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Circulating Metabolic Biomarkers of Screen-Detected Prostate Cancer in the ProtecT Study

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)208-216
Number of pages9
JournalCancer Epidemiology, Biomarkers and Prevention
Volume28
Issue number1
Early online date23 Oct 2018
DOIs
DateAccepted/In press - 15 Oct 2018
DateE-pub ahead of print - 23 Oct 2018
DatePublished (current) - Jan 2019

Abstract

BACKGROUND: Whether associations between circulating metabolites and prostate cancer are causal is unknown. We report on the largest study of metabolites and prostate cancer (2,291 cases and 2,661 controls) and appraise causality for a subset of the prostate cancer-metabolite associations using two-sample Mendelian randomization (MR).

METHODS: The case-control portion of the study was conducted in nine UK centers with men ages 50-69 years who underwent prostate-specific antigen screening for prostate cancer within the Prostate Testing for Cancer and Treatment (ProtecT) trial. Two data sources were used to appraise causality: a genome-wide association study (GWAS) of metabolites in 24,925 participants and a GWAS of prostate cancer in 44,825 cases and 27,904 controls within the Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium.

RESULTS: Thirty-five metabolites were strongly associated with prostate cancer ( P < 0.0014, multiple-testing threshold). These fell into four classes: (i) lipids and lipoprotein subclass characteristics (total cholesterol and ratios, cholesterol esters and ratios, free cholesterol and ratios, phospholipids and ratios, and triglyceride ratios); (ii) fatty acids and ratios; (iii) amino acids; (iv) and fluid balance. Fourteen top metabolites were proxied by genetic variables, but MR indicated these were not causal.

CONCLUSIONS: We identified 35 circulating metabolites associated with prostate cancer presence, but found no evidence of causality for those 14 testable with MR. Thus, the 14 MR-tested metabolites are unlikely to be mechanistically important in prostate cancer risk.

IMPACT: The metabolome provides a promising set of biomarkers that may aid prostate cancer classification.

    Structured keywords

  • ICEP
  • Centre for Surgical Research

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  • Full-text PDF (accepted author manuscript)

    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via AACR at http://cebp.aacrjournals.org/content/early/2018/10/23/1055-9965.EPI-18-0079 . Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 791 KB, PDF document

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