Abstract
Abstract Purpose: We performed a case-control genome-wide association study (GWAS) to identify single nucleotide polymorphisms (SNPs) associated with severe diarrhea and neutropenia in patients treated with irinotecan for advanced non-small cell lung cancer (NSCLC). Patients and Methods: We performed a case-control GWAS using the Affymetrix 5.0 array set in 103 patients enrolled in two phase II studies of with irinotecan and cisplatin. A subsequent replication study was conducted to validate major GWAS findings in an independent series of 146 patients enrolled in another phase II study of irinotecan-based chemotherapy. Cases were defined as patients with grade 3 diarrhea (G3D) or grade 4 neutropenia (G4N) according to the National Cancer institute's Common Terminology Criteria for adverse events v3.0. Results: The GWAS included 11 G3D (control 90) and 24 G4N (control 77). The replication set included 13 G3D (control 133) and 21 G4N (control 125). GWAS identified 49 and 32 SNPs putatively associated with G3D and G4N, respectively. In the replication series, SNPs, rs1517114 (C8orf34), rs1661167 (FLJ41856), and rs2745761 (PLCB1) were confirmed for G3D, and rs11128347 (PDZRN3), rs11979430 and rs7779029 (SEMAC3) were confirmed for G4N. Conclusion: This GWAS screen along with subsequent validation indentified novels SNPs associated with irinotecan-related severe toxicities. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1866. doi:1538-7445.AM2012-1866
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