Dietary fat, inflammation, circulating tumor cells, and circulating tumor DNA in colorectal cancer survivors: An exploratory cross-sectional study.

BACKGROUND: Inflammation contributes to cancer recurrence through signaling pathways responsible for cell growth and metastasis, impacting circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA). A high fat diet may contribute to inflammation directly or indirectly through changes in visceral adipose tissue (VAT), a body composition compartment associated with inflammation. OBJECTIVE: This analysis examined the association between percent energy from fat and circulating markers of inflammation, CTCs, and ctDNA. DESIGN: This study was an exploratory secondary analysis of cross-sectional data from the Exercise and Colorectal Cancer Treatment (EXACT) trial conducted from August 2019 to May 2023 at Pennington Biomedical Research Center. Estimated percent energy from fat was collected at baseline using the National Cancer Institute (NCI) Fat Screener. VAT was assessed using dual energy x-ray absorptiometry. PARTICIPANTS: /Setting: Participants included 57 stage I-III colorectal cancer survivors. MAIN OUTCOME MEASURES: Outcomes included eleven inflammatory biomarkers, CTCs, and ctDNA. STATISTICAL ANALYSES PERFORMED: Associations between percent energy from fat and inflammatory and tumor biomarkers was quantified using the Spearman correlation coefficient (r). Spearman partial correlations adjusted for age, sex, race, cancer stage, and moderate-to-vigorous physical activity (MVPA). Fully adjusted models additionally adjusted for VAT. RESULTS: In unadjusted analyses, percent energy from fat was associated with soluble interleukin (IL)-6 receptor (sIL-6r) (r = 0.32, 95% Confidence Interval (CI): 0.06-0.53), soluble tumor necrosis factor (TNF) receptor 1 (sTNFr1) (r = 0.32, 95% CI: 0.06-0.53), soluble TNF receptor 2 (sTNFr2) (r = 0.34, 95% CI: 0.09-0.55), and soluble IL-2 receptor alpha (sIL-2rα) (r = 0.29, 95% CI: 0.03-0.51). sTNFr2 remained associated with percent energy from fat in adjusted (r = 0.32, 95% CI: 0.06-0.55) and fully adjusted (r = 0.28, 95% CI: 0.02-0.51) models. CONCLUSIONS: This exploratory analysis provides insight into the mechanisms by which diet may impact cancer recurrence to support encouraging a healthy dietary pattern.