Assi, Nada and Thomas, Duncan C. and Leitzmann, Michael and Stepien, Magdalena and Chajes, Veronique and Philip, Thierry and Vineis, Paolo and Bamia, Christina and Boutron-Ruault, Marie-Christine and Sandanger, Torkjel M. and Molinuevo, Amaia and Boshuizen, Hendriek C. and Sundkvist, Anneli and Kuehn, Tilman and Travis, Ruth C. and Overvad, Kim and Riboli, Elio and Gunter, Marc J. and Scalbert, Augustin and Jenab, Mazda and Ferrari, Pietro and Viallon, Vivian (2018) Are Metabolic Signatures Mediating the Relationship between Lifestyle Factors and Hepatocellular Carcinoma Risk? Results from a Nested Case-Control Study in EPIC. CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, 27 (5). pp. 531-540. ISSN 1055-9965, 1538-7755
Full text not available from this repository. (Request a copy)Abstract
Background: The "meeting-in-the-middle" (Nirmt) is a principle to identify exposure biornarkers that are also predictors of disease. The MITM statistical framework was applied in a nested case-control study of hepatocellular carcinoma (HCC) within European Prospective Investigation into Cancer and Nutrition (EPIC), where healthy lifestyle index (I-ILO variables were related to targeted serum metabolites. Methods: Lifestyle and targeted metabolomic data were available from 147 incident 11CC cases and 147 matched controls. Partial least squares analysis related 7 lifestyle variables from a modified HU to a set of 132 serum-measured metabolites and a liver function score. Mediation analysis evaluated whether metabolic profiles mediated the relationship between each lifestyle exposure and HCC risk. Results: Exposure-related metabolic signatures were identified, Particularly, the body mass index (BMI)-associated metabolic component was positively related to 0-mantic acid, tyrosine, PC aaC38:3, and liver function score and negatively to lysoPC aC17:0 and aC18:2. The lifetime alcohol-specific signature had negative loadings on sphingomyelins (SM C16:1, C18:1, SM(OH) C14:1, C16:1 and C22:2). Both exposures were associated with increased HCC with total effects (TE) = 1,23 (95% confidence interval = 0.93-1.62) and 1.40 (1.14-1.72), respectively, for 13MI and alcohol consumption. Both metabolic signatures mediated the association between BMI and lifetime alcohol consumption and HC-C-with natural indirect effects, respectively, equal to 1.56 (1.24-1,96) and 1.09 (1.03-1.15), accounting for a proportion mediated of 100 /0 and 24%. Conclusions: In a refined M ITM framework, relevant metabolic signatures were identified as mediators in the relationship between lifestyle exposures and HCC risk. Impact: The understanding of the biological basis for the relationship between modifiable exposures and cancer would pave avenues for clinical and public health interventions on metabolic mediators. Cancer Epiderniol Biomarkers Prey; 27(5); 531-40.(C) 2018 AACR.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SERUM METABOLITES; AMINO-ACID; CANCER; ALCOHOL; EPIDEMIOLOGY; BIOMARKERS; OBESITY; POPULATION; PLASMA; PHOSPHATIDYLCHOLINE; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Institut für Epidemiologie und Präventivmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 09 Mar 2020 14:07 |
| Last Modified: | 09 Mar 2020 14:07 |
| URI: | https://pred.uni-regensburg.de/id/eprint/14606 |
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