Department of Epidemiology, University of Kentucky, Lexington, KY, USA; Markey Cancer Center, University of Kentucky, Lexington, KY, USA.
Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA.
Metabolism. 2019 May;94:69-76. doi: 10.1016/j.metabol.2019.01.007. Epub 2019 Feb 23.
To investigate the association between biomarkers of inflammation and metabolic dysregulation and cancer mortality by obesity status.
Data from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort was used to examine the associations between baseline biomarkers of inflammation (IL-6, IL-8, IL-10, and CRP) and metabolism (adiponectin, resisting and lipoprotein (a)) with cancer mortality among 1822 participants cancer-free at baseline. Weighted Cox proportional hazard regression with the robust sandwich method was used to estimate the hazard ratios and 95% confidence intervals (CIs) adjusting for baseline covariates and stratified by BMI (normal, overweight/obese) given the significant interaction between biomarkers and BMI (p < 0.1).
During a mean follow-up of 8 years, there were statistically significant associations between cancer mortality and being in the highest vs. lowest tertile of IL-6 (HR: 5.3; 95% CI: 1.6, 17.8), CRP (HR: 3.4; 95% CI: 1.0, 11.2) and resistin (HR: 3.7; 95% CI: 1.2, 11.2) among participants with normal BMI. IL-6 was also associated with a 3-fold (HR: 3.5; 95% CI: 1.5, 8.1) increased risk of cancer mortality among participants with overweight/obesity; however, neither CRP nor resistin was significantly associated with cancer mortality in this group.
Higher baseline inflammatory and metabolic biomarkers were associated with significantly increased risk of cancer mortality after adjusting for baseline risk factors and the associations varied by BMI. Cancer patients may benefit from interventions that modulate inflammatory and metabolic biomarkers.
探讨炎症和代谢失调生物标志物与肥胖状态下癌症死亡率的关系。
本研究使用 Reasons for Geographic and Racial Differences in Stroke(REGARDS)队列的数据,来研究基线炎症生物标志物(IL-6、IL-8、IL-10 和 CRP)和代谢生物标志物(脂联素、抵抗素和脂蛋白(a))与基线时无癌症的 1822 名参与者的癌症死亡率之间的关系。鉴于生物标志物和 BMI 之间存在显著的交互作用(p<0.1),使用加权 Cox 比例风险回归和稳健 sandwich 方法来估计风险比和 95%置信区间(CI),并根据 BMI(正常、超重/肥胖)进行分层调整。
在平均 8 年的随访期间,在正常 BMI 的参与者中,与癌症死亡率呈统计学显著相关的标志物包括最高与最低三分位 IL-6(HR:5.3;95%CI:1.6,17.8)、CRP(HR:3.4;95%CI:1.0,11.2)和抵抗素(HR:3.7;95%CI:1.2,11.2)。IL-6 也与超重/肥胖参与者癌症死亡率增加 3 倍相关(HR:3.5;95%CI:1.5,8.1);然而,CRP 和抵抗素在这一组中与癌症死亡率均无显著相关性。
在调整基线风险因素后,较高的基线炎症和代谢生物标志物与癌症死亡率显著增加相关,且这种关联因 BMI 而异。癌症患者可能受益于调节炎症和代谢生物标志物的干预措施。