Study On The Relationship Between ALDH2 Gene Polymorphism And Chemotherapy-induced Nausea And Vomiting

Purpose: To research the relationship between ALDH2 gene polymorphism and chemotherapy-induced nausea and vomiting(CINV),explore its influence on the levels of vomitogen neurotransmitters 5-HT and substance P,and analyze other risk factors for CINV.Methods:(1)A total of 90 patients with head and neck cancer and cervical cancer who received docetaxel combined with cisplatin in the first cycle of highly emetogenic chemotherapy were enrolled in this study,and the standard triple anti-emetosis regimen of Palonosetron,Aprepitant and dexamethasone were used in the study.(2)The occurrence of CINV in patients from day 1 to day 5 of chemotherapy was recorded,and the patient’s personal data including gender,age,tumor stage,history of carsickness,history of alcohol consumption,history of pregnancy reaction,and average sleep time during chemotherapy were collected to analyze the influence of patients’ personal factors on CINV.(3)Multiple SNP typing was used to detect the rs671 polymorphism of ALDH2 gene in patients before chemotherapy and analyze the effect of ALDH2 gene polymorphism on CINV.(4)Before chemotherapy and on the fifth day of chemotherapy,biochemical method was used to detect the total ALDH activity of patients,and enzymet-linked immunosorbent assay(ELISA)was used to detect the ALDH2 activity,ALDH2 content and the contents of the vomiting neurotransmitter 5-HT and substance P.The differences and changes of total ALDH activity,ALDH2 activity,ALDH2 content,5-HT content and substance P content were analyzed before and on the fifth day of chemotherapy.(5)In statistical analysis,the mean values of two independent samples were compared with independent sample T test,the chi-square test was used for rate comparison,Wilcoxon rank sum test was used for grade data,and single-factor and multi-factor binary Logistics regression analysis was used for risk factor screening.Results:(1)The incidence of CINV in docetaxel combined with cisplatin was 48.9%,acute CINV was 14.4%,and delayed CINV was47.8%.4.4% of patients experienced nausea with vomiting,and 48.9%experienced nausea.(2)ALDH2 wild type,mutant heterozygous type,mutant homozygous type(ALDH2*1/*1,ALDH2*1/*2,ALDH2*1/*2)accounted for 64.4%,32.2%,3.4%,respectively.The incidence of CINV between ALDH2 wild-type and mutant patients was 39.7% vs.65.6%(c2=5.566,p<0.05),and the incidence of acute CINV was 10.3% vs.21.9%(c2=2.218,p>0.05),and the incidence of delayed CINV was 39.7% vs.62.5%(c2=4.314,p<0.05).However,there was no significant difference in CINV grade between ALDH2 wild-type and mutant patients(p>0.05).(3)Univariate logistics regression analysis showed that female,had a history of motion sickness,average sleep duration during chemotherapy≤6h,a history of pregnancy reaction,no history of alcohol consumption,ALDH2 mutation was a risk factor for CINV.(4)Multivariate logistic regression analysis showed that ALDH2 gene mutation,average sleep time during chemotherapy ≤6h was an independent risk factor for CINV.(5)There were no significant differences in total ALDH activity,ALDH2 activity,ALDH2 content,5-HT content and substance P content between ALDH2 wild-type and ALDH2 mutant patients,patients with CINV and those without CINV before chemotherapy,5th day of chemotherapy and5 th day of chemotherapy(p>0.05).Conclusion:(1)ALDH2 gene polymorphism affects the occurrence of CINV,and ALDH2 mutant is an independent risk factor for CINV,mainly affecting the occurrence of delayed CINV.(2)Female,history of motion sickness,average sleep duration ≤6h during chemotherapy,history of pregnancy reaction,no history of alcohol consumption and ALDH2 gene mutation were risk factors for CINV.ALDH2 gene mutation and average sleep duration ≤6h during chemotherapy were independent risk factors for CINV.