Abstract
5567 Background: This study evaluated the relationship between known functional variants in three ATP-binding cassette (ABC) transporter genes (ABCB1 [MDR1], ABCC2 [MRP2], and ABCG2 [BCRP]) and clinical outcomes in epithelial ovarian cancer (EOC). These genes induce resistance to multiple anticancer drugs and some polymorphisms appear to affect expression, stability or activity of these transporters. Methods: Genotypes for common polymorphisms in ABCB1 (G2677T/A, A893S/T -RS2032582 and C3435T, synonymous-RS1045642), ABCC2 (G1249A, V417I-RS2273697), and ABCG2 (C421A, Q141K-RS2231138) were determined in normal blood DNA from 385 women with optimal stage III ECO who participated in a randomized phase III trial (GOG 172 or 182) and were treated with intravenous or intraperitoneal platinum+paclitaxel. Associations between polymorphisms and progression-free survival (PFS) and overall survival (OS) were examined using logrank test and adjusted Cox regression analysis. Results: The genotype distribution for the C421A polymorphism in ABCG2 was 80.7%, 18.5% and 0.8% for CC, CA and AA, respectively. Median time to disease progression or death for the CA+AA versus (vs.) CC genotype in ABCG2 was 30.3 vs. 18.1 months (p = 0.023), or 69.8 vs. 51.6 months (p = 0.172), respectively. After adjusting for clinical covariates, women with the CA+AA vs. CC genotype in ABCG2 had a significant reduction in the risk of disease progression (hazard ratio [HR] = 0.67, 95% confidence interval [CI] = 0.49–0.91, p = 0.01) but not death (HR = 0.77, 95% CI = 0.56–1.08, p = 0.125). The results were consistent across treatments. Adjusted Cox modeling demonstrated that polymorphisms in ABCB1 (G2677T/A or C3435T) and ABCC2 (G1249A) were not associated with PFS or OS. Conclusions: The ABCG2 C421A polymorphism, but not the ABCB1 G2677T/A, ABCB1 C3435T, or ABCC2 G1249A polymorphism, appears to be an independent prognostic factor for disease progression in optimal stage III EOC treated with platinum + paclitaxel therapy. No significant financial relationships to disclose.
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