乙醛脱氢酶2基因rs671位点多态性与化疗所致的恶心呕吐相关

Aldehyde dehydrogenase 2 rs671 genetic polymorphisms are associated with chemotherapy-induced nausea and vomiting

目的探寻乙醛脱氢酶2(ALDH2)基因rs671位点单核苷酸多态性与化疗所致恶心呕吐的相关性。方法选择恶性肿瘤首次住院化疗的90例中国患者,多时段观察收集三联止呕方案下患者接受多西他赛联合顺铂化疗方案后120 h内化疗所致恶心呕吐(CINV)的发生情况。问卷采集所有患者的年龄、性别、肿瘤分期、习惯性饮酒、晕动症史、孕吐史、化疗前平均睡眠时间等的资料,并对其ALDH2基因rs671位点进行基因型检测。利用效用程序计算遗传连锁分析Hardy-Weinberg平衡检验。采用SPSS22.0分析ALDH2基因rs671位点多态性及其他因素与CINV间的关系。结果多西他赛联合顺铂化疗方案首次化疗恶性肿瘤患者CINV发生率为48.9%;单因素分析显示ALDH2基因rs671位点多态性与CINV相关(P<0.05);Logistic回归分析显示rs671位点突变型(OR:3.019,95%CI:1.056~8.628,P<0.05)、化疗前平均睡眠时间≤6 h(OR:2.807,95%CI:1.033~7.628,P<0.05)是影响多西他赛联合顺铂化疗方案首次化疗恶性肿瘤患者CINV发生情况的相关因素。结论ALDH2基因rs671位点突变是影响CINV发生情况的相关因素,需进一步明确其内在影响机制,以更加精准、有效地管控临床CINV发生情况。

Objective To investigate the correlation between aldehyde dehydrogenase 2(ALDH2)rs671 polymorphisms and chemotherapy-induced nausea and vomiting(CINV).Methods A total of 90 Chinese patients with malignant tumors receiving chemotherapy for the first time were recruited in this study.The occurrence of CINV was observed within 120 h after treatment with docetaxel and cis-platinum chemotherapy(DP regimen).The data of the patients(including age,gender,tumor stage,habitual alcohol consumption,motion sickness,morning sickness,and average sleep time prior to chemotherapy)were collected through a questionnaire.ALDH2 rs671 polymorphisms of the patients were analyzed using a multiple single nucleotide polymorphism genotyping,and the Hardy-Weinberg equation was used for genetic linkage analysis.The correlations between the factors including ALDH2 rs671 polymorphisms and the occurrence of CINV were analyzed.Results The incidence of CINV was 48.9%among the patients receiving their first chemotherapy with DP regimen.Univariate analysis indicated that the genetic polymorphisms of ALDH2 rs671 were significantly correlated with the occurrence of CINV(P<0.05).Multivariate logistic analysis indicated that ALDH2 rs671 mutation(OR:3.019,95%CI:1.056-8.628,P<0.05)and average sleep time prior to chemotherapy no longer than 6 h(OR:2.807,95%CI:1.033-7.628,P<0.05)were risk factors for CINV in patients with malignant tumors receiving the first chemotherapy with DP regimen.Conclusion ALDH2 gene mutation at rs671 is a risk factor contributing to the occurrence of CINV,and understanding of the underlying mechanism may help to more effectively control the occurrence of CINV.