Analysis of serum metabolic profiles in women with endometrial cancer and controls in a population-based case-control study

Mia M. Gaudet, Roni T. Falk, Robert D. Stevens, Marc J. Gunter, James R. Bain, Ruth M. Pfeiffer, Nancy Potischman, Jolanta Lissowska, Beata Peplonska, Louise A. Brinton, Montserrat Garcia-Closas, Christopher B. Newgard, Mark E. Sherman

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3216-3223
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume97
Issue number9
DOIs
StatePublished - Sep 2012

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Metabolome
Endometrial Neoplasms
Metabolites
Case-Control Studies
Serum
Population
Blood
Biomarkers
Body Mass Index
Odds Ratio
Outcome Assessment (Health Care)
Metabolomics
Palmitic Acid
Valine
Body Size
Linoleic Acid
Oleic Acid
Medical problems
Risk assessment
Epidemiologic Studies

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Medicine(all)
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Analysis of serum metabolic profiles in women with endometrial cancer and controls in a population-based case-control study. / Gaudet, Mia M.; Falk, Roni T.; Stevens, Robert D.; Gunter, Marc J.; Bain, James R.; Pfeiffer, Ruth M.; Potischman, Nancy; Lissowska, Jolanta; Peplonska, Beata; Brinton, Louise A.; Garcia-Closas, Montserrat; Newgard, Christopher B.; Sherman, Mark E.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 97, No. 9, 09.2012, p. 3216-3223.

Research output: Contribution to journalArticle

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 2012, 'Analysis of serum metabolic profiles in women with endometrial cancer and controls in a population-based case-control study', Journal of Clinical Endocrinology and Metabolism, vol. 97, no. 9, pp. 3216-3223. https://doi.org/10.1210/jc.2012-1490
Gaudet, Mia M. ; Falk, Roni T. ; Stevens, Robert D. ; Gunter, Marc J. ; Bain, James R. ; Pfeiffer, Ruth M. ; Potischman, Nancy ; Lissowska, Jolanta ; Peplonska, Beata ; Brinton, Louise A. ; Garcia-Closas, Montserrat ; Newgard, Christopher B. ; Sherman, Mark E. / Analysis of serum metabolic profiles in women with endometrial cancer and controls in a population-based case-control study. In: Journal of Clinical Endocrinology and Metabolism. 2012 ; Vol. 97, No. 9. pp. 3216-3223.
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AU - Gaudet, Mia M.

AU - Falk, Roni T.

AU - Stevens, Robert D.

AU - Gunter, Marc J.

AU - Bain, James R.

AU - Pfeiffer, Ruth M.

AU - Potischman, Nancy

AU - Lissowska, Jolanta

AU - Peplonska, Beata

AU - Brinton, Louise A.

AU - Garcia-Closas, Montserrat

AU - Newgard, Christopher B.

AU - Sherman, Mark E.

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N2 - 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.

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