A randomized trial evaluating the association between related gene polymorphism and nausea and vomiting induced by cisplatin multi-day chemotherapy

BMC Med Genomics. 2023 Nov 3;16(1):276. doi: 10.1186/s12920-023-01719-0.

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.

Keywords: CINV; Cisplatin; Gene Polymorphism; Multi-day chemotherapy.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiemetics / therapeutic use
  • Antineoplastic Agents* / adverse effects
  • Aprepitant / therapeutic use
  • Cisplatin* / adverse effects
  • Humans
  • Nausea / chemically induced
  • Nausea / drug therapy
  • Nausea / genetics
  • Olanzapine / therapeutic use
  • Polymorphism, Genetic
  • Vomiting / chemically induced
  • Vomiting / drug therapy
  • Vomiting / genetics

Substances

  • Antiemetics
  • Antineoplastic Agents
  • Aprepitant
  • Cisplatin
  • Olanzapine

Associated data

  • ChiCTR/ChiCTR20000368269