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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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| Zeitschriftentitel: | Cancer Epidemiology, Biomarkers & Prevention |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , , , , , , , , , , , , |
| In: | Cancer Epidemiology, Biomarkers & Prevention, 27, 2018, 5, S. 531-540 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Association for Cancer Research (AACR)
|
| Schlagwörter: |
| author_facet |
Assi, Nada Thomas, Duncan C. Leitzmann, Michael Stepien, Magdalena Chajès, Véronique Philip, Thierry Vineis, Paolo Bamia, Christina Boutron-Ruault, Marie-Christine Sandanger, Torkjel M. Molinuevo, Amaia Boshuizen, Hendriek C. Sundkvist, Anneli Kühn, Tilman Travis, Ruth C. Overvad, Kim Riboli, Elio Gunter, Marc J. Scalbert, Augustin Jenab, Mazda Ferrari, Pietro Viallon, Vivian Assi, Nada Thomas, Duncan C. Leitzmann, Michael Stepien, Magdalena Chajès, Véronique Philip, Thierry Vineis, Paolo Bamia, Christina Boutron-Ruault, Marie-Christine Sandanger, Torkjel M. Molinuevo, Amaia Boshuizen, Hendriek C. Sundkvist, Anneli Kühn, Tilman Travis, Ruth C. Overvad, Kim Riboli, Elio Gunter, Marc J. Scalbert, Augustin Jenab, Mazda Ferrari, Pietro Viallon, Vivian |
|---|---|
| author |
Assi, Nada Thomas, Duncan C. Leitzmann, Michael Stepien, Magdalena Chajès, Véronique Philip, Thierry Vineis, Paolo Bamia, Christina Boutron-Ruault, Marie-Christine Sandanger, Torkjel M. Molinuevo, Amaia Boshuizen, Hendriek C. Sundkvist, Anneli Kühn, Tilman Travis, Ruth C. Overvad, Kim Riboli, Elio Gunter, Marc J. Scalbert, Augustin Jenab, Mazda Ferrari, Pietro Viallon, Vivian |
| spellingShingle |
Assi, Nada Thomas, Duncan C. Leitzmann, Michael Stepien, Magdalena Chajès, Véronique Philip, Thierry Vineis, Paolo Bamia, Christina Boutron-Ruault, Marie-Christine Sandanger, Torkjel M. Molinuevo, Amaia Boshuizen, Hendriek C. Sundkvist, Anneli Kühn, Tilman Travis, Ruth C. Overvad, Kim Riboli, Elio Gunter, Marc J. Scalbert, Augustin Jenab, Mazda Ferrari, Pietro Viallon, Vivian Cancer Epidemiology, Biomarkers & Prevention Are Metabolic Signatures Mediating the Relationship between Lifestyle Factors and Hepatocellular Carcinoma Risk? Results from a Nested Case–Control Study in EPIC Oncology Epidemiology |
| author_sort |
assi, nada |
| spelling |
Assi, Nada Thomas, Duncan C. Leitzmann, Michael Stepien, Magdalena Chajès, Véronique Philip, Thierry Vineis, Paolo Bamia, Christina Boutron-Ruault, Marie-Christine Sandanger, Torkjel M. Molinuevo, Amaia Boshuizen, Hendriek C. Sundkvist, Anneli Kühn, Tilman Travis, Ruth C. Overvad, Kim Riboli, Elio Gunter, Marc J. Scalbert, Augustin Jenab, Mazda Ferrari, Pietro Viallon, Vivian 1055-9965 1538-7755 American Association for Cancer Research (AACR) Oncology Epidemiology http://dx.doi.org/10.1158/1055-9965.epi-17-0649 <jats:title>Abstract</jats:title> <jats:p>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.</jats:p> <jats:p>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.</jats:p> <jats:p>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%.</jats:p> <jats:p>Conclusions: In a refined MITM framework, relevant metabolic signatures were identified as mediators in the relationship between lifestyle exposures and HCC risk.</jats:p> <jats:p>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 Epidemiol Biomarkers Prev; 27(5); 531–40. ©2018 AACR.</jats:p> 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 |
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American Association for Cancer Research (AACR), 2018 |
