GWAS-identified colorectal cancer susceptibility locus associates with disease prognosis Jinliang Xing a , Ronald E. Myers b , Xianli He c , Falin Qu c , Feng Zhou c , Xi Ma a , Terry Hyslop d , Guoqiang Bao c , Shaogui Wan b , Hushan Yang b, * , Zhinan Chen a, * a State Key Laboratory of Cancer Biology, Cell Engineering Research Centre, Department of Cell Biology, Fourth Military Medical University, Xi’an 710032, China b Division of Population Science, Department of Medical Oncology, Thomas Jefferson University, Philadelphia, PA 19107, USA c Tangdu Hospital, Department of General Surgery, Fourth Military Medical University, Xi’an 710032, China d Division of Biostatistics, Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA 19107, USA ARTICLE INFO Article history: Received 9 October 2010 Received in revised form 2 February 2011 Accepted 3 February 2011 Available online 12 March 2011 Keywords: Single nucleotide polymorphism Colorectal cancer Prognosis ABSTRACT Purpose: Extensive evidence has suggested that risk factors of cancer development may also modulate cancer clinical outcome. Recent genome-wide association (GWA) studies identified several single nucleotide polymorphisms (SNPs) predisposing to colorectal can- cer (CRC). Given the pivotal importance of these variants in CRC, we sought to evaluate their associations with clinical outcomes of the disease. Experimental Design: In a well-characterised cohort including 380 Chinese CRC patients, we genotyped seven SNPs identified in previous multi-stage GWA studies and analysed their associations with patient recurrence and survival. Results: One SNP on chromosome 15q13, rs4779584 was associated with reduced risk of death with a hazard ratio (HR) of 0.33 (95% confidence interval [CI] 0.15–0.72, P = 0.007). Another SNP in a gene-desert region on chromosome 10p14, rs10795668, was associated with a reduced risk of recurrence with an HR of 0.55 (95% CI 0.30–1.00, P = 0.05). In a strat- ified analysis, this association was only evident in patients receiving chemotherapy (HR = 0.32, 95% CI 0.14–0.78, P = 0.01, log rank P = 0.004), but not in those without chemo- therapy (HR = 1.08, 95% CI 0.43–2.73, P = 0.87, log rank P = 0.66). Moreover, we found that the effects of chemotherapy on CRC recurrence was only evident in patients with the variant-containing genotypes (HR = 0.35, 95% CI 0.13–0.94, P = 0.04) but not in those with the wild-type genotype of rs10795668. Further analyses indicated a borderline significant interaction effect (P interaction = 0.05) between rs10795668 and chemotherapy on patient recurrence. Conclusions: Our data suggested that rs10795668, a CRC susceptibility variant identified by GWA studies, might be used as a biomarker to identify CRC patients with high risk of recurrence after chemotherapy. Ó 2011 Elsevier Ltd. All rights reserved. 0959-8049/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.ejca.2011.02.004 * Corresponding authors: Addresses: Department of Cell Biology, Cell Engineering Research Centre, State Key Laboratory of Cancer Biology, Fourth Military Medical University, 17 West Changle Street, Xi’an 710032, China. Tel.: +86 29 84774547; fax: +86 29 83293906 (Z. Chen), Division of Population Science, Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA. Tel.: +1 215 5036521; fax: +1 267 3360247 (H. Yang). E-mail addresses: hushan.yang@jefferson.edu (H. Yang), znchen@fmmu.edu.cn (Z. Chen). EUROPEAN JOURNAL OF CANCER 47 (2011) 1699 – 1707 available at www.sciencedirect.com journal homepage: www.ejconline.com