Abstract 2189: A rare copy number variant at chromosome 14q11 was associated with sporadic colorectal cancer risk in Singapore Chinese

Abstract

Abstract Colorectal cancer (CRC) is one of the most frequent cancers and leading cause of cancer mortality in the developed world. Twin study has attributed about 35% of the etiology of sporadic CRC to genes. Structural variations in the human genome have recently been associated with complex neurological diseases. Their role in CRC, however, is unclear. We performed genome-wide association study (GWAS) on 2,000 ethnicity-, age-, and gender-matched Singapore Chinese CRC patients (aged 50 or more and with no dominant family history of CRC) and healthy controls. Genome-wide genotyping was performed using Affymetrix SNP 6 platform, and rare copy number variants (CNV) were interrogated in 1830 samples that passed the quality assurance tests. A 400 kb region at chromosome 14q11 was identified to be significantly associated (-log10 p-value = 11) with sporadic CRC risk. A chromatin modifier implicated in the β-catenin/Wnt signalling pathway is one of the candidate genes found in the region. Primers unique for this gene applied to an optimal real-time copy number assay verified the CNV region in an independent replication panel comprising another 1,000 sporadic CRC cases. About 6% of the cases exhibit copy number alterations at this region compared to 1% in the healthy controls. A second gene, a small guanosine triphosphatase (GTPase) involved in protein trafficking and preferentially up-regulated in colonic tumors , was shown by long-range polymerase chain reaction to have more structural variations in the cases compared to the controls. Furthermore, expression of the H1 binding domain of the chromatin modifier was positively correlated to the expressions of Cyclin D1 and C-myc. The data suggest that the rare CNV in 14q11 was dynamically associated with the activation of genes implicated in sporadic CRC in the Singapore Chinese. Citation Format: Peh Yean Cheah, Lai Fun Thean, Yik-Ying Teo, Woon-Puay Koh, Jian-Min Yuan, Poh Koon Koh, Min Hoe Chew, Choong Leong Tang. A rare copy number variant at chromosome 14q11 was associated with sporadic colorectal cancer risk in Singapore Chinese. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2189. doi:10.1158/1538-7445.AM2014-2189