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Open Access 01-12-2022 | Prostate Cancer | Research article

Pan-cancer analysis of pre-diagnostic blood metabolite concentrations in the European Prospective Investigation into Cancer and Nutrition

Authors: Marie Breeur, Pietro Ferrari, Laure Dossus, Mazda Jenab, Mattias Johansson, Sabina Rinaldi, Ruth C. Travis, Mathilde His, Tim J. Key, Julie A. Schmidt, Kim Overvad, Anne Tjønneland, Cecilie Kyrø, Joseph A. Rothwell, Nasser Laouali, Gianluca Severi, Rudolf Kaaks, Verena Katzke, Matthias B. Schulze, Fabian Eichelmann, Domenico Palli, Sara Grioni, Salvatore Panico, Rosario Tumino, Carlotta Sacerdote, Bas Bueno-de-Mesquita, Karina Standahl Olsen, Torkjel Manning Sandanger, Therese Haugdahl Nøst, J. Ramón Quirós, Catalina Bonet, Miguel Rodríguez Barranco, María-Dolores Chirlaque, Eva Ardanaz, Malte Sandsveden, Jonas Manjer, Linda Vidman, Matilda Rentoft, David Muller, Kostas Tsilidis, Alicia K. Heath, Hector Keun, Jerzy Adamski, Pekka Keski-Rahkonen, Augustin Scalbert, Marc J. Gunter, Vivian Viallon

Published in: BMC Medicine | Issue 1/2022

Abstract

Background

Epidemiological studies of associations between metabolites and cancer risk have typically focused on specific cancer types separately. Here, we designed a multivariate pan-cancer analysis to identify metabolites potentially associated with multiple cancer types, while also allowing the investigation of cancer type-specific associations.

Methods

We analysed targeted metabolomics data available for 5828 matched case-control pairs from cancer-specific case-control studies on breast, colorectal, endometrial, gallbladder, kidney, localized and advanced prostate cancer, and hepatocellular carcinoma nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. From pre-diagnostic blood levels of an initial set of 117 metabolites, 33 cluster representatives of strongly correlated metabolites and 17 single metabolites were derived by hierarchical clustering. The mutually adjusted associations of the resulting 50 metabolites with cancer risk were examined in penalized conditional logistic regression models adjusted for body mass index, using the data-shared lasso penalty.

Results

Out of the 50 studied metabolites, (i) six were inversely associated with the risk of most cancer types: glutamine, butyrylcarnitine, lysophosphatidylcholine a C18:2, and three clusters of phosphatidylcholines (PCs); (ii) three were positively associated with most cancer types: proline, decanoylcarnitine, and one cluster of PCs; and (iii) 10 were specifically associated with particular cancer types, including histidine that was inversely associated with colorectal cancer risk and one cluster of sphingomyelins that was inversely associated with risk of hepatocellular carcinoma and positively with endometrial cancer risk.

Conclusions

These results could provide novel insights for the identification of pathways for cancer development, in particular those shared across different cancer types.

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Title: Pan-cancer analysis of pre-diagnostic blood metabolite concentrations in the European Prospective Investigation into Cancer and Nutrition
Authors: Marie Breeur
Pietro Ferrari
Laure Dossus
Mazda Jenab
Mattias Johansson
Sabina Rinaldi
Ruth C. Travis
Mathilde His
Tim J. Key
Julie A. Schmidt
Kim Overvad
Anne Tjønneland
Cecilie Kyrø
Joseph A. Rothwell
Nasser Laouali
Gianluca Severi
Rudolf Kaaks
Verena Katzke
Matthias B. Schulze
Fabian Eichelmann
Domenico Palli
Sara Grioni
Salvatore Panico
Rosario Tumino
Carlotta Sacerdote
Bas Bueno-de-Mesquita
Karina Standahl Olsen
Torkjel Manning Sandanger
Therese Haugdahl Nøst
J. Ramón Quirós
Catalina Bonet
Miguel Rodríguez Barranco
María-Dolores Chirlaque
Eva Ardanaz
Malte Sandsveden
Jonas Manjer
Linda Vidman
Matilda Rentoft
David Muller
Kostas Tsilidis
Alicia K. Heath
Hector Keun
Jerzy Adamski
Pekka Keski-Rahkonen
Augustin Scalbert
Marc J. Gunter
Vivian Viallon
Publication date: 01-12-2022
Publisher: BioMed Central
Keywords: Prostate Cancer
Nutrition
Prostate Cancer
Hepatocellular Carcinoma
Hepatocellular Carcinoma
Colorectal Cancer
Colorectal Cancer
Endometrial Cancer
Endometrial Cancer
Published in: BMC Medicine / Issue 1/2022
Electronic ISSN: 1741-7015
DOI: https://doi.org/10.1186/s12916-022-02553-4

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Pan-cancer analysis of pre-diagnostic blood metabolite concentrations in the European Prospective Investigation into Cancer and Nutrition

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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