阻塞性睡眠呼吸暂停与肿瘤相关性Meta分析

Correlation between obstructive sleep apnea syndrome and tumor:A Meta-analysis

目的阻塞性睡眠呼吸暂停综合征(obstructive sleep apnea syndrome,OSAS)是一种全身性疾病,能够引起心、脑等多个器官损害,近年来有证据表明OSAS与肿瘤的发生发展相关。本研究探讨OSAS与肿瘤发生和侵袭的关系,尤其其主要病理生理学变化-慢性间歇低氧(chronic intermittent hypoxia,CIH)对肿瘤发生和发展的影响。方法检索PubMed、EMbase、Web of Science、万方数据库、维普数据和中国知网数据库,检索时间从建库至2017-04-30。按纳入与排除标准收集和整理动物实验和临床研究,筛选文献并进行质量评价,提取纳入文献中的相关信息后采用RevMan5.3软件进行Meta分析。结果共纳入动物实验文献5篇,包括实验动物183只;临床研究文献7篇,研究人群3 521 776例。Meta分析结果显示,与常氧对照组相比,CIH组小鼠肿瘤质量更重(WMD=0.66,95%CI:0.50~0.82,P<0.001),侵袭率更高(RR=2.97,95%CI:2.05~4.32,P<0.001)。OSAS患者发生肿瘤的风险较非OSAS人群更高,OR=1.53,95%CI:1.03~2.28,P=0.040。按地区分组,在亚洲人群中,OSAS患者肿瘤的发生率较非OSAS患者增高,OR=1.69,95%CI:1.15~2.49,P=0.007;在西方人群中,OSAS与肿瘤的发生无明显相关性,OR=1.38,95%CI:0.84~2.29,P=0.200。按诊断方法分组,与依靠临床诊断的OSAS患者相比,经标准睡眠监测(polysomnography,PSG)诊断的OSAS患者肿瘤发生率升高,OR=1.67,95%CI:1.39~2.02,P<0.001。结论 OSAS患者肿瘤发生率明显升高,其主要病理生理学变化-CIH可能是引起肿瘤发生和侵袭的机制。

OBJECTIVE Obstructive sleep apnea syndrome(OSAS)is a systemic disease which can cause multiple organ damage such as heart and brain.Recently,emerging evidence indicate that the possible association between OSAS and cancer.This systematic review aimed to investigate the relationship between the OSAS and the occurrence and invasion of tumor,especially focus on the effect of chronic intermittent hypoxia(the main pathophysiology of OSAS)on the occurrence and development of tumor.METHODS PubMed,EMbase,Web of Science,Wanfang database,VIP data and CNKI databases were searched for relevant studies in Chinese or English(from the date of the databases founded to April 2017).Both animal experiment and clinical studies were enrolled according to inclusive criteria.The quality of the included studies was evaluated and the relevant information was extracted.RevMan 5.3 software was used for Meta-analysis.RESULTS Of the 2186 retrieved citations,five animal studies(183 animals)and seven clinical trials defined OSAS using the apnea-hypopnea(AHI)or the respiratory disturbance index(RDI)(totally 1739296 patients with OSAS and 1782480 patients without OSAS)were pooled into meta-analysis.The results of Meta-analyses showed that tumor weight in chronic intermittent hypoxia(CIH)was heavier(WMD=0.66,95%CI:0.50-0.82,P<0.001)and the invasion rate was higher(RR=2.97,95%CI:2.05-4.32,P<0.001)than those in the normoxic group.The risk of tumor was also higher in OSAS patients than that in non-OSAS patients(OR=1.53,95% CI:1.03-2.28,P=0.040).The incidence of tumor increased in OSAS patients when compared to non-OSAS subjects in Asia(OR=1.69,95%CI:1.15-2.49,P=0.007),while there was no difference between OSAS and non-OSAS in the Western world(OR=1.38,95%CI:0.84-2.29,P=0.200).The incidence of tumor was higher in OSAS patients diagnosed by polysomnography(OR=1.67,95%CI:1.39-2.02,P<0.001),but not in those diagnosed by clinical symptom.CONCLUSION The incidence of tumor in OSAS patients is significantly higher.Chronic intermittent hypoxia may contribute to the increment of the tumor incidence and invasion.