title: Vitamin D Reduces Colitis- and Inflammation-Associated Colorectal Cancer in Mice Independent of NOD2.
abstract: Inflammatory bowel disease (IBD) patients are at increased risk of developing colorectal cancer (CRC). Vitamin D (vD) induces NOD2 gene expression, enhancing immunity, while deficiency impairs intestinal epithelial integrity, increasing inflammation. This study investigated the effect of vD on CRC in colitis, and if preventive benefits are mediated via NOD2. Inflammation-associated CRC was induced by treating C57BL/6J and Nod2-/-mice with azoxymethane (AOM) and dextran sodium sulfate (DSS) cycles (×3). vD-deficient mice displayed more severe colitis compared to vD-supplemented mice, with greater weight loss, higher colitis activity index, increased colonic weight/length ratios, and lower survival rates. Increased histological inflammation score and increased IL-6 were observed in the mucosa of vD-deficient mice. Overall incidence of colonic tumors was not significantly different between vD-deficient and vD-supplemented mice. Higher tumor multiplicity was observed in vD-deficient vs vD-supplemented groups (both mouse strains). After AOM/DSS treatment, decreased plasma 25(OH)D3levels and downregulation of vD target genes Cyp24 and Vdr were observed in both mice strains (vD-deficient or vD-supplemented diet), compared to saline-treated controls on the vD-deficient diet. In conclusion, vD supplementation reduced colitis severity and decreased the number of inflammation-associated colorectal tumors in both C57BL/6J and Nod2-/-mice, independent of NOD2.
authors.affiliation: a Division of Gastroenterology, Faculty of Medicine, IBD Laboratory, Research Institute, McGill University Health Center, McGill University , Montreal , Quebec , Canada.
authors.forename: Ihsan
authors.initials: I
authors.lastname: Elimrani
authors.affiliation: a Division of Gastroenterology, Faculty of Medicine, IBD Laboratory, Research Institute, McGill University Health Center, McGill University , Montreal , Quebec , Canada.
authors.forename: Jamie
authors.initials: J
authors.lastname: Koenekoop
authors.affiliation: a Division of Gastroenterology, Faculty of Medicine, IBD Laboratory, Research Institute, McGill University Health Center, McGill University , Montreal , Quebec , Canada.
authors.forename: Serge
authors.initials: S
authors.lastname: Dionne
authors.affiliation: a Division of Gastroenterology, Faculty of Medicine, IBD Laboratory, Research Institute, McGill University Health Center, McGill University , Montreal , Quebec , Canada.|b Department of Nutrition and Biochemistry , Sainte Justine Hospital Research Center, University of Montreal , Montreal , Quebec , Canada.
authors.forename: Valerie
authors.initials: V
authors.lastname: Marcil
authors.affiliation: b Department of Nutrition and Biochemistry , Sainte Justine Hospital Research Center, University of Montreal , Montreal , Quebec , Canada.
authors.forename: Edgar
authors.initials: E
authors.lastname: Delvin
authors.affiliation: b Department of Nutrition and Biochemistry , Sainte Justine Hospital Research Center, University of Montreal , Montreal , Quebec , Canada.
authors.forename: Emile
authors.initials: E
authors.lastname: Levy
authors.affiliation: a Division of Gastroenterology, Faculty of Medicine, IBD Laboratory, Research Institute, McGill University Health Center, McGill University , Montreal , Quebec , Canada.
authors.forename: Ernest G
authors.initials: EG
authors.lastname: Seidman
mesh_terms: D000818:Animals; D001835:Body Weight; D002112:Calcifediol / Q000097:blood; D003092:Colitis / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D015179:Colorectal Neoplasms / Q000209:etiology / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D000072498:Cytochrome P450 Family 24 / Q000235:genetics; D016264:Dextran Sulfate / Q000633:toxicity; D005786:Gene Expression Regulation; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000235:genetics; D014807:Vitamin D / Q000494:pharmacology*
chemical_list: D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse; D018167:Receptors, Calcitriol; D014807:Vitamin D; D016264:Dextran Sulfate; D000072498:Cytochrome P450 Family 24; D002112:Calcifediol