Abstract 167: A comparison of 25-OH-vitamin D levels and VDR polymorphisms in healthy and patients with breast intraepithelial neoplasia or cancer .
Authors: Davide Serrano, Harriet Johansson, Debora Macis, Ernst Lien, Jennifer Gjerde, Antonella Puccio, Sara Gandini, Aliana Guerrieri-Gonzaga, Irene Feroce, Matteo Lazzeroni, Andrea Decensi, Bernardo Bonanni
Journal: Cancer Research (2013)

Abstract Background: Vitamin D is mainly synthesized in the skin through UVB irradiation, while a minor intake comes from the diet. Vitamin D is converted in the liver to 25-hydroxyvitamin D-(25(OH)D) and circulating levels of this metabolite is an appropriate index of vitamin D status. A further hydroxylation occurs to produce the biologically active metabolite 1,25-dihydroxyvitamin D. Epidemiological studies have suggested a role for vitamin D in cancer prevention showing an inverse relationship between incidence of cancers and mortality and 25(OH)D plasma levels. Vitamin D exerts its activity through a nuclear receptor (VDR) that regulates the expression of multiple genes, including genes for cell cycle regulation, differentiation, and apoptosis Methods: We have collected plasma from pre and post menopausal healthy women (HW) and newly diagnosed patients with an intraepithelial neoplasia (IEN) or breast carcinoma (BC). We measured circulating levels of 25(OH)D3 using LC-MS/MS. The median values were then correlated with the disease status. In a subgroup, we performed a correlation with VDR polymorphisms (SNPs) and disease recurrences. BsmI, FokI, TaqI and ApaI SNPs were determined using the Applied Biosystems’ Taqman Allelic Discrimination Assay. Results: 25(OH)D3 was measured in 249 HW, 175 subjects with IEN and 168 BC patients undergoing surgery. Age and BMI were taken into account for adjustments the median age being 51, 46 and 59 years and median BMI being 24, 23 and 25.6 kg/m2 in the HW, IEN and BC categories, respectively. Median 25(OH)D3 were respectively: 37.2, (inter-quartile range, IQR 25.0-49.7) 43 (IQR 30.0-60.0) and 42 (IQR 30.0-60.0) nmol/L respectively. The LS means with BC + IEN combined versus HW were 43 (IQR 40.8-45.2) vs 46.4 (IQR 43.9-49.0) nmol/L. The levels of 25(OH)D3 are statistical different between healthy versus affected subjects (p = 0.05). We also conducted an exploratory analysis in a subgroup of 228 subjects to evaluate the correlation of VDR polymorphisms and the disease free survival (DFS for breast recurrence or new event). With a follow-up of 160 months and a total of 70 breast events, the homozygote and heterozygote subjects for VDR ApaI polymorphism had a worst DFS compared to the wild type ones (log rank test p= 0.04).Conclusions: our data confirm the possible role of the vitamin D and its receptor in the carcinogenesis process. It is not clear when 25(OH)D level starts to decline and thus may influence the disease progression. In accordance with other research groups the ApaI polymorphism may have, together with other VDR SNPs, an influence on BC incidence and recurrence. Further correlations and analysis of the VDR genotype are ongoing. A prospective study to clarify is recommended the issue of the timing of 25(OH)D levels measurement is warranted. Citation Format: Davide Serrano, Harriet Johansson, Debora Macis, Ernst Lien, Jennifer Gjerde, Antonella Puccio, Sara Gandini, Aliana Guerrieri-Gonzaga, Irene Feroce, Matteo Lazzeroni, Andrea Decensi, Bernardo Bonanni. A comparison of 25-OH-vitamin D levels and VDR polymorphisms in healthy and patients with breast intraepithelial neoplasia or cancer . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 167. doi:10.1158/1538-7445.AM2013-167