genetic polymorphisms with irinotecan induced toxicity in Asian cancer patients: Meta-analysis
Chalirmporn Atasilp1, Mohitosh Biswas2,3,4, Pimonpan Jinda2,3, Nutthan Nuntharadthanaphong2,3, Jiratha Rachanakul2,3, Yaowaluck Hongkaew5, Natchaya Vanwong6, Surasak Saokaew7,8,9, Chonlaphat Sukasem2,3,10*
1Chulabhorn International College of Medicine, Thammasat University, Pathum Thani, Thailand
2Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
3Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, Thailand
4Department of Pharmacy, University of Rajshahi, Rajshahi, 6205, Bangladesh
5Advance Research and Development Laboratory, Bumrungrad International Hospital, Bangkok, Thailand
6Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, Thailand.
7Division of Pharmacy Practice, Department of Pharmaceutical Care, School of Pharmaceutical Sciences, University of Phayao, Phayao, Thailand.8Center of Health Outcomes Research and Therapeutic Safety (Cohorts), School of Pharmaceutical Sciences, University of Phayao, Phayao, Thailand.9Unit of Excellence on Clinical Outcomes Research and IntegratioN (UNICORN), School of Pharmaceutical Sciences, University of Phayao, Phayao, Thailand.10Pharmacogenomics and Precision Medicine, The Preventive Genomics & Family Check-up Services Center, Bumrungrad International Hospital, Bangkok, Thailand
* Correspondence: chonlaphat.suk@mahidol.ac.th; Tel.: (+66)-2-200-4330
Abstract: Background: 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. It was aimed to assess the aggregated risk of neutropenia or diarrhea in Asian cancer patients taking irinotecan and inherited UGT1A1*6 , UGT1A1*28 orABCC2 c.3972C>T genetic variants. Methods: Literature was searched in PubMed for eligible studies. Odds ratios (ORs) were measured using RevMan software whereP -values<0.05 were statistically significant. Results: Patients 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 carried 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 with heterozygous variants. However, patients carried ABCC2c.3972C>T genetic variant were not significantly associated with neutropenia (OR 1.67; 95% CI 0.98–2.84; P =0.06) but reduced diarrhea singnificantly (OR 0.31; 95% CI 0.11–0.81;P =0.02). Conclusions: Both UGT1A1*6 and UGT1A1*28genetic variants should screen in Asian cancer patients to reduce substantially irinotecan induced severe toxicities.
Keywords:Irinotecan, UGT1A1, ABCC2,genetic polymorphisms, toxicity