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Effect of drug metabolizing enzymes and transporters in Thai colorectal cancer patients treated with irinotecan-based chemotherapy.
- Source :
-
Scientific reports [Sci Rep] 2020 Aug 10; Vol. 10 (1), pp. 13486. Date of Electronic Publication: 2020 Aug 10. - Publication Year :
- 2020
-
Abstract
- Genetic polymorphisms in drug metabolizing enzymes and drug transporters may affect irinotecan toxicity. Although genetic polymorphisms have been shown to influence the irinotecan toxicity, data are limited in Thai population. Thus, the aim of this study was to assess the allele and genotype frequencies and the relationship between CYP3A4/5, DPYD, UGT1A1, ABCB1, and ABCC2 genetic variations and irinotecan-induced toxicity in Thai colorectal cancer patients. One hundred and thirty-two patients were genotyped, and the effect of genetic variations on irinotecan-induced toxicity was assessed in 66 patients who received irinotecan-based chemotherapy. Allele frequencies of ABCB1 c.1236C > T, ABCB1 c.3435C > T, ABCC2 c.3972C > T, ABCG2 c.421C > A, CYP3A4*1B, CYP3A4*18, CYP3A5*3, DPYD*5, UGT1A1*28, and UGT1A1*6 were 0.67, 0.43, 0.23, 0.27, 0.01, 0.02, 0.64, 0.19, 0.16, and 0.09, respectively. DPYD*2A and DPYD c.1774C > T variants were not detected in our study population. The ABCC2 c.3972C > T was significantly associated with grade 1-4 neutropenia (P < 0.012) at the first cycle. Patients carrying both UGT1A1*28 and *6 were significantly associated with severe neutropenia at the first (P < 0.001) and second (P = 0.017) cycles. In addition, patients carrying UG1A1*28 and *6 had significantly lower absolute neutrophil count (ANC) nadir at first (P < 0.001) and second (P = 0.001) cycles. This finding suggests that UGT1A1*28, *6, and ABCC2 c.3972C > T might be an important predictor for irinotecan-induced severe neutropenia.
- Subjects :
- ATP Binding Cassette Transporter, Subfamily B, Member 1 genetics
ATP-Binding Cassette Transporters genetics
Adult
Aged
Alleles
Cytochrome P-450 CYP3A genetics
Female
Gene Frequency genetics
Genetic Variation genetics
Genotype
Glucuronosyltransferase genetics
Humans
Irinotecan metabolism
Irinotecan therapeutic use
Male
Membrane Transport Proteins genetics
Middle Aged
Multidrug Resistance-Associated Protein 2
Multidrug Resistance-Associated Proteins genetics
Neutropenia chemically induced
Polymorphism, Genetic genetics
Thailand epidemiology
Colorectal Neoplasms drug therapy
Colorectal Neoplasms genetics
Irinotecan pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 10
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 32778670
- Full Text :
- https://doi.org/10.1038/s41598-020-70351-0