Analysis of Serum Metabolic Profiles in Women with Endometrial Cancer and Controls in a Population-Based Case-Control Study
Analysis of Serum Metabolic Profiles in Women with Endometrial Cancer and Controls in a Population-Based Case-Control Study
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DOI：
10.1210/jc.2012-1490
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发表时间：
2012-09-01
影响因子：
5.8
通讯作者：
Sherman, Mark E.
中科院分区：
文献类型：
--
作者：
Gaudet, Mia M.;Falk, Roni T.;Sherman, Mark E.
背景：子宫内膜癌与代谢紊乱有关，代谢紊乱与其潜在的危险因素有关，包括肥胖和糖尿病。鉴定与子宫内膜癌相关的代谢物生物标志物可能对早期检测、风险评估和了解病因学具有价值。目的：本研究的目的是评价非标准化血液采集的流行病学研究中代谢物的可靠测量;确认先前报道的代谢物与体型的相关性;并评估病例和对照组之间代谢物水平的差异。设计：这是波兰子宫内膜癌研究背景：本研究是一项基于人群的病例对照研究。患者：患者包括250例病例和250例对照。干预：干预包括测量15种氨基酸、45种酰基肉毒碱和9种脂肪酸的血清代谢物水平。主要结果测量：主要的结局指标是子宫内膜癌。体重指数与缬氨酸水平相关（r = 0.26，P = 3.4 × 10（-5）），辛烯酰-肉毒碱（r = 0.24，P = 1.5 × 10 ~（-4））、棕榈酸（r = 0.26，P = 4.4 × 10 ~（-5））、油酸（r = 0.28，P = 9.9 × 10 ~（-6））和硬脂酸（r = 0.26，P = 2.9 × 10 ~（-5））均高于对照组。只有硬脂酸与子宫内膜癌病例状态呈负相关（四分位数4与四分位数1：比值比0.37，95%置信区间0.20-0.69，趋势P = 1.2 x 10（-4））。C5-酰基肉毒碱，辛烯酰肉毒碱，decatrienoylcarnitine，亚油酸的水平显着低于对照组的情况下（比值比范围从0.21至0.38）。结论：这些数据表明，以前报道的代谢谱与体重指数的变化可以复制在以人群为基础的研究与非空腹采血协议。我们还提供了初步的证据，代谢物水平存在很大的差异的情况下，控制，独立的身体形态。我们的研究结果保证了在前瞻性收集的血液样本中评估代谢谱，包括本文确定的候选标志物，以定义与子宫内膜癌相关的生物标志物和病因学因素。（临床内分泌代谢杂志97：3216-3223，2012）
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 x 10(-5)), octenoyl-carnitine (r = 0.24, P = 1.5 x 10(-4)), palmitic acid (r = 0.26, P = 4.4 x 10(-5)), oleic acid (r = 0.28, P = 9.9 x 10(-6)), andstearic acid (r = 0.26, P = 2.9 x 10(-5)) amongcontrols. 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 x 10(-4)). Levels of the C5-acylcarnitines, octenoyl-carnitine, 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. (J Clin Endocrinol Metab 97: 3216-3223, 2012)