» Articles » PMID: 37924126

A Randomized Trial Evaluating the Association Between Related Gene Polymorphism and Nausea and Vomiting Induced by Cisplatin Multi-day Chemotherapy

Overview
Publisher Biomed Central
Specialty Genetics
Date 2023 Nov 4
PMID 37924126
Authors
Affiliations
Soon will be listed here.
Abstract

Purpose: We aim to investigate the correlation between gene polymorphisms and cisplatin chemotherapy-induced nausea and vomiting (CINV), which was prevented by olanzapine or aprepitant triple antiemetic regimen.

Methods: Before chemotherapy, the blood samples of 89 malignant tumor patients who received multi-day chemotherapy with cisplatin were collected for sequencing and typing. As there were duplicate patients enrolled in different chemotherapy cycles, there were a total of 190 cases. The patients were divided into two groups randomly, who received the triple antiemetic regimen of olanzapine or aprepitant combined with 5-HT3RA and dexamethasone. The main evaluation indicators were the total protection (TP) rate in the acute phase (0-24 h), the delayed phase (25-120 h) and the overall phase (0-120 h).

Results: Univariate analysis was performed on genetic loci that reached H-W balance with TP. In the olanzapine group, increased TP in the acute phase was associated with HTR3A rs1176719 non-GG (P < 0.05) genotype etc. Increased TP in the delayed phase was associated with HTR3A rs1176719 non-GG (P < 0.05) genotype etc. In the aprepitant group, increased TP in the acute phase was associated with the MTHFR rs1801131 TT (P < 0.05) genotype etc. Increased TP in the delayed phase was associated with HTR3A rs1062613 CC (P < 0.05) genetype ect. Multivariate Logistic regression analysis showed that HTR3B rs7943062GG (P < 0.05) genotype etc. were correlated with increased TP in the delayed phase. MTHFR rs1801131TT genotype was associated with increased TP in the acute phase (P < 0.05) and delayed phase (P < 0.05).

Conclusion: This study found that gene polymorphisms, including HTR3B (rs1062613, rs1176719, rs2276303), HTR3B (rs45460698, rs7943062), HTR3C (rs6766410), ERCC1 (rs3212986), ERCC4 (rs744154) and MTHFR(rs1801131), may be independent prognostic factors for CINV.

Citing Articles

A prospective randomized controlled clinical trial investigating the efficacy of low-dose olanzapine in preventing nausea and vomiting associated with oxaliplatin-based and irinotecan-based chemotherapy.

Shen J, Zhao J, Jin G, Li H, Jiang Y, Wu Y J Cancer Res Clin Oncol. 2024; 150(5):283.

PMID: 38806870 PMC: 11133208. DOI: 10.1007/s00432-024-05712-7.

References
1.
Ward M, Kotasek D, McKinnon R . Investigation of HTR3C mutations for association with 5HT(3) receptor antagonist anti-emetic efficacy. Pharmacogenomics. 2008; 9(8):1027-33. DOI: 10.2217/14622416.9.8.1027. View

2.
De Rienzo F, Del Cadia M, Menziani M . A first step towards the understanding of the 5-HT3 receptor subunit heterogeneity from a computational point of view. Phys Chem Chem Phys. 2012; 14(36):12625-36. DOI: 10.1039/c2cp41028a. View

3.
Wheeler H, Gamazon E, Stark A, ODonnell P, Gorsic L, Huang R . Genome-wide meta-analysis identifies variants associated with platinating agent susceptibility across populations. Pharmacogenomics J. 2011; 13(1):35-43. PMC: 3370147. DOI: 10.1038/tpj.2011.38. View

4.
Kang G, Kim K, Shim H, Hwang J, Bae W, Chung I . Effect of the allelic variants of ABCB1, CYP2D6 and HTR3B on response of ramosetron to prevent chemotherapy-induced nausea and vomiting in Korean cancer patients. Asia Pac J Clin Oncol. 2016; 13(1):53-60. DOI: 10.1111/ajco.12575. View

5.
Krzywkowski K, Davies P, Feinberg-Zadek P, Brauner-Osborne H, Jensen A . High-frequency HTR3B variant associated with major depression dramatically augments the signaling of the human 5-HT3AB receptor. Proc Natl Acad Sci U S A. 2008; 105(2):722-7. PMC: 2206603. DOI: 10.1073/pnas.0708454105. View