Huang Jiaqi, Mondul Alison M, Weinstein Stephanie J, Koutros Stella, Derkach Andriy, Karoly Edward, Sampson Joshua N, Moore Steven C, Berndt Sonja I, Albanes Demetrius
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda, MD, USA.
Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA.
Br J Cancer. 2016 Oct 25;115(9):1087-1095. doi: 10.1038/bjc.2016.305. Epub 2016 Sep 27.
Two recent metabolomic analyses found serum lipid, energy, and other metabolites related to aggressive prostate cancer risk up to 20 years prior to diagnosis.
We conducted a serum metabolomic investigation of prostate cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial that included annual serum total prostate-specific antigen measurement and digital rectal examination. This nested study included 380 cases diagnosed post-screening and 380 controls individually matched to cases on age, race, study centre, and blood-collection date (median time to diagnosis, 10 years (range 4.4-17 years)). Sera were analysed on a high-resolution accurate mass platform of ultrahigh-performance liquid and gas chromatography/mass spectroscopy that identified 695 known metabolites. Logistic regression conditioned on the matching factors estimated odds ratios (OR) and 95% confidence intervals of risk associated with an 80th percentile increase in the log-metabolite signal.
Twenty-seven metabolites were associated with prostate cancer at P<0.05. Pyroglutamine, gamma-glutamylphenylalanine, phenylpyruvate, N-acetylcitrulline, and stearoylcarnitine showed the strongest metabolite-risk signals (ORs=0.53, 0.51, 0.46, 0.58, and 1.74, respectively; 0.001⩽P⩽0.006). Findings were similar for aggressive disease (peptide chemical class, P=0.03). None of the P-values were below the threshold of Bonferroni correction, however.
A unique metabolomic profile associated with post-screening prostate cancer is identified that differs from that in a previously studied, unscreened population.
最近两项代谢组学分析发现，在诊断前长达20年的时间里，血清脂质、能量及其他代谢产物与侵袭性前列腺癌风险相关。
我们在前列腺、肺、结直肠癌和卵巢癌筛查试验中开展了一项血清代谢组学研究，以探究前列腺癌风险，该试验包括每年进行血清总前列腺特异性抗原检测和直肠指检。这项巢式研究纳入了380例筛查后确诊的病例以及380例对照，对照在年龄、种族、研究中心和采血日期方面与病例进行了个体匹配（诊断的中位时间为10年（范围4.4 - 17年））。血清在超高效液相和气相色谱/质谱联用的高分辨率精确质量平台上进行分析，该平台可识别695种已知代谢产物。基于匹配因素的逻辑回归估计了与对数代谢产物信号增加至第80百分位数相关的风险比值比（OR）和95%置信区间。
27种代谢产物与前列腺癌相关，P<0.05。焦谷氨酸、γ-谷氨酰苯丙氨酸、苯丙酮酸、N-乙酰瓜氨酸和硬脂酰肉碱显示出最强的代谢产物-风险信号（OR分别为0.53、0.51、0.46、0.58和1.74；0.001⩽P⩽0.006）。侵袭性疾病的结果相似（肽化学类别，P = 0.03）。然而，没有一个P值低于Bonferroni校正阈值。
确定了一种与筛查后前列腺癌相关的独特代谢组学特征，该特征与先前研究的未筛查人群不同。
