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@article{Assi:2018:10.1158/1055-9965.EPI-17-0649,
author = {Assi, N and Thomas, DC and Leitzmann, M and Stepien, M and Chajès, V and Philip, T and Vineis, P and Bamia, C and Boutron-Ruault, M-C and Sandanger, TM and Molinuevo, A and Boshuizen, HC and Sundkvist, A and Kühn, T and Travis, RC and Overvad, K and Riboli, E and Gunter, MJ and Scalbert, A and Jenab, M and Ferrari, P and Viallon, V},
doi = {10.1158/1055-9965.EPI-17-0649},
journal = {Cancer Epidemiology, Biomarkers and Prevention},
pages = {531--540},
title = {Are metabolic signatures mediating the relationship between lifestyle factors and hepatocellular carcinoma risk? Results from a nested case-control study in EPIC},
url = {http://dx.doi.org/10.1158/1055-9965.EPI-17-0649},
volume = {27},
year = {2018}
}

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TY  - JOUR
AB  - Background: The "meeting-in-the-middle" (MITM) is a principle to identify exposure biomarkers 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 (HLI) variables were related to targeted serum metabolites.Methods: Lifestyle and targeted metabolomic data were available from 147 incident HCC cases and 147 matched controls. Partial least squares analysis related 7 lifestyle variables from a modified HLI 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 glutamic 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 BMI and alcohol consumption. Both metabolic signatures mediated the association between BMI and lifetime alcohol consumption and HCC 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% and 24%.Conclusions: In a refined MITM 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 medi
AU  - Assi,N
AU  - Thomas,DC
AU  - Leitzmann,M
AU  - Stepien,M
AU  - Chajès,V
AU  - Philip,T
AU  - Vineis,P
AU  - Bamia,C
AU  - Boutron-Ruault,M-C
AU  - Sandanger,TM
AU  - Molinuevo,A
AU  - Boshuizen,HC
AU  - Sundkvist,A
AU  - Kühn,T
AU  - Travis,RC
AU  - Overvad,K
AU  - Riboli,E
AU  - Gunter,MJ
AU  - Scalbert,A
AU  - Jenab,M
AU  - Ferrari,P
AU  - Viallon,V
DO  - 10.1158/1055-9965.EPI-17-0649
EP  - 540
PY  - 2018///
SN  - 1055-9965
SP  - 531
TI  - Are metabolic signatures mediating the relationship between lifestyle factors and hepatocellular carcinoma risk? Results from a nested case-control study in EPIC
T2  - Cancer Epidemiology, Biomarkers and Prevention
UR  - http://dx.doi.org/10.1158/1055-9965.EPI-17-0649
UR  - https://www.ncbi.nlm.nih.gov/pubmed/29563134
UR  - http://hdl.handle.net/10044/1/58561
VL  - 27
ER  -

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