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ATP-binding cassette (ABC) transporter expression and genetic heterogeneity have been implicated in response to anticancer therapy. This study characterized genetic variability of the ABCB1 (also known as MDR1), ABCC2 (MRP2) and ABCG2 (BCRP) genes, which are key players in the metabolism of many chemotherapeutic agents including those used in the treatment of lung cancer. We genotyped 53 polymorphisms in the candidate genes in genomic DNA samples of 171 cases of small cell lung carcinoma (SCLC) and 206 cases of non-small cell lung carcinoma (NSCLC), and studied their impact on early response to chemotherapy, progression-free survival and overall survival. SNP rs717620 in ABCC2 was moderately associated with a poor response to chemotherapy but strongly with shorter progression-free survival and overall survival in SCLC but not NSCLC patients, indicating that ABCC2 genetic variation is an important factor in SCLC survival after chemotherapy.

Introduction: We investigated the single-nucleotide polymorphism C-938A in the apoptotic gene BCL-2 to assess the potential impact as a genetic marker for response to chemotherapy and outcome prediction in small cell lung cancer (SCLC) patients. Such a marker might help optimize lung cancer treatment in a tailored approach. Methods: DNA derived from peripheral blood lymphocytes of 188 Caucasian SCLC patients treated at the Thoraxklinik Heidelberg was genotyped. Chemotherapy response, time to progression (TTP), and overall survival (OS) were evaluated using multivariable regression (unconditional logistic for response and Cox proportional hazard for TTP and OS) with odds ratios and hazard ratios (HRs) and their 95% confidence intervals (CIs) as quantitative outcome measures, respectively. Results: Small cell lung cancer patients carrying the BCL-2 -938CC genotype showed significantly worse TTP than patients carrying the BCL-2 -938AA genotype (HR = 1.86; 95% CI=1.10–3.13, p = 0.021). The same adverse effect was shown for OS (HR = 2.38; 95% CI=1.38–4.12, p = 0.002). Also, patients with limited disease (HR = 2.57; 95% CI=1.18–5.60, p = 0.017) showed worse OS with the BCL-2 -938CC genotype. Conclusion: BCL-2 -938CC genotype shows significantly worse outcome in small cell lung cancer patients. This genetic marker might particularly impact on treatment strategies using BCL-2 antisense approaches.