期刊
BRITISH JOURNAL OF CANCER
卷 115, 期 9, 页码 1087-1095出版社
SPRINGERNATURE
DOI: 10.1038/bjc.2016.305
关键词
prostate cancer; metabolomic profiling; aggressive; pre-diagnosed serum; pyroglutamine; gamma-glutamyl peptides; N-acetyl amino acids; fatty acids
类别
资金
- Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH [Z01-CP010119, ZIA-CP010152-11]
Background: Two recent metabolomic analyses found serum lipid, energy, and other metabolites related to aggressive prostate cancer risk up to 20 years prior to diagnosis. Methods: We conducted a serum metabolomic investigation of prostate cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial that included annual serum total prostate-specific antigen measurement and digital rectal examination. This nested study included 380 cases diagnosed post-screening and 380 controls individually matched to cases on age, race, study centre, and blood-collection date (median time to diagnosis, 10 years (range 4.4-17 years)). Sera were analysed on a highr-resolution accurate mass platform of ultrahigh-performance liquid and gas chromatography/mass spectroscopy that identified 695 known metabolites. Logistic regression conditioned on the matching factors estimated odds ratios (OR) and 95% confidence intervals of risk associated with an 80th percentile increase in the log-metabolite signal. Results: Twenty-seven metabolites were associated with prostate cancer at P<0.05. Pyroglutamine, gamma-glutamylphenylalanine, phenylpyruvate, N-acetylcitrulline, and stearoylcarnitine showed the strongest metabolite-risk signals (ORs = 0.53, 0.51, 0.46, 0.58, and 1.74, respectively; 0.001 <= P <= 0.006). Findings were similar for aggressive disease (peptide chemical class, P = 0.03). None of the P-values were below the threshold of Bonferroni correction, however. Conclusions: A unique metabolomic profile associated with post-screening prostate cancer is identified that differs from that in a previously studied, unscreened population.
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