Association of UGT1A1*6, UGT1A1*28, or ABCC2 c.3972C>T genetic polymorphisms with irinotecan-induced toxicity in Asian cancer patients: Meta-analysis.
Clin Transl Sci
; 15(7): 1613-1633, 2022 07.
Article
em En
| MEDLINE
| ID: mdl-35506159
ABSTRACT
Effects of UGT1A1*6 and UGT1A1*28 genetic polymorphisms on irinotecan-induced severe toxicities in Asian cancer patients are inconclusive. Also, ABCC2 c.3972C>T may affect toxicity of irinotecan. The aim was to assess the aggregated risk of neutropenia or diarrhea in Asian cancer patients taking irinotecan and inherited UGT1A1*6, UGT1A1*28, or ABCC2 c.3972C>T genetic variants. A PubMed literature search for eligible studies was conducted. Odds ratios (ORs) were measured using RevMan software where p values <0.05 were statistically significant. Patients that inherited both UGT1A1*6 and UGT1A1*28 genetic variants (heterozygous UGT1A1*1/*6 + *1/*28 and homozygous UGT1A1*6/*6 + *28/*28) were significantly associated with increased risk of neutropenia and diarrhea compared to patients with UGT1A1*1/*1 (neutropenia OR 2.89; 95% CI 1.97-4.23; p < 0.00001; diarrhea OR 2.26; 95% CI 1.71-2.99; p < 0.00001). Patients carrying homozygous variants had much stronger effects in developing toxicities (neutropenia OR 6.23; 95% CI 3.11-12.47; p < 0.00001; diarrhea OR 3.21; 95% CI 2.13-4.85; p < 0.00001) than those with heterozygous variants. However, patients carrying the ABCC2 c.3972C>T genetic variant were not significantly associated with neutropenia (OR 1.67; 95% CI 0.98-2.84; p = 0.06) and were significantly associated with a reduction in irinotecan-induced diarrhea (OR 0.31; 95% CI 0.11-0.81; p = 0.02). Asian cancer patients should undergo screening for both UGT1A1*6 and UGT1A1*28 genetic variants to reduce substantially irinotecan-induced severe toxicities.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
2_ODS3
/
3_ND
Base de dados:
MEDLINE
Assunto principal:
Glucuronosiltransferase
/
Diarreia
/
Inibidores da Topoisomerase I
/
Irinotecano
/
Neoplasias
/
Neutropenia
/
Antineoplásicos Fitogênicos
Tipo de estudo:
Risk_factors_studies
/
Systematic_reviews
Limite:
Humans
Idioma:
En
Revista:
Clin Transl Sci
Ano de publicação:
2022
Tipo de documento:
Article