(LB04-07-25) Lipid Biomarkers of Habitual Alcohol Intake and Associations With Pancreatic Cancer Risk

Objectives: There is evidence supporting a modest positive association between alcohol intake and pancreatic ductal adenocarcinoma (PDAC) risk, however knowledge regarding mechanisms underlying the association is scarce. The objective of this study was to investigate the association between alcohol, lipidomic metabolites, and PDAC to provide mechanistic insights.

Methods: We measured 611 lipid species across 15 lipid classes in serum samples collected up to 24 years prior to PDAC diagnosis from two nested case-control studies (706 matched sets) within American and Finnish cohorts. We conducted cross-sectional analyses using multivariable-adjusted linear regressions to identify associations between self-reported alcohol intake and a 1-standard deviation increase in log-lipid concentrations among controls within each cohort. We then used multivariable conditional logistic regression and fixed-effects meta-analyses to calculate odds ratios (OR) for identified alcohol-associated lipids with PDAC risk across both cohorts.

Results: Alcohol intake was associated with 21 lipid species, 11 class-specific fatty acids (FA), 3 total FA, and 1 lipid class at Bonferroni significance thresholds with associations of similar direction in both cohorts. Among them, one total FA (FA(15:0)) and seven lipid species: triacylglycerols [TAG(49:3-FA18:2), TAG(51:3-FA18:2), TAG(49:2-FA18:2), TAG(51:3-FA15:0), TAG(51:2-FA18:2), TAG(51:2-FA15:0)] and a phosphatidylcholine (PC(15:0-18:2)) were inversely associated with PDAC at false discovery rate significance < 0.10, with ORs ranging from 0.82–0.86. There was no evidence of heterogeneity by smoking intensity.

Conclusions: Our findings from two prospective cohorts identified seven lipid species and one FA inversely associated with both alcohol intake and PDAC risk. These results suggest that alcohol intake may be positively associated with PDAC risk through down-regulation of circulating lipids years before PDAC diagnosis.

Funding Sources: This work was supported by the Intramural Research Program, Division of Cancer Epidemiology and Genetics of the United States National Cancer Institute, National Institutes of Health, Department of Health and Human Services.