Abstract LB-454: Serum metabolic profiles and endometrial cancer
Authors: Gaudet Mia M. , Falk Roni , Stevens Robert D. , Pfeiffer Ruth , Potischman Nancy , Brinton Louise A. , Garcia-Closas Montserrat , Sherman Mark E. , Bain James R. , Muehlbauer Michael J. , Newgard Christopher B. , Gunter Marc J. , Lissowska Jolanta , Peplonska Beata 
Published: July 2012

Abstract
Obesity is a risk factor for endometrial cancer yet the molecular mechanism underlying this relationship is not fully understood. Obesity is associated with major metabolic changes; however, the relation between obesity and other endometrial cancer risk factors and alterations in circulating levels of specific metabolites have not been well-characterized in large population-based studies. We, therefore, measured circulating levels of major serum-based metabolites including 15 amino acids (AA), 45 acylcarnitines (AC), and 9 total fatty acids (FA) in 250 endometrial cancer cases and 250 population-based controls. Circulating levels of AA and AC were measured using flow-injection tandem mass spectrometry, and FAs were measured using gas chromatography/mass spectrometry. Initially, we assessed associations between metabolite levels and endometrial cancer risk factors among controls, and among cases evaluated metabolites by endometrial tumor characteristics. Comparisons of mean values by risk factors or tumor characteristics were performed using analysis of covariance, adjusted for age, study site, postprandial interval, and processing time. Multivariate logistic regression models were then used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations of circulating metabolites and risk of endometrial cancer adjusted for age, blood collection parameters, body mass index, and hormonally-related risk factors. Accounting for the multiple comparisons, p-values &lt;2.4×10−4 were considered significant. Levels of the branched chain AAs, leucine and isoleucine, were strongly, positively correlated with higher body mass index (p=3.7×10−11) in controls. Similar inverse trends were observed for isovaleryl carnitine (p=6.8×10−7) and linoleic acid (p=5.3×10−4), but not histidine (p=0.0021). Leucine/isoleucine levels were not associated with endometrial cancer risk. However, high levels of histidine were associated with lower risk of endometrial cancer (Q4 vs. Q1: OR=0.34, 95% CI 0.18–0.64; p for linear trend=1.07×10−6). Women with higher levels of isovaleryl carnitine, a catabolite of leucine, were at lower risk of endometrial cancer (OR=0.35, 95% CI 0.18–0.66; p=1.26×10−5). Linoleic acid levels were higher in cases than in controls (OR=0.19, 95% CI 0.10–0.37; p=8.33×10−7), and among cases, levels were higher in women with well differentiated tumors than women with moderately or poorly differentiated cancers (geometric means: 107.3, 87.1 and 88.9, respectively), although results were not statistically-significant (p=1.6×10−3). These data provide compelling evidence that metabolomic profiles may vary by endometrial cancer risk factors, and case-control status independent of obesity. Analysis of prospectively-collected blood samples are needed to determine whether metabolic profiles are etiologically related to endometrial cancer and can be used for risk prediction.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-454. doi:10.1158/1538-7445.AM2011-LB-454