Efflux transporter variants as predictors of drug toxicity in lung cancer patients: systematic review and meta-analysis

• Published in: Pharmacogenomics 2016-06, Vol.17 (9), p.1089-1112
• Main Authors: Zaïr, Zoulikha M, Singer, Donald RJ
• Format: Article
• Language: English
• Subjects: ABCA1 protein; adverse drug reaction; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - therapeutic use; ATP-binding protein; Bias; Cancer therapies; Carrier Proteins - genetics; Chemotherapy; Clinical trials; Diarrhea; Genes; Genetic diversity; Genetic Variation - genetics; Haplotypes; Humans; Irinotecan; Lung cancer; Meta-analysis; Neoplasms - drug therapy; Neoplasms - genetics; Neutropenia; Patients; Pharmacogenetics - methods; Predictive Value of Tests; Proteins; Single-nucleotide polymorphism; Systematic review; Toxicity
• ISSN: 1462-2416; 1744-8042
• DOI: 10.2217/pgs-2015-0006

Chemotherapeutic drugs are underutilized in lung cancer management due in part to serious adverse drug reactions (ADRs). 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. 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. 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 and . Meta-analysis showed an decreased risk of irinotecan-induced neutropenia in patients expressing 2677G>T/G (odds ratio [OR]: 0.24; 95% CI: 0.1-0.59; p = 0.002) but increased risk for 3972T>T (OR: 1.67; 95% CI: 1.01-2.74; p = 0.04). 34G>A was associated with a threefold increased risk of irinotecan-induced diarrhea (95% CI: 1.00-6.24; p = 0.05). 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.