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ATP-binding cassette (ABC) transporters are expressed in various human tissues and play a vital role in the efflux of various chemotherapeutic drugs. The current study has assessed genetic variants of ABCB1, ABCC1, ABCC2, and ABCG2 genes in 407 lung cancer patients undergoing platinum-based doublet chemotherapy. The association of ABCB1 (C 1236 T, C 3435 T, and G 2677 T/A), ABCC1 (G 3173 A and G 2168 A),ABCC2 (G 4544 A), and ABCG2 (C 421 A) polymorphisms with chemotherapy-induced adverse events were assessed, and statistical analysis was conducted. Our data showed that patients harboring heterozygous (GA) genotype for ABCC1 G 3173 A had an increased risk of developing leukopenia (odds ratio [OR] = 1.88, p = 0.04) and anemia (adjusted odds ratio [AOR] = 2.70, p = 0.03). For ABCC2 G 4544 A polymorphism, patients harboring one copy of the mutant (GA) allele showed an increased risk of developing anemia (OR = 4.24, p = 0.03). After adjusting with various confounding factors, the heterozygous (GA) genotype showed a 5.63-fold increased risk of developing anemia (AOR = 5.63, p = 0.03). The ABCB1 G 2677 A (OR = 0.37, p = 0.008) and ABCC1 G 3173 A (OR = 0.54, p = 0.04) polymorphism showed a lower incidence of developing nephrotoxicity. In ABCG2 C 421 A polymorphism, patients harboring heterozygous (CA) genotype had a lower incidence of having diarrhea (OR = 0.25, p = 0.04). An increased risk of having diarrhea was observed in the heterozygous genotype (GA) for ABCC1 G 3173 A polymorphism (AOR = 2.78, p = 0.04). An increased risk of liver injury was found in the patients carrying heterozygous genotype of the ABCC1 G 3173 A (OR = 2.06, p = 0.02) and ABCB1 C 1236 T (OR = 1.85, p = 0.01). This study demonstrates the role of polymorphic variations in ABCB1, ABCC1, ABCC2, and ABCG2 in predicting hematological, nephrotoxicity, gastrointestinal, and hepatotoxicity.

Titel:	Genetic variations in ABC transporter genes as a predictive biomarker for toxicity in North Indian lung cancer patients undergoing platinum-based doublet chemotherapy.
Autor/in / Beteiligte Person:	Sharma, P ; Singh, N ; Sharma, S
Link:	Full Text Finder (Volltext)
Zeitschrift:	Journal of biochemical and molecular toxicology, Jg. 37 (2023-03-01), Heft 3, S. e23269
Veröffentlichung:	New York, NY : Wiley, c1998-, 2023
Medientyp:	academicJournal
ISSN:	1099-0461 (electronic)
DOI:	10.1002/jbt.23269
Schlagwort:	Adult Aged Aged, 80 and over Female Humans Male Middle Aged Anemia chemically induced Anemia genetics Carcinoma, Non-Small-Cell Lung drug therapy Carcinoma, Non-Small-Cell Lung genetics Carcinoma, Non-Small-Cell Lung pathology Chemical and Drug Induced Liver Injury etiology Chemical and Drug Induced Liver Injury genetics Diarrhea chemically induced Diarrhea genetics Docetaxel administration & dosage Docetaxel adverse effects Etoposide administration & dosage Etoposide adverse effects Gefitinib administration & dosage Gefitinib adverse effects Gemcitabine administration & dosage Gemcitabine adverse effects Genotype India Irinotecan administration & dosage Irinotecan adverse effects Kidney Diseases chemically induced Kidney Diseases genetics Leukopenia chemically induced Leukopenia genetics Paclitaxel administration & dosage Paclitaxel adverse effects Pemetrexed administration & dosage Pemetrexed adverse effects Polymorphism, Genetic Small Cell Lung Carcinoma drug therapy Small Cell Lung Carcinoma genetics Small Cell Lung Carcinoma pathology Antineoplastic Combined Chemotherapy Protocols adverse effects Antineoplastic Combined Chemotherapy Protocols therapeutic use ATP-Binding Cassette Transporters genetics Carboplatin administration & dosage Carboplatin adverse effects Cisplatin administration & dosage Cisplatin adverse effects Lung Neoplasms drug therapy Lung Neoplasms genetics Lung Neoplasms pathology South Asian People genetics
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [J Biochem Mol Toxicol] 2023 Mar; Vol. 37 (3), pp. e23269. <i>Date of Electronic Publication: </i>2022 Dec 11. MeSH Terms: Antineoplastic Combined Chemotherapy Protocols* / adverse effects ; Antineoplastic Combined Chemotherapy Protocols* / therapeutic use ; ATP-Binding Cassette Transporters* / genetics ; Carboplatin* / administration & dosage ; Carboplatin* / adverse effects ; Cisplatin* / administration & dosage ; Cisplatin* / adverse effects ; Lung Neoplasms* / drug therapy ; Lung Neoplasms* / genetics ; Lung Neoplasms* / pathology ; South Asian People* / genetics ; Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Anemia / chemically induced ; Anemia / genetics ; Carcinoma, Non-Small-Cell Lung / drug therapy ; Carcinoma, Non-Small-Cell Lung / genetics ; Carcinoma, Non-Small-Cell Lung / pathology ; Chemical and Drug Induced Liver Injury / etiology ; Chemical and Drug Induced Liver Injury / genetics ; Diarrhea / chemically induced ; Diarrhea / genetics ; Docetaxel / administration & dosage ; Docetaxel / adverse effects ; Etoposide / administration & dosage ; Etoposide / adverse effects ; Gefitinib / administration & dosage ; Gefitinib / adverse effects ; Gemcitabine / administration & dosage ; Gemcitabine / adverse effects ; Genotype ; India ; Irinotecan / administration & dosage ; Irinotecan / adverse effects ; Kidney Diseases / chemically induced ; Kidney Diseases / genetics ; Leukopenia / chemically induced ; Leukopenia / genetics ; Paclitaxel / administration & dosage ; Paclitaxel / adverse effects ; Pemetrexed / administration & dosage ; Pemetrexed / adverse effects ; Polymorphism, Genetic ; Small Cell Lung Carcinoma / drug therapy ; Small Cell Lung Carcinoma / genetics ; Small Cell Lung Carcinoma / pathology References: R. 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Rec. 2010, 293(7), 1167. Contributed Indexing: Keywords: ABC transporter; lung cancer; polymorphism; risk; toxicity Substance Nomenclature: 0 (ABCB1 protein, human) ; 0 (ABCC2 protein, human) ; 0 (ABCG2 protein, human) ; 0 (ATP-Binding Cassette Transporters) ; BG3F62OND5 (Carboplatin) ; Q20Q21Q62J (Cisplatin) ; 15H5577CQD (Docetaxel) ; 6PLQ3CP4P3 (Etoposide) ; S65743JHBS (Gefitinib) ; 0 (Gemcitabine) ; 7673326042 (Irinotecan) ; Y49M64GZ4Q (multidrug resistance-associated protein 1) ; P88XT4IS4D (Paclitaxel) ; 04Q9AIZ7NO (Pemetrexed) Entry Date(s): Date Created: 20221212 Date Completed: 20230411 Latest Revision: 20230411 Update Code: 20240513

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Genetic variations in ABC transporter genes as a predictive biomarker for toxicity in North Indian lung cancer patients undergoing platinum-based doublet chemotherapy.