刘秋霞?孙彩萍?叶万立?徐俊?朱晓灵?刘建江?孙红岗?王建芳

【摘要】目的 探討炎症因子与乳腺癌患者辅助放射治疗期间癌性疲劳的相关性。方法 选取术后辅助放射治疗的乳腺癌患者，按埃德蒙顿症状评估系统的疲劳评分将其分为疲劳组及观察组，比较2组血清炎症因子CRP、IL-6及可溶性肿瘤坏死因子受体2（sTNFR2）的差异;检测每位患者的疲劳相关炎症因子编码基因启动子的单核苷酸多态性，分析炎症因子相关基因分型与放射治疗结束时疲劳评分的相关性。结果 共61例患者入组，其中疲劳组37例。观察组24例，癌性疲劳的发生率为60.6%。疲劳组伴有恶心、焦虑及厌食者较观察组多（P均< 0.05）。疲劳组放射治疗后血清IL-6水平较治疗前高（P < 0.001），观察组放射治疗前、后IL-6水平比较差异无统计学意义（P > 0.05）。IL-6水平与疲劳的发生呈正相关（rs = 0.51，P < 0.001）。2组治疗前后CRP及sTNFR2水平比较差异均无统计学意义（P均> 0.05）。IL-6启动子编码基因IL6-174 GG基因分型的乳腺癌患者放射治疗结束时的疲劳评分高于CC基因分型患者（P = 0.001）。结论 血清IL-6水平及IL6-174 GG基因分型或与乳腺癌辅助放射治疗期间癌性疲劳的产生有关。

【关键词】炎症因子;癌性疲劳;白介素-6;IL6-174基因;乳腺癌

Correlation between inflammatory cytokines and cancer-related fatigue in breast cancer patients undergoing adjuvant radiotherapy Liu Qiuxia， Sun Caiping， Ye Wanli， Xu Jun， Zhu Xiaoling， Liu Jianjiang， Sun Honggang， Wang Jianfang. Shaoxing Peoples Hospital （Shaoxing Hospital of Zhejiang University）， Shao- xing 312000， China

Corresponding author， Wang Jianfang， E-mail： sxwxdd@ 163. com

【Abstract】Objective To investigate the correlation between inflammatory cytokines and cancer-related fatigue （CRF） in breast cancer patients undergoing adjuvant radiotherapy. Methods Breast cancer patients receiving postoperative adjuvant radiotherapy were recruited and divided into the fatigue group and observation group according to the fatigue score of Edmonton Symptom Assessment System. The differences of serum inflammatory cytokines of CRP， IL-6 and soluble tumor necrosis factor receptor-2 （sTNFR2） were statistically compared between two groups. The single nucleotide polymorphism of the genes encoding the inflammatory cytokines that were linked to CRF were also detected in each patient， and the relationship between genotyping and fatigue score was analyzed. Results Sixty one patients were enrolled，including 37 patients in the fatigue group and 24 cases in the control group. The incidence of CRF was 60.6%. The number of patients presenting with nausea， anxiety and lack of appetite in the fatigue group was significantly higher than that in the control group （all P < 0.05）. The serum concentration of IL-6 in the fatigue group was significantly increasedafter adjuvant radiotherapy （P < 0.001）， whereas the serum levels of IL-6 did not significantly differ before and after adjuvant radiotherapy in the control group （P > 0.05）. The serum level of IL-6 was positively correlated with the incidence of fatigue （rs = 0.51， P < 0.001）.The serum levels of CRP and sTNFR2 before and after corresponding treatment did not significantly differ between two groups （all P > 0.05）. Patients with GG genotyping of IL6-174 gene obtained significantly higher fatigue scores after radiotherapy compared with their counterparts with CC genotyping （P = 0.001）. Conclusion Serum IL-6 concentration and GG genotyping of IL6-174 gene are associated with the incidence of CRF in breast cancer patients during adjuvant radiotherapy.

【Key words】Inflammatory cytokine;Cancer-related fatigue;IL-6;IL6-174 gene;Breast cancer

疲劳是肿瘤患者常见的临床症状，癌性疲劳与肿瘤本身或肿瘤治疗有关，是一种持续性的疲劳状态[1]。癌性疲劳严重影响肿瘤患者的生活质量，其病理生理机制尚不明确，缺乏准确的检测方法。目前多项研究表明促炎症因子启动癌性疲劳，炎症因子的失调以及毒性下游效应可能是癌性疲劳及其他肿瘤相关症状（抑郁、睡眠障碍、疼痛、厌食等）的生物学基础[2]。有研究者发现外周促炎症因子通过作用于大脑基底神经节的特定区域引起疲劳及睡眠障碍、抑郁等症状[3]。……