Patterns in metabolite profile are associated with risk of more aggressive prostate cancer: A prospective study of 3,057 matched case-control sets from EPIC

Julie A Schmidt, Georgina K Fensom, Sabina Rinaldi, Augustin Scalbert, Paul N Appleby, David Achaintre, Audrey Gicquiau, Marc J Gunter, Pietro Ferrari, Rudolf Kaaks, Tilman Kühn, Heiner Boeing, Antonia Trichopoulou, Anna Karakatsani, Eleni Peppa, Domenico Palli, Sabina Sieri, Rosario Tumino, Bas Bueno-de-Mesquita, Antonio AgudoMaria-Jose Sánchez, María-Dolores Chirlaque, Eva Ardanaz, Nerea Larrañaga, Aurora Perez-Cornago, Nada Assi, Elio Riboli, Konstantinos K Tsilidis, Timothy J Key, Ruth C Travis

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Metabolomics may reveal novel insights into the etiology of prostate cancer, for which few risk factors are established. We investigated the association between patterns in baseline plasma metabolite profile and subsequent prostate cancer risk, using data from 3,057 matched case-control sets from the European Prospective Investigation into Cancer and Nutrition (EPIC). We measured 119 metabolite concentrations in plasma samples, collected on average 9.4 years before diagnosis, by mass spectrometry (AbsoluteIDQ p180 Kit, Biocrates Life Sciences AG). Metabolite patterns were identified using treelet transform, a statistical method for identification of groups of correlated metabolites. Associations of metabolite patterns with prostate cancer risk (OR1SD ) were estimated by conditional logistic regression. Supplementary analyses were conducted for metabolite patterns derived using principal component analysis and for individual metabolites. Men with metabolite profiles characterized by higher concentrations of either phosphatidylcholines or hydroxysphingomyelins (OR1SD  = 0.77, 95% confidence interval 0.66-0.89), acylcarnitines C18:1 and C18:2, glutamate, ornithine and taurine (OR1SD  = 0.72, 0.57-0.90), or lysophosphatidylcholines (OR1SD  = 0.81, 0.69-0.95) had lower risk of advanced stage prostate cancer at diagnosis, with no evidence of heterogeneity by follow-up time. Similar associations were observed for the two former patterns with aggressive disease risk (the more aggressive subset of advanced stage), while the latter pattern was inversely related to risk of prostate cancer death (OR1SD  = 0.77, 0.61-0.96). No associations were observed for prostate cancer overall or less aggressive tumor subtypes. In conclusion, metabolite patterns may be related to lower risk of more aggressive prostate tumors and prostate cancer death, and might be relevant to etiology of advanced stage prostate cancer.

Original languageEnglish
Pages (from-to)720-730
Number of pages11
JournalInternational Journal of Cancer
Issue number3
Early online date29 Apr 2019
Publication statusPublished - 01 Feb 2020

Bibliographical note

© 2019 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.


  • Aged
  • Biomarkers, Tumor/blood
  • Case-Control Studies
  • Follow-Up Studies
  • Humans
  • Male
  • Metabolomics
  • Middle Aged
  • Neoplasm Staging
  • Nutrition Assessment
  • Phosphatidylcholines/blood
  • Prospective Studies
  • Prostate/pathology
  • Prostatic Neoplasms/blood
  • Risk Factors
  • Sphingomyelins/blood


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