Abstract 1909: Associations of Vitamin D related polymorphisms with hereditary breast cancer in 1025 subjects undergoing BRCA 1/2 testing
Authors: Aristarco Valentina , Johansson Harriet , Macis Debora , Guerrieri Gonzaga Aliana , Gandini Sara , Serrano Davide , Feroce Irene , Barile Monica , Puccio Antonella , Brocca Lorenzo , Bonanni Bernardo 
Published: August 2015

Abstract
Background: Vitamin D plays an important role in many normal body functions, including regulation of cell growth, bone formation, inflammation, neuromuscular and immune function. Lower serum levels of 25-hydroxyvitamin D, an index of vitamin D status, are associated with greater risk of cancer. Genetic variants in vitamin D related genes have been linked to breast cancer (BC) risk. These include the vitamin D receptor (VDR) and the GC gene that encodes for the vitamin D binding protein.
Aims: To determinate the frequency of 5 single nucleotide polymorphisms (SNPs) of VDR and GC in a large cohort of subjects candidate to BRCA 1/2 genetic testing and to assess any interaction between vitamin D and BRCA pathways on disease outcome.
Methods: From 2002 to 2012 blood samples from 1025 subjects with family history of ovarian cancer (OC) or BC were collected after informed consent was signed during the genetic counseling. DNA was extracted from whole EDTA treated blood and Allelic Discrimination (Applied Biosystems’ Taqman assays) of VDR (BsmI, FokI, TaqI, ApaI) and GC SNPs is ongoing.
Results: At last follow-up in February 2014 our cohort included 272 unaffected subjects (117 BRCA carriers, 37 WT and 118 true negative) and 753 affected subjects (276 BRCA1/2 carriers, 469 WT and 1 true negative subjects). Amongst BC patients (N = 675), 221 were BRCA carriers, 446 WT, and 8 true negative. Those affected ofBC and OC (N = 27), included 23 BRCA carriers and 4 WT, while OC patients (N = 51) included 32 BRCA carriers and 19 WT. Here we present the preliminary data obtained for VDR and GC SNPs in 833 and 710 subjects, respectively. None of the genotypes deviated from the Hardy-Weinberg equilibrium. At the AACR meeting the genotyping of all subjects will be completed.
Conclusions: Our results of vitamin D genotyping will be correlated with BC tumor molecular subtype in affected subjects, and any association with BRCA mutation and outcome will be assessed. The study was funded by IEO Foundation and AVON.
Description of vitamin D genetic polymorphisms and their frequenciesSNPsType of polymorphismMinor Allele Frequency (MAF)MAF HapMapHWE Pvalue(1df chi-square test)rs 1544410; VDR BsmITransition C/TT: 0.420.440.50rs2228570; VDR FokITransition A/GA: 0.360.410.72rs731236; VDR TaqITransition A/GC: 0.410.440.52rs7975232; VDR ApaITransversion A/CG: 0.430.430.91rs22282679; GCTransversion G/TG: 0.280.260.52
Citation Format: Valentina Aristarco, Harriet Johansson, Debora Macis, Aliana Guerrieri Gonzaga, Sara Gandini, Davide Serrano, Irene Feroce, Monica Barile, Antonella Puccio, Lorenzo Brocca, Bernardo Bonanni. Associations of Vitamin D related polymorphisms with hereditary breast cancer in 1025 subjects undergoing BRCA 1/2 testing. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1909. doi:10.1158/1538-7445.AM2015-1909