Abstract 3286: Correlation between vitamin D levels and DNA repair capacity in breast cancer patients stratified by molecular subtypes

Abstract

Vitamin D exists as vitamin D2 and D3, which are metabolized to 25-hydroxyvitamin D [25(OH)D], the major circulating vitamin D metabolite. Besides its physiological functions, vitamin D levels have also been studied as a risk factor for several hormonal cancers including breast cancer (BC). Worldwide, BC accounts for nearly a quarter of all cancers in women. Nutritional studies report that vitamin D intake is associated with a lower BC risk. Several discrepancies exist regarding the role of serum vitamin D in BC risk. While some studies report BC risk reduction by vitamin D only in premenopausal, others propose that it only occurs in postmenopausal women. BC tumors may (+) or may not (-) have three hormonal receptors: estrogen (ER), progesterone (PR), and HER2. Based on their status, four principal molecular BC subtypes have been identified: luminal A (ER+/−, PR+/−, HER2-), luminal B (ER+/−, PR+/−, HER2+), HER2+ (ER−, PR−, HER2+), and triple negative (TN) (ER−, PR−, HER2−). If BC is analyzed in terms of molecular subtypes, low vitamin D levels have been associated with aggressive phenotypes and worse prognosis. Vitamin D also influences estrogen synthesis. Since we have previously shown that a low DNA repair capacity (DRC), measured through the nucleotide excision repair pathway, is a risk factor for BC and vitamin D has also been found to affect DNA repair, the focus of this study is to examine the role of plasma vitamin D levels and DRC in BC. The main aim is to elucidate whether there is an association between vitamin D and DRC levels among the four molecular BC subtypes. We hypothesize that a negative correlation between 25(OH)D and DRC levels will be observed among these subtypes. As an initial effort, 47 BC cases and 20 controls without BC were selected from our large BC cohort. DRC was measured in lymphocytes of untreated women using the host cell reactivation assay. Pathology reports were examined to divide BC cases according to their molecular BC subtype: luminal A (n=13), luminal B (n=11), HER2+ (n=10), and TN (n=13). Plasma 25(OH)D levels were measured using the UniCel DxC System at a CLIA-certified lab. Our results show a negative correlation between 25(OH)D and DRC levels (p=0.04). Statistically significant differences were found for vitamin D levels among the different groups (p=0.0019, ANOVA). Moreover, higher 25(OH)D levels (47.97±2.4 ng/mL) were found in ER- BC cases (p=0.03, t-test). When comparing vitamin D levels in BC subtypes, a significant difference was found in HER2+ and TN groups when compared with the control group (p<0.05, Kruskal-Wallis). Based on these preliminary results we conclude that plasma vitamin D levels may be correlated with DRC levels in women with BC. Ongoing studies with a larger sample size are aimed at elucidating more precisely the potential association between vitamin D and DRC in these molecular BC subtypes. Citation Format: Carmen Ortiz, Jarline Encarnación, Ralphdy Vergne, Wanda Vargas, Jaime Matta. Correlation between vitamin D levels and DNA repair capacity in breast cancer patients stratified by molecular subtypes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3286. doi:10.1158/1538-7445.AM2017-3286