Gong Yang
Faculty Member
Last active: 4/27/2017

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

Zhang B, Jia WH, Matsuda K, Kweon SS, Matsuo K, Xiang YB, Shin A, Jee SH, Kim DH, Cai Q, Long J, Shi J, Wen W, Yang G, Zhang Y, Li C, Li B, Guo Y, Ren Z, Ji BT, Pan ZZ, Takahashi A, Shin MH, Matsuda F, Gao YT, Oh JH, Kim S, Ahn YO, Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), Chan AT, Chang-Claude J, Slattery ML, Colorectal Transdisciplinary (CORECT) Study, Gruber SB, Schumacher FR, Stenzel SL, Colon Cancer Family Registry (CCFR), Casey G, Kim HR, Jeong JY, Park JW, Li HL, Hosono S, Cho SH, Kubo M, Shu XO, Zeng YX, Zheng W
Nat Genet. 2014 46 (6): 533-42

PMID: 24836286 · PMCID: PMC4068797 · DOI:10.1038/ng.2985

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.

MeSH Terms (20)

Asian Continental Ancestry Group Case-Control Studies China Chromosome Mapping Colorectal Neoplasms Computational Biology Female Gene Expression Profiling Genetic Loci Genetic Predisposition to Disease Genetic Variation Genome-Wide Association Study Genotype Humans Japan Male Neoplasm Metastasis Polymorphism, Single Nucleotide Republic of Korea Risk

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