Mao Ziling, Baker Jacqueline Roshelli, Takeuchi Masayoshi, Hyogo Hideyuki, Tjønneland Anne, Eriksen Anne Kirstine, Severi Gianluca, Rothwell Joseph, Laouali Nasser, Katzke Verena, Kaaks Rudolf, Schulze Matthias B, Palli Domenico, Sieri Sabina, de Magistris Maria Santucci, Tumino Rosario, Sacerdote Carlotta, Derksen Jeroen W G, Gram Inger T, Skeie Guri, Sandanger Torkjel M, Quirós Jose Ramón, Crous-Bou Marta, Sánchez Maria-Jose, Amiano Pilar, Colorado-Yohar Sandra M, Guevara Marcela, Harlid Sophia, Johansson Ingegerd, Perez-Cornago Aurora, Freisling Heinz, Gunter Marc, Weiderpass Elisabete, Heath Alicia K, Aglago Elom, Jenab Mazda, Fedirko Veronika
Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Int J Cancer. 2023 Jun 1;152(11):2257-2268. doi: 10.1002/ijc.34449. Epub 2023 Mar 20.
Glyceraldehyde-derived advanced glycation end products (glycer-AGEs) could contribute to colorectal cancer development and progression due to their pro-oxidative and pro-inflammatory properties. However, the association of glycer-AGEs with mortality after colorectal cancer diagnosis has not been previously investigated. Circulating glycer-AGEs were measured by competitive ELISA. Multivariable Cox proportional hazards models were used to calculate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for associations of circulating glycer-AGEs concentrations with CRC-specific and all-cause mortality among 1034 colorectal cancer (CRC) cases identified within the European Prospective Investigation into Cancer and Nutrition (EPIC) study between 1993 and 2013. During a mean of 48 months of follow-up, 529 participants died (409 from CRC). Glycer-AGEs were statistically significantly positively associated with CRC-specific (HR = 1.53, 95% CI: 1.04-2.25, P = .002) and all-cause (HR = 1.62, 95% CI: 1.16-2.26, P < .001) mortality among individuals with CRC. There was suggestion of a stronger association between glycer-AGEs and CRC-specific mortality among patients with distal colon cancer (per SD increment: HR = 1.02, 95% CI: 0.74-1.42; HR = 1.51, 95% CI: 1.20-1.91; P = .02). The highest HR was observed among CRC cases in the highest body mass index (BMI) and glycer-AGEs category relative to lowest BMI and glycer-AGEs category for both CRC-specific (HR = 1.78, 95% CI: 1.02-3.01) and all-cause mortality (HR = 2.15, 95% CI: 1.33-3.47), although no statistically significant effect modification was observed. Our study found that prediagnostic circulating glycer-AGEs are positively associated with CRC-specific and all-cause mortality among individuals with CRC. Further investigations in other populations and stratifying by tumor location and BMI are warranted.
甘油醛衍生的晚期糖基化终产物（甘油-AGEs）因其促氧化和促炎特性，可能会促进结直肠癌的发生和发展。然而，此前尚未研究过甘油-AGEs与结直肠癌诊断后死亡率之间的关联。采用竞争性酶联免疫吸附测定法检测循环甘油-AGEs水平。在1993年至2013年欧洲癌症与营养前瞻性调查（EPIC）研究中确定的1034例结直肠癌（CRC）病例中，使用多变量Cox比例风险模型计算循环甘油-AGEs浓度与CRC特异性死亡率和全因死亡率之间关联的风险比（HR）及相应的95%置信区间（CI）。在平均48个月的随访期间，529名参与者死亡（409例死于CRC）。在CRC患者中，甘油-AGEs与CRC特异性死亡率（HR = 1.53，95%CI：1.04 - 2.25，P = 0.002）和全因死亡率（HR = 1.62，95%CI：1.16 - 2.26，P < 0.001）在统计学上呈显著正相关。对于远端结肠癌患者，甘油-AGEs与CRC特异性死亡率之间存在更强关联的迹象（每标准差增加：HR = 1.02，95%CI：0.74 - 1.42；HR = 1.51，95%CI：1.20 - 1.91；P = 0.02）。相对于最低体重指数（BMI）和甘油-AGEs类别，在最高BMI和甘油-AGEs类别的CRC病例中，观察到CRC特异性死亡率（HR = 1.78，95%CI：1.02 - 3.01）和全因死亡率（HR = 2.15，95%CI：1.33 - 3.47）的HR最高，尽管未观察到统计学上显著的效应修正。我们的研究发现，诊断前循环甘油-AGEs与CRC患者的CRC特异性死亡率和全因死亡率呈正相关。有必要在其他人群中进一步研究，并按肿瘤位置和BMI进行分层。
