Association of ABCC2 polymorphisms with platinum-based chemotherapy response and severe toxicity in non-small cell lung cancer patients

Platinum-based chemotherapy is the most common treatment for non-small cell lung cancer (NSCLC), and expression levels of drug metabolism and transport proteins are correlated with its efficacy and toxicity. In this study, we investigated the association of three putative functional polymorphisms of ABCC2 (C-24T, G1249A, and C3972T) with tumor response and occurrence of the grade 3 or 4 toxicity in 445 patients with stage III and IV NSCLC treated with platinum-based chemotherapy. We determined the genotypes of these three polymorphisms by the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MassArray) method. We found that the common homozygotes of -24C was associated with a better treatment response (adjusted odds ratios [ORs], 1.84; 95% confidence interval [CI], 1.05-3.23; P= 0.032). Furthermore, patients with 3972T had increased risk of severe thrombocytopenia toxicity (adjusted OR, 2.43; 95% CI, 1.06-5.56; P= 0.034); and in female subgroup analyses, this variant was associated with significantly increased risk of overall toxicity (adjusted OR, 2.63; 95% CI, 1.17-5.95; P= 0.02), particularly of hematologic toxicity (adjusted OR, 3.80; 95% CI, 1.62-8.87; P= 0.002). Moreover, -24T/3972T haplotype was also associated with significantly increased risk of hematologic toxicity. Our results suggested that C-24T variants had an effect on treatment response and that C3972T had an effect on severe toxicities among platinum-treated non-small cell lung cancer patients.