RT Journal Article SR Electronic T1 Effects of Supplemental Calcium and Vitamin D on Expression of Toll-Like Receptors and Phospho-IKKα/β in the Normal Rectal Mucosa of Colorectal Adenoma Patients JF Cancer Prevention Research JO Cancer Prev Res (Phila) FD American Association for Cancer Research SP 707 OP 716 DO 10.1158/1940-6207.CAPR-18-0123 VO 11 IS 11 A1 Hodge, Rebecca A1 Mandle, Hannah B. A1 Ray, Stephen A1 Tandon, Sonia A1 Peterson, Meaghan A1 Henry, Abigail A1 Jahan, Ferdous A. A1 Bostick, Roberd M. A1 Baron, John A. A1 Barry, Elizabeth L. A1 Yacoub, Rami A1 Rutherford, Robin E. A1 Seabrook, March E. A1 Fedirko, Veronika YR 2018 UL http://cancerpreventionresearch.aacrjournals.org/content/11/11/707.abstract AB Chronic inflammation in the colorectum, a significant contributor to colorectal carcinogenesis, can be triggered by the activation of proinflammatory signaling pathways such as those initiated by Toll-like receptors (TLR) and nuclear factor κB (NF-κB). Although experimental evidence supports calcium and vitamin D potentially modifying these proinflammatory pathways in the colorectum, human data in these regards are scarce. We investigated supplemental calcium (1,200 mg daily) and/or vitamin D3 (1,000 IU daily) effects on inflammatory signaling pathway-related biomarkers in a subset of 105 participants from a colorectal adenoma recurrence chemoprevention clinical trial. We assessed expression of TLR4 and TLR5, which recognize the bacterial components lipopolysaccharides and flagellin, respectively, and phospho-IKKα/β (pIKKα/β), a biomarker of inflammation, in the normal-appearing rectal crypt epithelium and stroma using standardized, automated immunohistochemistry and quantitative image analysis. Following 1 year of treatment, TLR4, TLR5, and pIKKα/β expression in the rectal mucosa did not statistically significantly change with vitamin D or calcium supplementation, taken alone or in combination. Several baseline participant characteristics, including body mass index, history of sessile serrated adenomas, high red/processed meat intake, and high levels of rectal epithelial cell proliferation (as measured by MIB-1/Ki-67), were associated with higher baseline expression of TLRs or pIKKα/β. Our findings suggest that vitamin D and calcium may have no substantial effect on the investigated biomarkers. However, several modifiable lifestyle factors may be associated with TLRs and pIKKα/β expression in the normal rectal mucosa, supporting their future investigation as potentially treatable, preneoplastic risk factors for colorectal neoplasms. Cancer Prev Res; 11(11); 707–16. ©2018 AACR.