Dickerman Barbra A, Ebot Ericka M, Healy Brian C, Wilson Kathryn M, Eliassen A Heather, Ascherio Alberto, Pernar Claire H, Zeleznik Oana A, Vander Heiden Matthew G, Clish Clary B, Giovannucci Edward, Mucci Lorelei A
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
Department of Neurology, Harvard Medical School, Boston, MA 02115, USA.
Metabolites. 2020 Mar 10;10(3):99. doi: 10.3390/metabo10030099.
Obesity is associated with a higher risk of advanced prostate cancer, but men with the same body mass index (BMI) may differ in their underlying metabolic health. Using metabolomics data from nested case-control studies in the Health Professionals Follow-Up Study, we calculated Pearson correlations between 165 circulating metabolites and three adiposity measures (BMI, waist circumference, and derived fat mass from a validated prediction equation) to identify adiposity-associated metabolites. We used Lasso to further select metabolites for prediction models of adiposity measures, which we used to calculate metabolic scores representing metabolic obesity. In an independent set of 212 advanced prostate cancer cases (T3b/T4/N1/M1 or lethal during follow-up) and 212 controls, we used logistic regression to evaluate the associations between adiposity measures and metabolic scores with risk of advanced disease. All adiposity measures were associated with higher blood levels of carnitines (Pearson range, 0.16 to 0.18) and lower levels of glutamine ( = -0.19) and glycine ( -0.29 to -0.20), in addition to alterations in various lipids. No adiposity measure or metabolic score was associated with risk of advanced prostate cancer (e.g., odds ratio for a 5 kg/m increase in BMI 0.96 (95% CI: 0.73, 1.27) and BMI metabolic score 1.18 (95% CI: 0.57, 2.48)). BMI, waist circumference, and derived fat mass were associated with a broad range of metabolic alterations. Neither adiposity nor metabolic scores were associated with risk of advanced prostate cancer.
肥胖与晚期前列腺癌风险较高相关，但体重指数（BMI）相同的男性其潜在代谢健康状况可能存在差异。利用健康专业人员随访研究中巢式病例对照研究的代谢组学数据，我们计算了165种循环代谢物与三种肥胖指标（BMI、腰围以及通过验证的预测方程得出的脂肪量）之间的Pearson相关性，以识别与肥胖相关的代谢物。我们使用套索回归进一步选择用于肥胖指标预测模型的代谢物，并用这些模型计算代表代谢性肥胖的代谢评分。在一组由212例晚期前列腺癌病例（T3b/T4/N1/M1或随访期间致死）和212例对照组成的独立样本中，我们使用逻辑回归评估肥胖指标和代谢评分与晚期疾病风险之间的关联。除了各种脂质的改变外，所有肥胖指标均与较高的肉碱血水平（Pearson相关系数范围为0.16至0.18）以及较低的谷氨酰胺水平（=-0.19）和甘氨酸水平（-0.29至-0.20）相关。没有肥胖指标或代谢评分与晚期前列腺癌风险相关（例如，BMI每增加5kg/m²的比值比为0.96（95%CI：0.73，1.27），BMI代谢评分为1.18（95%CI：0.57，2.48））。BMI、腰围和得出的脂肪量与广泛的代谢改变相关。肥胖和代谢评分均与晚期前列腺癌风险无关。
