GENOME-WIDE SEARCH FOR NOVEL CANCER GENES IN SPORADIC AND FAMILIAL COLORECTAL CANCERS

Abstract

Colorectal cancer (CRC) is one of the most frequent cancer incident worldwide. Only six out of the fourteen Caucasian-identified SNPs interrogated showed evidence of association with CRC risk in Singapore Chinese (SCH). Genome-wide association study (GWAS) did not identify new variant in SCH, however, genotype data were contributed to a CRC GWAS and identified a new SMAD7 risk variant in East Asians. Imputed data of rs5275 was found to be significantly associated with CRC risk in female. A rare copy number variant (CNV) at chromosome 14q11 encompassing CHD8, and common CNVs at 3q13.12 encompassing CD47 and 12p12.3 consisting RERG and ARHGDIB were significantly associated with sporadic CRC in SCH. CHD8 is a chromatin modifier in Wnt signalling pathway while RERG and ARHGDIB are linked to proliferation and tumorigenic potential and metastasis. Result also implied that a 19q13 genomic deletion caused chromatin disruption and perturbed expressions of CYP2A7, MIA and MIA-RAB4B IncRNA in familial CRC patients.