Serum Metabolomic Profiling Of Prostate Cancer Risk In The Plco Cancer Screening Trial

Demetrius ALBANES, US National Cancer Institute, NIH, United States

1 Metabolic Epidemiology Branch, US National Cancer Institute, NIH, Bethesda, Maryland, US
2 University of Michigan School of Public Health, Ann Arbor, Michigan, US

Two recent analyses conducted within the ATBC Study identified serum metabolites related to risk of aggressive prostate cancer up to 20 years prior to diagnosis, including glycerophospholipids, fatty acids, inositol-1-phosphate, alpha-ketoglutarate, and citrate. The present investigation re-examined those associations in another cohort.
A nested case-control study of prostate cancer in the Prostate, Lung, Colorectal and Ovarian Cancer Screening (PLCO) Trial cohort was conducted with 380 cases and 380 controls matched on age, race, study center, and date of baseline blood collection.  Median time from baseline to prostate cancer diagnosis was 10.0 years (range, 4.4-17.0), and the majority of cases included here were diagnosed post-trial. Sera were analyzed on a high resolution accurate mass (HRAM) platform of ultrahigh performance LC-MS/GC-MS that identified 722 metabolites.  Logistic regression estimated odds ratios (OR) of risk associated with a one standard deviation (1-SD) increment in metabolite concentration.
Of the 27 metabolites associated with prostate cancer at p<0.05, 12 were amino acids or dipeptides, and amino acids as a chemical class was overrepresented among the top signals for stage 3-4 but not overall prostate cancer (p=0.003 and p=0.08).  Pyroglutamine, gamma-glutamylphenylalanine, phenylpyruvate, N-acetylcitrulline, and stearoylcarnitine yielded the strongest metabolite prostate cancer risk signals (1-SD increment ORs 0.78, 0.76, 0.73, 0.80, and 1.25, respectively; 0.001 < p < 0.006), including for aggressive disease.  Our earlier findings of inverse associations for the lipid and energy metabolites, and positive associations for TMAO and thyroxine, were not replicated.
Amino acids, and not lysolipids or TCA cycle metabolites, were prominently associated with prostate cancer in the present study.  Whether the PSA and digital rectal examination screenings in the trial, or the non-fasting status of the participants, contributed to the findings should be considered in future studies.
Funding source
Intramural research program of the US National Cancer Institute, NIH.