Remnant cholesterol and systemic inflammation as synergistic predictors of cancer risk: A 16-year prospective cohort study

IF 5.1 2区医学 Q1 ONCOLOGY

Cancer Pub Date : 2025-09-18 DOI:10.1002/cncr.70096

Hongxue Xu MD, Peipei Liu MD, Shuohua Chen PhD, Guodong Wang MM, Shouling Wu MD, Xuemei Zhang PhD

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引用次数: 0

Abstract

Background

Remnant cholesterol (RC), a marker of triglyceride-rich lipoproteins, has been implicated in cardiovascular disease via inflammatory pathways, but its role in cancer development remains unclear. This study investigated the independent and joint effects of RC and systemic inflammation on long-term cancer risk.

Methods

The authors analyzed data from 136,158 participants in the Kailuan cohort who were free from cancer and cardiovascular disease at baseline. RC was calculated as total cholesterol minus high-density lipoprotein cholesterol and low-density lipoprotein cholesterol. High-sensitivity C-reactive protein (hs-CRP) was used to assess systemic inflammation. Incident cancer cases were identified during a median follow-up of 16.18 years. Cox proportional hazards models, interaction analyses, mediation analysis, and cross-lagged panel models were used to assess the relationships between RC, hs-CRP, and cancer.

Results

A total of 7080 incident cancers were recorded. Compared with the lowest quartile of RC (Q1), participants in the highest quartile (Q4) had a significantly increased risk of overall cancer (hazard ratio [HR], 1.188; 95% confidence interval [CI], 1.108–1.273), lung cancer (HR, 1.349; 95% CI, 1.179–1.543), and colorectal cancer (HR, 1.775; 95% CI, 1.443–2.184). Participants with both high RC and high hs-CRP had the highest risk (HR, 1.332; 95% CI, 1.268–1.400). Mediation analysis revealed that RC mediated 8.31% of the hs-CRP–cancer relationship, and vice versa. Cross-lagged models confirmed a bidirectional temporal association.

Conclusion

RC and systemic inflammation act synergistically and bidirectionally to increase cancer risk, supporting a metabolic–inflammatory axis in carcinogenesis. These findings identify novel, potentially modifiable targets for early cancer risk stratification and prevention.

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残余胆固醇和全身性炎症作为癌症风险的协同预测因子：一项16年的前瞻性队列研究

背景：残余胆固醇（RC）是一种富含甘油三酯的脂蛋白标志物，通过炎症途径与心血管疾病有关，但其在癌症发展中的作用尚不清楚。本研究探讨了RC和全身性炎症对长期癌症风险的独立和联合影响。方法：作者分析了来自开滦队列的136158名参与者的数据，他们在基线时没有癌症和心血管疾病。RC计算为总胆固醇减去高密度脂蛋白胆固醇和低密度脂蛋白胆固醇。采用高敏c反应蛋白（hs-CRP）评估全身性炎症。在中位16.18年的随访期间确定了偶发性癌症病例。采用Cox比例风险模型、相互作用分析、中介分析和交叉滞后面板模型来评估RC、hs-CRP和癌症之间的关系。结果：共记录了7080例癌症。与RC的最低四分位数（Q1）相比，最高四分位数（Q4）的参与者患总体癌症的风险显著增加（风险比[HR]， 1.188； 95%可信区间[CI]， 1.108-1.273），肺癌（HR, 1.349; 95% CI, 1.179-1.543），结直肠癌（HR, 1.775; 95% CI, 1.443-2.184）。高RC和高hs-CRP的参与者风险最高（HR, 1.332; 95% CI, 1.268-1.400）。中介分析显示，RC介导了8.31%的hs-CRP-cancer关系，反之亦然。交叉滞后模型证实了一种双向时间关联。结论：RC和全身性炎症协同作用，双向增加癌症风险，在癌变过程中支持代谢-炎症轴。这些发现为早期癌症风险分层和预防确定了新的、潜在的可改变的靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer 医学-肿瘤学

CiteScore

13.10

自引率

3.20%

发文量

480

审稿时长

2-3 weeks

期刊介绍： The CANCER site is a full-text, electronic implementation of CANCER, an Interdisciplinary International Journal of the American Cancer Society, and CANCER CYTOPATHOLOGY, a Journal of the American Cancer Society. CANCER publishes interdisciplinary oncologic information according to, but not limited to, the following disease sites and disciplines: blood/bone marrow; breast disease; endocrine disorders; epidemiology; gastrointestinal tract; genitourinary disease; gynecologic oncology; head and neck disease; hepatobiliary tract; integrated medicine; lung disease; medical oncology; neuro-oncology; pathology radiation oncology; translational research