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.