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癌症手术患者术后恶心呕吐相关的临床、种族和遗传风险因素:一项病例对照研究。

Clinical, ethnic and genetic risk factors associated with postoperative nausea and vomiting in patients undergoing cancer surgery: a case-control study.

作者信息

Grigio Thiago Ramos, Furuya Tatiane Katsue, Slullitel Alexandre, Murillo Carrasco Alexis Germán, Uno Miyuki, Alves Maria José Ferreira, Carmona Maria José Carvalho, Sugino Shigekazu, Chammas Roger, Sousa Angela Maria

机构信息

Postgraduate Program of Anaesthesiology, Surgical Sciences and Perioperative Medicine, Faculdade de Medicina da Universidade de São Paulo São Paulo, Brazil.

Department of Anaesthesiology, University of Groningen, University Medical Center Groningen Groningen, The Netherlands.

出版信息

Am J Transl Res. 2025 Apr 15;17(4):3235-3246. doi: 10.62347/DGRM3907. eCollection 2025.

Abstract

OBJECTIVES

To identify the clinical, ethnic, and genetic factors contributing to the varying risks of postoperative nausea and vomiting (PONV) among a Brazilian population undergoing cancer surgery.

METHODS

A case-control study was conducted involving 152 patients who experienced vomiting and/or retching (cases) and 158 patients who did not report nausea, vomiting, or retching (controls) within 24 h following oncological surgeries. This study is registered as 'Genetic Polymorphism and postoperative nausea and vomiting (PONV)' under registration number NCT03627780 (https://clinicaltrials.gov/study/NCT03627780). Thirty-two polymorphisms associated with PONV predisposition and 15 polymorphisms for ancestry analysis were genotyped via real-time polymerase chain reaction (PCR) with customised TaqMan low-density array (TLDA) cards.

RESULTS

The C allele of the rs208294 polymorphism ( gene) was observed at a significantly higher rate in the control group than in the case group across the genotype (P=0.035), dominant (P=0.010) and allele (0.032) models, thus suggesting a protective effect against PONV. The genotype results for rs208294 were validated via Sanger sequencing, which confirmed the association in the dominant model (P=0.027). In a multivariate regression analysis that included rs208294 and clinical variables that were identified in the univariate analysis, only a prior history of PONV or motion sickness was observed to be a significant predictor of PONV (P<0.05). No association between rs208294 and PONV was detected in an external cohort consisting of 198 cases and 56 controls of Japanese descents (P>0.05). Additionally, ancestry analysis indicated a predominantly European genetic composition in the Brazilian cohort, which differed with the Asian composition of the independent validation cohort.

CONCLUSIONS

A previous history of PONV or motion sickness was identified as being the strongest predictor of PONV in our analysis. Genetic association, ancestry and external validation analyses suggest that genetic factors for PONV may significantly differ across populations of different continental origins.

摘要

目的

确定在接受癌症手术的巴西人群中,导致术后恶心呕吐(PONV)风险各异的临床、种族和遗传因素。

方法

开展了一项病例对照研究,纳入152例在肿瘤手术后24小时内出现呕吐和/或干呕的患者(病例组)以及158例未报告恶心、呕吐或干呕的患者(对照组)。本研究已在“遗传多态性与术后恶心呕吐(PONV)”名下注册,注册号为NCT03627780(https://clinicaltrials.gov/study/NCT03627780)。通过使用定制的TaqMan低密度阵列(TLDA)卡进行实时聚合酶链反应(PCR),对32个与PONV易感性相关的多态性位点以及15个用于血统分析的多态性位点进行基因分型。

结果

在基因型(P = 0.035)、显性模型(P = 0.010)和等位基因模型(P = 0.032)中,对照组rs208294多态性位点(基因)的C等位基因出现率均显著高于病例组,表明其对PONV具有保护作用。rs208294的基因型结果通过桑格测序法进行验证,证实了显性模型中的关联(P = 0.027)。在一项纳入rs208294和单变量分析中确定的临床变量的多变量回归分析中,仅观察到PONV或晕动病既往史是PONV的显著预测因素(P < 0.05)。在一个由198例病例和56例日本裔对照组成的外部队列中,未检测到rs208294与PONV之间的关联(P > 0.05)。此外,血统分析表明巴西队列主要为欧洲遗传组成,这与独立验证队列的亚洲组成不同。

结论

在我们的分析中,PONV或晕动病既往史被确定为PONV最强的预测因素。遗传关联、血统和外部验证分析表明,不同大陆起源人群中PONV的遗传因素可能存在显著差异。

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