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

Cancer Epidemiol Biomarkers Prev 2019 01 23;28(1):208-216. Epub 2018 Oct 23.

MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, United Kingdom.

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 ( < 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.

Download full-text PDF

Source
http://cebp.aacrjournals.org/lookup/doi/10.1158/1055-9965.EP
Publisher Site
http://dx.doi.org/10.1158/1055-9965.EPI-18-0079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6746173PMC
January 2019
27 Reads
4.125 Impact Factor

Publication Analysis

Top Keywords

prostate cancer
36
cancer
11
prostate
11
metabolites associated
8
metabolites prostate
8
associated prostate
8
circulating metabolites
8
appraise causality
8
cholesterol ratios
8
metabolites
7
ratios
6
genome practical
4
practical consortiumresults
4
consortiumresults thirty-five
4
thirty-five metabolites
4
cancer 00014
4
fell classes
4
lipoprotein subclass
4
subclass characteristics
4
characteristics total
4

Altmetric Statistics

Similar Publications