Serum Metabolomic Profiling of All-Cause Mortality: A Prospective Analysis in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study Cohort

Authors

• J Huang
• SJ Weinstein
• SC Moore
• A Derkach
• X Hua
• LM Liao
• F Gu
• AM Mondul
• JN Sampson
• D Albanes

Abstract

Background: Tobacco use, hypertension, hyperglycemia, overweight, and inactivity are leading causes of mortality worldwide, yet specific relevant metabolic alterations are largely unknown. Methods: We conducted a serum metabolomic analysis of 620 men in the ATBC Study. During 28 years of follow-up, there were 435 deaths, including 197 from cardiovascular disease (CVD) and 107 from cancer. The analysis included 406 known metabolites measured with ultra-high performance LC/MS and GC/MS. We used Cox regression to estimate mortality hazard ratios (HR) for a one standard-deviation (SD) difference in the metabolite-signal, subsequently divided the data into training and test sets, and used the former to create a metabolite risk score of the strongest metabolites (false discovery rate [FDR]< 0.1) to apply to the test-set. Results: The strongest associations with overall mortality were N-acetylvaline (HR=1.28; P

Scientific Focus Area: Epidemiology

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