and survival in a cohort of patients with a family history of breast cancer, without the pathogenic variant for BRCA1 and BRCA2. A consecutive series of patients who underwent genetic testing were genotyped for VDR and GC genes. Specifically, ApaI, FokI, TaqI, BsmI and rs2282679, rs4588, rs7041 SNPs were determined. A total of 368 wild type (WT) patients with BC were analyzed for VDR and GC SNPs. The GC rs2282679 minor allele was significantly associated with luminal subtype of the primary tumor compared to Her2+/TN breast cancer (p = 0.007). Multivariate Cox models showed that BmsI and TaqI are significantly associated with BC outcome. Patients with the major alleles showed more than 30% lower hazard of relapse (BsmI p = 0.02 and TaqI p = 0.03). Our study supports the evidence for a pivotal role of 25OHD metabolism in BC. GC SNPs may influence the hormone tumor responsiveness and VDR may affect tumor prognosis.

Highlights

There is a growing body of literature that links an individual’s vitamin D status with their health condition
Circulating 25OHD levels have been shown to be associated with tumor stage and survival, where lower levels were found in advanced stages of breast cancer and larger sized tumors, while higher levels were associated with a lower breast cancer risk in case-control studies [6,7], better prognosis in early breast cancer [8] and overall survival [9,10]
We aimed to investigate whether single nucleotide polymorphism (SNP) in the vitamin D receptor (VDR) and Globulin Complex (GC) gene may contribute to breast cancer relapse in patients with a family history of undefined origin

Summary

Introduction

There is a growing body of literature that links an individual’s vitamin D status with their health condition. The primary form of circulating vitamin D is 25 hydroxyvitamin. D (25OHD), and it is considered to be a robust indicator of vitamin D status. Circulating 25OHD levels have been shown to be associated with tumor stage and survival, where lower levels were found in advanced stages of breast cancer and larger sized tumors, while higher levels were associated with a lower breast cancer risk in case-control studies [6,7], better prognosis in early breast cancer [8] and overall survival [9,10].

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