Abstract
Pancreatic ductal carcinoma (PDAC) is highly fatal with limited understanding of mechanisms underlying its carcinogenesis. We comprehensively investigated whether lipidomic measures were associated with PDAC in two prospective studies. We measured 904 lipid species and 252 fatty acids across 15 lipid classes in pre-diagnostic serum (up to 24 years) in a PDAC nested-case control study within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO, NCT00002540) with 332 matched case–control sets including 272 having serial blood samples and Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC, NCT00342992) with 374 matched case–control sets. Controls were matched to cases by cohort, age, sex, race, and date at blood draw. We used conditional logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI) per one-standard deviation increase in log-lipid concentrations within each cohort, and combined ORs using fixed-effects meta-analyses. Forty-three lipid species were associated with PDAC (false discovery rate, FDR ≤ 0.10), including lysophosphatidylcholines (LPC, n = 2), phosphatidylethanolamines (PE, n = 17), triacylglycerols (n = 13), phosphatidylcholines (PC, n = 3), diacylglycerols (n = 4), monoacylglycerols (MAG, n = 2), cholesteryl esters (CE, n = 1), and sphingomyelins (n = 1). LPC(18:2) and PE(O-16:0/18:2) showed significant inverse associations with PDAC at the Bonferroni threshold (P value < 5.5 × 10–5). The fatty acids LPC[18:2], LPC[16:0], PC[15:0], MAG[18:1] and CE[22:0] were significantly associated with PDAC (FDR < 0.10). Similar associations were observed in both cohorts. There was no significant association for the differences between PLCO serial lipidomic measures or heterogeneity by follow-up time overall. Results support that the pre-diagnostic serum lipidome, including 43 lipid species from 8 lipid classes and 5 fatty acids, is associated with PDAC.
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Abbreviations
- ATBC:
-
Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study
- AUC:
-
Area under the curve
- BMI:
-
Body mass index
- CE:
-
Cholesteryl ester
- CI:
-
Confidence interval
- DAG:
-
Diacylglycerol
- DCER:
-
Dihydroceramide
- LASSO:
-
Least absolute shrinkage and selection operator
- LPC:
-
Lysophosphatidylcholine
- MAG:
-
Monoacylglycerol
- OR:
-
Odds ratio
- PDAC:
-
Pancreatic ductal adenocarcinoma
- PE:
-
Phosphatidylethanolamine
- PLCO:
-
Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial
- SM:
-
Sphingomyelin
- TAG:
-
Triacylglycerol
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Acknowledgements
We thank all the participants, the investigators, and support staff of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening cohort study without whom this research would not be possible.
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Division of Cancer Epidemiology and Genetics intramural research program (National Cancer Institute, National Institute of Health, Bethesda, Maryland, United States of America).
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All authors have directly participated in the different steps of the study and are responsible for its content. RSS was involved in the conceptualization, funding acquisition, resources mobilization, project administration, and supervision of the study. RSS, SW, NF and DA were involved in data curation. SN, JS, SM and RSS were responsible for leading the investigation. JS and RSS provided methodological expertise. SN and JS developed the software programs and were responsible of the formal analysis. SN, SM, RSS were involved in the visualization of the findings. SN was responsible for writing of the original draft. SN, JS, SM, RSS, SW, NF, DA were involved in writing, reviewing, and editing the manuscript.
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Naudin, S., Sampson, J.N., Moore, S.C. et al. Lipidomics and pancreatic cancer risk in two prospective studies. Eur J Epidemiol 38, 783–793 (2023). https://doi.org/10.1007/s10654-023-01014-3
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DOI: https://doi.org/10.1007/s10654-023-01014-3