Abstract 4870: High dietary vitamin D prevents dysplastic lesions in an AOM/DSS model of colorectal cancer.

Abstract

Abstract Diet and lifestyle have an important impact on the etiology of colorectal cancer (CRC), one of the leading causes of cancer morbidity and mortality in Western countries. Epidemiological studies suggest that vitamin D might have chemopreventive effects. In this study we investigated the effect of increasing dietary vitamin D3 intake on chemically induced colorectal tumor development in mice. We fed female C57BL/6J mice with a diet containing five different vitamin D3 concentrations ranging from 100 to 5000 IU/kg diet and studied the impact of dietary vitamin D3 on the development of chemically induced colonic dysplasia, a precursor of CRC. To induce dysplasia, we injected mice once with 10 mg/kg azoxymethane (AOM) intraperitoneally, followed by three cycles of dextran sodium sulfate salt (DSS) in the drinking water. Dietary vitamin D3 concentration correlated positively with 25(OH)D3 serum levels (Spearman Correlation Coefficient (SCC) 0.752, p<0.001). Both dietary vitamin D3 concentration and serum 25-hydroxyvitamin D3 levels correlated inversely with the dysplasia score (SCC -0.579, p=0.002; SCC -0.618, p=0.001). Dysplastic regions expressed less vitamin D receptor while the proliferation marker Ki67 was significantly higher expressed in regions with high grade dysplasia compared with the respective normal mucosa of the same colon. Our data show that high dietary vitamin D3 concentrations reduce the development of chemically induced precursors of colorectal cancer in mice. Citation Format: Doris M. Hummel, Julia Höbaus, Ursula Thiem, Joao Graca, Ildiko Mesteri, Lukas Gober, Barbara Obermayer-Pietsch, Enikö Kallay. High dietary vitamin D prevents dysplastic lesions in an AOM/DSS model of colorectal 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 4870. doi:10.1158/1538-7445.AM2013-4870