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| title |
Are Metabolic Signatures Mediating the Relationship between Lifestyle Factors and Hepatocellular Carcinoma Risk? Results from a Nested Case–Control Study in EPIC |
| title_unstemmed |
Are Metabolic Signatures Mediating the Relationship between Lifestyle Factors and Hepatocellular Carcinoma Risk? Results from a Nested Case–Control Study in EPIC |
| title_full |
Are Metabolic Signatures Mediating the Relationship between Lifestyle Factors and Hepatocellular Carcinoma Risk? Results from a Nested Case–Control Study in EPIC |
| title_fullStr |
Are Metabolic Signatures Mediating the Relationship between Lifestyle Factors and Hepatocellular Carcinoma Risk? Results from a Nested Case–Control Study in EPIC |
| title_full_unstemmed |
Are Metabolic Signatures Mediating the Relationship between Lifestyle Factors and Hepatocellular Carcinoma Risk? Results from a Nested Case–Control Study in EPIC |
| title_short |
Are Metabolic Signatures Mediating the Relationship between Lifestyle Factors and Hepatocellular Carcinoma Risk? Results from a Nested Case–Control Study in EPIC |
| title_sort |
are metabolic signatures mediating the relationship between lifestyle factors and hepatocellular carcinoma risk? results from a nested case–control study in epic |
| topic |
Oncology Epidemiology |
| url |
http://dx.doi.org/10.1158/1055-9965.epi-17-0649 |
| publishDate |
2018 |
| physical |
531-540 |
| description |
<jats:title>Abstract</jats:title>
<jats:p>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.</jats:p>
<jats:p>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.</jats:p>
<jats:p>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%.</jats:p>
<jats:p>Conclusions: In a refined MITM framework, relevant metabolic signatures were identified as mediators in the relationship between lifestyle exposures and HCC risk.</jats:p>
<jats:p>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 Epidemiol Biomarkers Prev; 27(5); 531–40. ©2018 AACR.</jats:p> |
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| author | Assi, Nada, Thomas, Duncan C., Leitzmann, Michael, Stepien, Magdalena, Chajès, Véronique, Philip, Thierry, Vineis, Paolo, Bamia, Christina, Boutron-Ruault, Marie-Christine, Sandanger, Torkjel M., Molinuevo, Amaia, Boshuizen, Hendriek C., Sundkvist, Anneli, Kühn, Tilman, Travis, Ruth C., Overvad, Kim, Riboli, Elio, Gunter, Marc J., Scalbert, Augustin, Jenab, Mazda, Ferrari, Pietro, Viallon, Vivian |
| author_facet | Assi, Nada, Thomas, Duncan C., Leitzmann, Michael, Stepien, Magdalena, Chajès, Véronique, Philip, Thierry, Vineis, Paolo, Bamia, Christina, Boutron-Ruault, Marie-Christine, Sandanger, Torkjel M., Molinuevo, Amaia, Boshuizen, Hendriek C., Sundkvist, Anneli, Kühn, Tilman, Travis, Ruth C., Overvad, Kim, Riboli, Elio, Gunter, Marc J., Scalbert, Augustin, Jenab, Mazda, Ferrari, Pietro, Viallon, Vivian, Assi, Nada, Thomas, Duncan C., Leitzmann, Michael, Stepien, Magdalena, Chajès, Véronique, Philip, Thierry, Vineis, Paolo, Bamia, Christina, Boutron-Ruault, Marie-Christine, Sandanger, Torkjel M., Molinuevo, Amaia, Boshuizen, Hendriek C., Sundkvist, Anneli, Kühn, Tilman, Travis, Ruth C., Overvad, Kim, Riboli, Elio, Gunter, Marc J., Scalbert, Augustin, Jenab, Mazda, Ferrari, Pietro, Viallon, Vivian |
