Efflux transporter variants as predictors of drug toxicity in lung cancer patients: systematic review and meta-analysis
| Autor: | Zoulikha M. Zaïr, Donald R. J. Singer |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Drug Oncology medicine.medical_specialty media_common.quotation_subject MEDLINE Antineoplastic Agents Pharmacology Cochrane Library 03 medical and health sciences 0302 clinical medicine Predictive Value of Tests Internal medicine Neoplasms Genetics Medicine Humans Lung cancer media_common biology business.industry Genetic Variation medicine.disease Multidrug Resistance-Associated Protein 2 030104 developmental biology Pharmacogenetics 030220 oncology & carcinogenesis Meta-analysis ABCA1 biology.protein Molecular Medicine Efflux business Carrier Proteins Adverse drug reaction |
| Zdroj: | Pharmacogenomics. 17(9) |
| ISSN: | 1744-8042 |
| Popis: | Chemotherapeutic drugs are underutilized in lung cancer management due in part to serious adverse drug reactions (ADRs). Aim: With studies revealing an association between interindividual patient ADR variation and efflux transporter variants, we carried out a meta-analysis and systemic review, in order to highlight current knowledge regarding the strength of association between efflux transporter SNPs variants and chemotherapeutic-drug induced ADRs. Materials & methods: Papers were sourced from MEDLINE, Cochrane Library, CINHL, EMBASE, Web of Knowledge, Scopus. The Cochrane Collaboration Risk of Bias Tool v13 was used to evaluate six types of bias domains for each of the publications reviewed. Results: Twenty-five publications comprising three randomised control trials, two retrospective case–controls and 20 clinical observation studies, totalling 3578 patients, were deemed eligible for review. Of the known efflux drug transporters, we report findings on the ABC members ABCB1, ABCC1, ABCC2, ABCG2, ABCA1, ABCC4 and ABCC5. Meta-analysis showed an decreased risk of irinotecan-induced neutropenia in patients expressing ABCB1 2677G>T/G (odds ratio [OR]: 0.24; 95% CI: 0.1–0.59; p = 0.002) but increased risk for ABCC2 3972T>T (OR: 1.67; 95% CI: 1.01–2.74; p = 0.04). ABCG2 34G>A was associated with a threefold increased risk of irinotecan-induced diarrhea (95% CI: 1.00–6.24; p = 0.05). Conclusion: The majority of studies have identified a role for variants in effluxdrug transporters in contributing to lung cancer treatment-associated ADRs. However, for implementation of use of these transporter genetic variants as prognostic markers for ADR risk, future studies must incorporate larger patient numbers. |
| Databáze: | OpenAIRE |
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