Open AccessAssociation of UGT1A1*6 , UGT1A1*28 , or ABCC2 c.3972C>T genetic polymorphisms with irinotecan‐induced toxicity in Asian cancer patients: Meta‐analysis
Author(s) -
Atasilp Chalirmporn,
Biswas Mohitosh,
Jinda Pimonpan,
Nuntharadthanaphong Nutthan,
Rachanakul Jiratha,
Hongkaew Yaowaluck,
Vanwong Natchaya,
Saokaew Surasak,
Sukasem Chonlaphat
Publication year - 2022
Publication title -
clinical and translational science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.303
H-Index - 44
eISSN - 1752-8062
pISSN - 1752-8054
DOI - 10.1111/cts.13277
Subject(s) - irinotecan , neutropenia , medicine , odds ratio , diarrhea , gastroenterology , cancer , toxicity , colorectal cancer
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.