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结直肠癌患者诊断前血浆晚期糖基化终产物和可溶性晚期糖基化终产物受体与死亡率的关系。

Pre-diagnostic plasma advanced glycation end-products and soluble receptor for advanced glycation end-products and mortality in colorectal cancer patients.

机构信息

Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.

出版信息

Int J Cancer. 2024 Dec 1;155(11):1982-1995. doi: 10.1002/ijc.35114. Epub 2024 Jul 26.

Abstract

Advanced glycation end-products (AGEs), formed endogenously or obtained exogenously from diet, may contribute to chronic inflammation, intracellular signaling alterations, and pathogenesis of several chronic diseases including colorectal cancer (CRC). However, the role of AGEs in CRC survival is less known. The associations of pre-diagnostic circulating AGEs and their soluble receptor (sRAGE) with CRC-specific and overall mortality were estimated using multivariable-adjusted Cox proportional hazards regression among 1369 CRC cases in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Concentrations of major plasma AGEs, N-[carboxy-methyl]lysine (CML), N-[carboxy-ethyl]lysine (CEL) and N-[5-hydro-5-methyl-4-imidazolon-2-yl]-ornithine (MG-H1), were measured using ultra-performance liquid chromatography mass-spectrometry. sRAGE was assessed by enzyme-linked immunosorbent assay. Over a mean follow-up period of 96 months, 693 deaths occurred of which 541 were due to CRC. Individual and combined AGEs were not statistically significantly associated with CRC-specific or overall mortality. However, there was a possible interaction by sex for CEL (P = .05). Participants with higher sRAGE had a higher risk of dying from CRC (HR = 1.67, 95% CI: 1.21-2.30, P = .02) or any cause (HR = 1.38, 95% CI: 1.05-1.83, P = .09). These associations tended to be stronger among cases with diabetes (P = .03) and pre-diabetes (P <.01) before CRC diagnosis. Pre-diagnostic AGEs were not associated with CRC-specific and overall mortality in individuals with CRC. However, a positive association was observed for sRAGE. Our findings may stimulate further research on the role of AGEs and sRAGE in survival among cancer patients with special emphasis on potential effect modifications by sex and diabetes.

摘要

晚期糖基化终产物(AGEs),无论是内源性形成的还是外源性从饮食中获得的,都可能导致慢性炎症、细胞内信号改变,并导致几种慢性疾病的发病,包括结直肠癌(CRC)。然而,AGEs 在 CRC 生存中的作用知之甚少。在欧洲癌症前瞻性调查和营养研究(EPIC)中,对 1369 例 CRC 病例进行了多变量调整的 Cox 比例风险回归分析,以评估预诊断循环 AGEs 及其可溶性受体(sRAGE)与 CRC 特异性和总体死亡率的相关性。使用超高效液相色谱-质谱联用技术测量主要血浆 AGEs,N-[羧甲基]赖氨酸(CML)、N-[羧乙基]赖氨酸(CEL)和 N-[5-氢-5-甲基-4-咪唑啉-2-基]-鸟氨酸(MG-H1)的浓度。sRAGE 通过酶联免疫吸附试验进行评估。在平均 96 个月的随访期间,发生了 693 例死亡,其中 541 例死于 CRC。个体和组合的 AGEs 与 CRC 特异性或总体死亡率无统计学显著相关性。然而,CEL 存在性别交互作用(P=0.05)。具有较高 sRAGE 的参与者死于 CRC 的风险更高(HR=1.67,95%CI:1.21-2.30,P=0.02)或任何原因(HR=1.38,95%CI:1.05-1.83,P=0.09)。这些关联在 CRC 诊断前患有糖尿病(P=0.03)和糖尿病前期(P<.01)的病例中更为强烈。预诊断 AGEs 与 CRC 特异性和总体死亡率在患有 CRC 的个体中无相关性。然而,sRAGE 呈正相关。我们的发现可能会刺激进一步研究 AGEs 和 sRAGE 在癌症患者生存中的作用,特别强调性别和糖尿病的潜在效应修饰作用。

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