Abstract 755: Lipid metabolites and the risk of pancreatic cancer in two nested case-control studies
Authors: Sabine Naudin, Joshua N. Sampson, Steven C. Moore, Demetrius Albanes, Stephanie Weinstein, Rachael Stolzenberg-Solomon
Journal: Cancer Research (2021)

Abstract Background: Lipid metabolism pathways have been implicated in type 2 diabetes and inflammatory conditions and may be relevant to pancreatic ductal adenocarcinoma (PDA) etiology. Methods: We conducted an untargeted analysis of 903 lipid species metabolites within 15 lipid classes measured in pre-diagnostic serum (up to 24 years) to determine their association with incident PDA in a nested-case control study of 582 matched case-control sets from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC) and Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). Controls were matched to cases by age, sex, race, date of blood draw and follow-up time. We used conditional logistic regressions to calculate odd ratios (OR) and 95% confidence intervals (CI) per 1-standard deviation increase in the log-transformed and normalized lipid concentrations within each cohort and then combined ORs using a fixed-effect meta-analysis. Potential effect modification of the associations by overweight (BMI &amp;gt;25kg.m-2), diabetes status, smoking intensity and time until diagnosis (&amp;lt;5, 5-10, &amp;gt;10 years) was also evaluated. Results: Five lipid species from 4 different lipid classes were significantly associated with PDA risk at a false discovery rate (FDR) &amp;lt;0.05. Inverse associations were observed with 3 lipid species, including lysophosphatidylcholine LPC(18:2) (OR=0.78, 95%CI: 0.70-0.92), triacylglycerol TAG(49:3)- FA[18:2] (OR=0.81, 95%CI: 0.72-0.90) and plasmalogen phosphatidylethanolamine PE-O(16:0/18:2) (OR=0.81, 95%CI: 0.72-0.90), while positive associations were reported with 2 lipid species from the classes of phosphatidylethanolamines PE(16:0/18:1) (OR=1.24, 95%CI: 1.11-1.39) and monoacylglycerol MAG(18:1) (OR=1.25, 95%CI: 1.11-1.40). LPC(18:2) was significant after Bonferroni corrected level (P-value=2.37x10-5). Additional 10 lipid species, of which diacylglycerols (DAG(16:0/18:1)), monoacylglycerols (MAG(20:4)), triacylglycerols (TAG(51:3)-FA[18:2], TAG(51:2)-FA[18:0] and TAG(51:3)-FA[15:0]), cholesteryl esters (CE(22:0)), phosphatidylethanolamines (PE(16:0/20:4), PE(16:0/22:5) and PE(17:0/20:2)) and lysophosphatidylcholines (LPC(16:0)), were associated with PDA risk at a FDR &amp;lt;0.1. Similar associations were observed in ATBC and PLCO. Adjustment for diabetes, smoking habits and BMI did not alter the results. There was no evidence for heterogeneity by level of overweight, diabetes, smoking intensity and follow-up time. Conclusion: This untargeted lipidomics analysis showed evidence for associations between lipid metabolites from 6 different lipid classes and the risk of PDA. These findings support the role of prediagnostic lipid metabolites in PDA etiology. Citation Format: Sabine Naudin, Joshua N. Sampson, Steven C. Moore, Demetrius Albanes, Stephanie Weinstein, Rachael Stolzenberg-Solomon. Lipid metabolites and the risk of pancreatic cancer in two nested case-control studies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 755.