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

Szczegóły
Abstrakt

Tytuł:: Genetic variations in ABC transporter genes as a predictive biomarker for toxicity in North Indian lung cancer patients undergoing platinum-based doublet chemotherapy.
Autorzy:: Sharma P; Department of Biotechnology, Thapar Institute of Engineering & Technology, Patiala, Punjab, India.
Singh N; Department of Pulmonary Medicine, Post Graduate Institute of Medical Education & Research, Chandigarh, India.
Sharma S; Department of Biotechnology, Thapar Institute of Engineering & Technology, Patiala, Punjab, India.
Źródło:: Journal of biochemical and molecular toxicology [J Biochem Mol Toxicol] 2023 Mar; Vol. 37 (3), pp. e23269. Date of Electronic Publication: 2022 Dec 11.
Typ publikacji:: Journal Article
Język:: English
Imprint Name(s):: Original Publication: New York, NY : Wiley, c1998-
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
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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:: 20240105
DOI:: 10.1002/jbt.23269
PMID:: 36507589
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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.
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