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Are Metabolic Signa...
Are Metabolic Signatures Mediating the Relationship between Lifestyle Factors and Hepatocellular Carcinoma Risk? Results from a Nested Case–Control Study in EPIC
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Assi, Nada (author)
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Thomas, Duncan C. (author)
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Leitzmann, Michael (author)
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Stepien, Magdalena (author)
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Chajès, Véronique (author)
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Philip, Thierry (author)
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Vineis, Paolo (author)
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Bamia, Christina (author)
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Boutron-Ruault, Marie-Christine (author)
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Sandanger, Torkjel M. (author)
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Molinuevo, Amaia (author)
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Boshuizen, Hendriek C. (author)
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- Sundkvist, Anneli (author)
- Umeå universitet,Onkologi
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Kühn, Tilman (author)
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Travis, Ruth C. (author)
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Overvad, Kim (author)
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Riboli, Elio (author)
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Gunter, Marc J. (author)
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Scalbert, Augustin (author)
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Jenab, Mazda (author)
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Ferrari, Pietro (author)
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Viallon, Vivian (author)
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(creator_code:org_t)
- 2018
- 2018
- English.
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In: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 27:5, s. 531-540
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- 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 mediators.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Hälsovetenskap -- Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Health Sciences -- Public Health, Global Health, Social Medicine and Epidemiology (hsv//eng)
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- ref (subject category)
- art (subject category)
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- By the author/editor
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Assi, Nada
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Thomas, Duncan C ...
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Leitzmann, Micha ...
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Stepien, Magdale ...
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Chajès, Véroniqu ...
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Philip, Thierry
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show more...
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Vineis, Paolo
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Bamia, Christina
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Boutron-Ruault, ...
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Sandanger, Torkj ...
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Molinuevo, Amaia
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Boshuizen, Hendr ...
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Sundkvist, Annel ...
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Kühn, Tilman
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Travis, Ruth C.
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Overvad, Kim
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Riboli, Elio
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Gunter, Marc J.
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Scalbert, August ...
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Jenab, Mazda
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Ferrari, Pietro
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Viallon, Vivian
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Health Sciences
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and Public Health Gl ...
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Cancer Epidemiol ...
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Umeå University