Large-scale genetic study in East Asians identifies six new loci associated with colorectal cancer risk

Wei Zheng and colleagues report the results of a large-scale genome-wide association study of colorectal cancer in East Asians. They identify six new susceptibility loci, including variants near TCF7L2 and TGFB1 . Known genetic loci explain only a small proportion of the familial relative risk of colorectal cancer (CRC). We conducted a genome-wide association study of CRC in East Asians with 14,963 cases and 31,945 controls and identified 6 new loci associated with CRC risk ( P = 3.42 × 10 −8 to 9.22 × 10 −21 ) at 10q22.3, 10q25.2, 11q12.2, 12p13.31, 17p13.3 and 19q13.2. Two of these loci map to genes ( TCF7L2 and TGFB1 ) with established roles in colorectal tumorigenesis. Four other loci are located in or near genes involved in transcriptional regulation ( ZMIZ1 ), genome maintenance ( FEN1 ), fatty acid metabolism ( FADS1 and FADS2 ), cancer cell motility and metastasis ( CD9 ), and cell growth and differentiation ( NXN ). We also found suggestive evidence for three additional loci associated with CRC risk near genome-wide significance at 8q24.11, 10q21.1 and 10q24.2. Furthermore, we replicated 22 previously reported CRC-associated loci. Our study provides insights into the genetic basis of CRC and suggests the involvement of new biological pathways.