Abstract

Abstract Background: Vitamin D regulates estrogen synthesis among other mechanisms involved in breast cancer (BC) carcinogenesis. An important gap, to our knowledge, is whether blood levels of vitamin D are associated with DNA repair capacity in women with BC. Previously, we reported that a low DNA repair capacity (DRC) is a risk factor for BC and that DRC levels are associated with estrogen receptor (ER) positivity in women with BC. Moreover, we also reported that there is an intrinsic variability in DRC levels among the four principal BC subtypes. Therefore, our aim is to study the link between DRC and plasma vitamin D levels in BC and among BC subtypes. Methods: Treatment-naïve BC cases and controls were selected from our cohort of Hispanic women (n=1,187). DRC was assessed in lymphocytes through the host-cell reactivation assay. Vitamin D was measured using LC/MS/MS. Results: Women with BC (n=91) had higher (+6.6 ng/ml) vitamin D than controls (n=22) (p=0.007). There were significant differences in vitamin D levels (p<0.05) between BC cases with high (≥3.8%) (n=17) and low (<3.8%) (n=74) DRC levels. Vitamin D and DRC were negatively correlated in BC cases (r=-0.2296, p=0.03). When women with BC and low DRC levels (n=56) were stratified into: luminal A (n=17), luminal B (n=11), HER2+ (n=10), and triple-negative (n=18), women with HER2+ and TNBC showed the highest levels of vitamin D (p<0.05). Women with ER- had higher levels (+7.6 ng/ml) of vitamin D than women with ER+ tumors (p=0.005). After finding that plasma vitamin D levels from women with BC and controls were significantly different when stratified by DRC levels and BC subtypes, ROC curves were constructed to examine whether these levels could allow us to discriminate between our four study groups. Significant differences (p=0.0126) were found for cases and controls with low DRC; AUC of 0.7178. When considering all women with BC independently of DRC levels, the AUC was 0.7353 (p=0.0300). Conclusions: This study provides the first evidence of a link between vitamin D and DRC levels in women with BC. We also present data as to how vitamin D varies across four molecular subtypes of BC in Hispanic women. Impact: Our results fills an important gap on the link between plasma vitamin D and DRC levels in women with BC. Funding: This study was supported by grants #S06GM008239-20, 9SC1CA182846-04, and 5SC1CA157250-02, 5U54CA163071-04, 5R25GM096955-08. Citation Format: Carmen Ortiz, Jarline Encarnacion, Ralphdy Vergne, Luis Padilla, Jaime Matta. Plasma vitamin D levels and DNA repair capacity in four molecular subtypes of women with breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1760.

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