儿童癌症治疗后异常的高密度脂蛋白脂质和蛋白组成：一项关联研究。

Abnormal HDL lipid and protein composition following pediatric cancer treatment: an associative study.

机构信息

Research Centre, CHU Sainte-Justine, 3175 Chem. de la Côte-Sainte-Catherine, Montreal, QC, H3T 1C5, Canada.

Department of Nutrition, Université de Montréal, Montreal, QC, Canada.

出版信息

Lipids Health Dis. 2023 Jun 10;22(1):72. doi: 10.1186/s12944-023-01822-2.

DOI:10.1186/s12944-023-01822-2

PMID:37301877

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10257312/

Abstract

BACKGROUND

Long-term childhood cancer survivors (CCS) are at high risk of having dyslipidemia including low high density lipoprotein cholesterol (HDL-C). However, little is known about the prevalence of low HDL-C and the impact of therapy exposure on HDL composition early after treatment is terminated.

METHODS

This associative study included 50 children and adolescents who had completed their cancer treatments (< 4 years). Clinical characteristics (demographic, diagnosis, treatment, anthropometric parameters), fasting plasma lipids, apoliporoteins (Apo) A-I and composition of HDL fractions (HDL2 and HDL3) were assessed. Data were stratified according to the presence of dyslipidemia and median doses of therapeutic agents and compared using Fisher exact or Mann-Whitney tests. Univariate binary logistic regression analyses were carried out to evaluate the associations between the clinical and biochemical characteristics and having low HDL-C. Composition of HDL2 and HDL3 particles was assessed in a sub-group of 15 patients and compared to 15 age- and sex-matched healthy controls using Wilcoxon paired test.

RESULTS

Of the 50 pediatric cancer patients included in this study (mean age: 11.30 ± 0.72 y; mean time since end of treatment: 1.47 ± 0.12 y; male: 38%), 8 had low HDL-C (16%), all of which were adolescent at diagnosis. Higher doses of doxorubicin were associated with lower HDL-C and Apo A-I levels. In hypertriglyceridemic patients and compared to normolipidemics, triglycerides (TG) content was greater in HDL2 and HDL3 fractions whereas esterified cholesterol (EC) content was lower in HDL2. Enrich TG content of HDL3 and lower EC of HDL2 was found in patients exposed to ≥ 90 mg/m doxorubicin. Factors positively associated with the risk of having low HDL-C were age, being overweight or obese and exposure to doxorubicin ≥ 90 mg/m. Compared to healthy controls, a sub-group of 15 patients showed higher TG and free cholesterol (FC) content of HDL2 and HDL3 and lower EC content in HDL3.

CONCLUSIONS

Overall, we found abnormalities in HDL-C and Apo A-I levels and in HDL composition early after pediatric cancer treatment that are influenced by age, overweight or obesity status and exposure to doxorubicin.

摘要

背景

长期儿童癌症幸存者（CCS）存在血脂异常的风险较高，包括低高密度脂蛋白胆固醇（HDL-C）。然而，关于治疗结束后早期低 HDL-C 的患病率以及治疗暴露对 HDL 组成的影响知之甚少。

方法

本关联研究纳入了 50 名完成癌症治疗（<4 年）的儿童和青少年。评估了临床特征（人口统计学、诊断、治疗、人体测量参数）、空腹血浆脂质、载脂蛋白（Apo）A-I 和 HDL 分数（HDL2 和 HDL3）的组成。根据血脂异常的存在和治疗药物的中位剂量对数据进行分层，并使用 Fisher 精确检验或 Mann-Whitney 检验进行比较。进行单变量二元逻辑回归分析，以评估临床和生化特征与低 HDL-C 之间的关联。对 15 名患者的 HDL2 和 HDL3 颗粒组成进行亚组评估，并与 15 名年龄和性别匹配的健康对照者进行比较，采用 Wilcoxon 配对检验。

结果

在本研究中纳入的 50 名儿科癌症患者（平均年龄：11.30±0.72 岁；治疗结束后平均时间：1.47±0.12 年；男性：38%）中，有 8 人（16%）存在低 HDL-C，均为诊断时的青少年。阿霉素剂量较高与 HDL-C 和 Apo A-I 水平降低相关。与血脂正常者相比，在高甘油三酯血症患者中，HDL2 和 HDL3 中的甘油三酯（TG）含量较高，而 HDL2 中的酯化胆固醇（EC）含量较低。在接受≥90mg/m 阿霉素治疗的患者中，发现 HDL3 的 TG 含量增加，HDL2 的 EC 含量降低。与低 HDL-C 风险相关的因素有年龄、超重或肥胖以及接受阿霉素治疗≥90mg/m。与健康对照组相比，15 名患者的亚组中 HDL2 和 HDL3 的 TG 和游离胆固醇（FC）含量较高，HDL3 的 EC 含量较低。