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

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...

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Main Authors: Chalirmporn Atasilp, Mohitosh Biswas, Pimonpan Jinda, Nutthan Nuntharadthanaphong, Jiratha Rachanakul, Yaowaluck Hongkaew, Natchaya Vanwong, Surasak Saokaew, Chonlaphat Sukasem
Other Authors: Ramathibodi Hospital
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Published: 2022
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Online Access:https://repository.li.mahidol.ac.th/handle/123456789/73260
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spelling th-mahidol.732602022-08-04T11:45:52Z Association of UGT1A1*6, UGT1A1*28, or ABCC2 c.3972C&gt;T genetic polymorphisms with irinotecan-induced toxicity in Asian cancer patients: Meta-analysis Chalirmporn Atasilp Mohitosh Biswas Pimonpan Jinda Nutthan Nuntharadthanaphong Jiratha Rachanakul Yaowaluck Hongkaew Natchaya Vanwong Surasak Saokaew Chonlaphat Sukasem Ramathibodi Hospital University of Phayao Chulalongkorn University Bumrungrad International Hospital Rajshahi University Faculty of Medicine Ramathibodi Hospital, Mahidol University Thammasat University Biochemistry, Genetics and Molecular Biology Neuroscience Pharmacology, Toxicology and Pharmaceutics 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. 2022-08-04T03:39:32Z 2022-08-04T03:39:32Z 2022-07-01 Article Clinical and Translational Science. Vol.15, No.7 (2022), 1613-1633 10.1111/cts.13277 17528062 17528054 2-s2.0-85130997723 https://repository.li.mahidol.ac.th/handle/123456789/73260 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85130997723&origin=inward
institution Mahidol University
building Mahidol University Library
continent Asia
country Thailand
Thailand
content_provider Mahidol University Library
collection Mahidol University Institutional Repository
topic Biochemistry, Genetics and Molecular Biology
Neuroscience
Pharmacology, Toxicology and Pharmaceutics
spellingShingle Biochemistry, Genetics and Molecular Biology
Neuroscience
Pharmacology, Toxicology and Pharmaceutics
Chalirmporn Atasilp
Mohitosh Biswas
Pimonpan Jinda
Nutthan Nuntharadthanaphong
Jiratha Rachanakul
Yaowaluck Hongkaew
Natchaya Vanwong
Surasak Saokaew
Chonlaphat Sukasem
Association of UGT1A1*6, UGT1A1*28, or ABCC2 c.3972C&gt;T genetic polymorphisms with irinotecan-induced toxicity in Asian cancer patients: Meta-analysis
description 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.
author2 Ramathibodi Hospital
author_facet Ramathibodi Hospital
Chalirmporn Atasilp
Mohitosh Biswas
Pimonpan Jinda
Nutthan Nuntharadthanaphong
Jiratha Rachanakul
Yaowaluck Hongkaew
Natchaya Vanwong
Surasak Saokaew
Chonlaphat Sukasem
format Article
author Chalirmporn Atasilp
Mohitosh Biswas
Pimonpan Jinda
Nutthan Nuntharadthanaphong
Jiratha Rachanakul
Yaowaluck Hongkaew
Natchaya Vanwong
Surasak Saokaew
Chonlaphat Sukasem
author_sort Chalirmporn Atasilp
title Association of UGT1A1*6, UGT1A1*28, or ABCC2 c.3972C&gt;T genetic polymorphisms with irinotecan-induced toxicity in Asian cancer patients: Meta-analysis
title_short Association of UGT1A1*6, UGT1A1*28, or ABCC2 c.3972C&gt;T genetic polymorphisms with irinotecan-induced toxicity in Asian cancer patients: Meta-analysis
title_full Association of UGT1A1*6, UGT1A1*28, or ABCC2 c.3972C&gt;T genetic polymorphisms with irinotecan-induced toxicity in Asian cancer patients: Meta-analysis
title_fullStr Association of UGT1A1*6, UGT1A1*28, or ABCC2 c.3972C&gt;T genetic polymorphisms with irinotecan-induced toxicity in Asian cancer patients: Meta-analysis
title_full_unstemmed Association of UGT1A1*6, UGT1A1*28, or ABCC2 c.3972C&gt;T genetic polymorphisms with irinotecan-induced toxicity in Asian cancer patients: Meta-analysis
title_sort association of ugt1a1*6, ugt1a1*28, or abcc2 c.3972c&gt;t genetic polymorphisms with irinotecan-induced toxicity in asian cancer patients: meta-analysis
publishDate 2022
url https://repository.li.mahidol.ac.th/handle/123456789/73260
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