ASPO Abstracts
CERAMIDES ARE ASSOCIATED WITH INCREASED CANCER RISK IN THE UTAH OBESITY COHORT STUDY
Category: Early Detection & Risk Prediction
Conference Year: 2022
Abstract Body:
Purpose: Excessive lipid deposition in non-adipose organs like the liver, pancreas or heart contributes to the development of cardiometabolic diseases like diabetes and heart failure. Ceramides are a particularly pathogenic lipid species, as they alter tissue metabolism such as inducing insulin resistance, a mechanism with demonstrated links to cancer risk as well. However, the relationship between circulating ceramides and cancer risk has rarely been evaluated. Methods: In the Utah Obesity Study, a large prospective cohort of gastric bypass (N= 418) and non-surgical patients with severe obesity (N=737), clinic-demographic factors and metabolic health parameters were measured at baseline, 2-years (post-weight loss in the surgery group), 6 and 12-years. We measured the association of a quantified panel of serum sphingolipids including ceramides as time-varying exposures with cancer incidence using pooled logistic regression analysis with Benjamini-Hochberg False Discovery Rate (FDR) correction for multiple testing, adjusting for age, sex, race, BMI, diabetes and smoking. Results: Participants were predominantly female (83%), white (97%), middle-aged (45±9 years), and morbidly obese (BMI 45.9±5 kg/m2; % fat 52±3%). After FDR correction, six ceramides were statistically significantly associated with cancer risk (ceramides: d18.1/16.0 (OR(95% CI) =4.62 (1.51, 14.72), d18.1/24.1 (OR(95% CI) =4.14 (1.47, 12.23); glucosylceramides: d18.1/16.0 (OR(95% CI) =5.57 (2.00, 16.06), d18.1/18.0 (OR(95% CI) =5.28 (1.71, 17.43), d18.1/24.0 (OR(95% CI) =4.51 (1.51, 14.12), d18.1/20.0(OR(95% CI) =4.64 (1.52, 15.24)). Conclusions: Multiple ceramide species were prospectively associated with cancer risk in the Utah Obesity Study. More studies in larger cohorts are needed to confirm these associations.
Keywords: ceramides, cancer