Analysis of serum metabolic profiles in women with endometrial cancer and controls in a population-based case-control study.
CONTEXT: Endometrial cancer is associated with metabolic disturbances related to its underlying risk factors, including obesity and diabetes. Identifying metabolite biomarkers associated with endometrial cancer may have value for early detection, risk assessment, and understanding etiology. OBJECTIVE: The objective of the study was to evaluate the reliable measurement of metabolites in epidemiological studies with nonstandardized blood collection; confirm previously reported correlations of metabolites with body size; and assess differences in metabolite levels between cases and controls. DESIGN: This was the Polish Endometrial Cancer Study (2001-2003). SETTING: This study was a population-based case-control study. PATIENTS: Patients included 250 cases and 250 controls. INTERVENTION: The intervention included the measurement of serum metabolite levels of 15 amino acids, 45 acylcarnitines, and nine fatty acids. MAIN OUTCOME MEASURE: The main outcome measure was endometrial cancer. RESULTS: Body mass index was correlated with levels of valine (r = 0.26, P = 3.4 × 10(-5)), octenoylcarnitine (r = 0.24, P = 1.5 × 10(-4)), palmitic acid (r = 0.26, P = 4.4 × 10(-5)), oleic acid (r = 0.28, P = 9.9 × 10(-6)), and stearic acid (r = 0.26, P = 2.9 × 10(-5)) among controls. Only stearic acid was inversely associated with endometrial cancer case status (quartile 4 vs. quartile 1: odds ratio 0.37, 95% confidence interval 0.20-0.69, P for trend = 1.2 × 10(-4)). Levels of the C5-acylcarnitines, octenoylcarnitine, decatrienoylcarnitine, and linoleic acid were significantly lower in cases than controls (odds ratios ranged from 0.21 to 0.38). CONCLUSIONS: These data demonstrate that previously reported variations in metabolomic profiles with body mass index can be replicated in population-based studies with nonfasting blood collection protocols. We also provide preliminary evidence that large differences in metabolite levels exist between cases and controls, independent of body habitus. Our findings warrant assessment of metabolic profiles, including the candidate markers identified herein, in prospectively collected blood samples to define biomarkers and etiological factors related to endometrial cancer.
Gaudet, MM; Falk, RT; Stevens, RD; Gunter, MJ; Bain, JR; Pfeiffer, RM; Potischman, N; Lissowska, J; Peplonska, B; Brinton, LA; Garcia-Closas, M; Newgard, CB; Sherman, ME
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