Abstract 1140: Novel single-nucleotide polymorphism markers predictive of pathologic response to preoperative chemoradiotherapy in rectal cancer patients.

Abstract

Abstract Purpose: Studies aimed at predicting individual responsiveness to preoperative chemoradiotherapy (CRT) are urgently needed, especially considering the risks associated with poorly responsive patients, i.e., delay of curative surgery, immune suppression, and adverse effects. Methods and Materials: A three-step strategy for the determination of CRT sensitivity is proposed that includes: 1) screening of a human genome-wide single-nucleotide polymorphism (SNP) array correlated with histopathological tumor regression grade (TRG), 2) clinical association analysis in 113 patients treated with preoperative CRT, and 3) a cell-based functional assay for biological validation. Genome-wide screening identified nine SNPs associated with preoperative CRT responses. Results: Genome-wide screening identified nine SNPs associated with preoperative CRT responses. The patients carrying the reference allele (C) of the SNP CORO2A rs1985859 exhibited greater positive responses (TRG 1-3) than those with the substitution allele (T) (P=0.01). Down-regulation of CORO2A was associated with significantly reduced early apoptosis in RKO and COLO320DM colorectal cancer cells by 27% (P=0.048) and 39% (P=0.023), respectively, as determined by flow cytometry. Although a specific genotype associated with radiosensitivity was not detected in the clinical association analysis, down-regulation of FAM101A significantly increased the viability of RKO and COLO320DM cells by 25% (P=0.01) and 23% (P=0.023), respectively in the MTT assay. Conclusion: CRT-sensitive SNP markers were identified using a novel three-step process. The candidate marker CORO2A rs1985859 and the putative marker FAM101A rs7955740 may improve the prediction of radiosensitivity to preoperative CRT, although further validation is needed in large cohorts. Citation Format: Jin Cheon Kim, Seon Ae Roh, Dong Hyung Cho, Eun Young Choi, Ye Jin Ha, Tae Won Kim, Jong Hoon Kim, Tae Wook Kang, Seon Young Kim, Yong Sung Kim. Novel single-nucleotide polymorphism markers predictive of pathologic response to preoperative chemoradiotherapy in rectal cancer patients. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1140. doi:10.1158/1538-7445.AM2013-1140