Association of UGT1A1*6, UGT1A1*28, or ABCC2 c.3972C>T genetic polymorphisms with irinotecan‐induced toxicity in Asian cancer patients: Meta‐analysis

• Main Authors: Chalirmporn Atasilp (Author), Mohitosh Biswas (Author), Pimonpan Jinda (Author), Nutthan Nuntharadthanaphong (Author), Jiratha Rachanakul (Author), Yaowaluck Hongkaew (Author), Natchaya Vanwong (Author), Surasak Saokaew (Author), Chonlaphat Sukasem (Author)
• Format: Book
• Published: Wiley, 2022-07-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 1752-8062; 1752-8054; 10.1111/cts.13277
• Keywords: Therapeutics. Pharmacology; RM1-950; Public aspects of medicine; RA1-1270
• Source: Clinical and Translational Science, Vol 15, Iss 7, Pp 1613-1633 (2022)

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.