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| description | <jats:title>Abstract</jats:title> <jats:p>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.</jats:p> <jats:p>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.</jats:p> <jats:p>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%.</jats:p> <jats:p>Conclusions: In a refined MITM framework, relevant metabolic signatures were identified as mediators in the relationship between lifestyle exposures and HCC risk.</jats:p> <jats:p>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 Epidemiol Biomarkers Prev; 27(5); 531–40. ©2018 AACR.</jats:p> |
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| spelling | Assi, Nada Thomas, Duncan C. Leitzmann, Michael Stepien, Magdalena Chajès, Véronique Philip, Thierry Vineis, Paolo Bamia, Christina Boutron-Ruault, Marie-Christine Sandanger, Torkjel M. Molinuevo, Amaia Boshuizen, Hendriek C. Sundkvist, Anneli Kühn, Tilman Travis, Ruth C. Overvad, Kim Riboli, Elio Gunter, Marc J. Scalbert, Augustin Jenab, Mazda Ferrari, Pietro Viallon, Vivian 1055-9965 1538-7755 American Association for Cancer Research (AACR) Oncology Epidemiology http://dx.doi.org/10.1158/1055-9965.epi-17-0649 <jats:title>Abstract</jats:title> <jats:p>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.</jats:p> <jats:p>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.</jats:p> <jats:p>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%.</jats:p> <jats:p>Conclusions: In a refined MITM framework, relevant metabolic signatures were identified as mediators in the relationship between lifestyle exposures and HCC risk.</jats:p> <jats:p>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 Epidemiol Biomarkers Prev; 27(5); 531–40. ©2018 AACR.</jats:p> 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 |
| spellingShingle | Assi, Nada, Thomas, Duncan C., Leitzmann, Michael, Stepien, Magdalena, Chajès, Véronique, Philip, Thierry, Vineis, Paolo, Bamia, Christina, Boutron-Ruault, Marie-Christine, Sandanger, Torkjel M., Molinuevo, Amaia, Boshuizen, Hendriek C., Sundkvist, Anneli, Kühn, Tilman, Travis, Ruth C., Overvad, Kim, Riboli, Elio, Gunter, Marc J., Scalbert, Augustin, Jenab, Mazda, Ferrari, Pietro, Viallon, Vivian, Cancer Epidemiology, Biomarkers & Prevention, Are Metabolic Signatures Mediating the Relationship between Lifestyle Factors and Hepatocellular Carcinoma Risk? Results from a Nested Case–Control Study in EPIC, Oncology, Epidemiology |
| title | Are Metabolic Signatures Mediating the Relationship between Lifestyle Factors and Hepatocellular Carcinoma Risk? Results from a Nested Case–Control Study in EPIC |
| title_full | Are Metabolic Signatures Mediating the Relationship between Lifestyle Factors and Hepatocellular Carcinoma Risk? Results from a Nested Case–Control Study in EPIC |
| title_fullStr | Are Metabolic Signatures Mediating the Relationship between Lifestyle Factors and Hepatocellular Carcinoma Risk? Results from a Nested Case–Control Study in EPIC |
| title_full_unstemmed | Are Metabolic Signatures Mediating the Relationship between Lifestyle Factors and Hepatocellular Carcinoma Risk? Results from a Nested Case–Control Study in EPIC |
| title_short | Are Metabolic Signatures Mediating the Relationship between Lifestyle Factors and Hepatocellular Carcinoma Risk? Results from a Nested Case–Control Study in EPIC |
| title_sort | are metabolic signatures mediating the relationship between lifestyle factors and hepatocellular carcinoma risk? results from a nested case–control study in epic |
| title_unstemmed | Are Metabolic Signatures Mediating the Relationship between Lifestyle Factors and Hepatocellular Carcinoma Risk? Results from a Nested Case–Control Study in EPIC |
| topic | Oncology, Epidemiology |
| url | http://dx.doi.org/10.1158/1055-9965.epi-17-0649 |