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