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

Ben Zhang, Wei Hua Jia, Koichi Matsuda, Sun Seog Kweon, Keitaro Matsuo, Yong Bing Xiang, Aesun Shin, Sun Ha Jee, Dong Hyun Kim, Qiuyin Cai, Jirong Long, Jiajun Shi, Wanqing Wen, Gong Yang, Yanfeng Zhang, Chun Li, Bingshan Li, Yan Guo, Zefang Ren, Bu Tian JiZhi Zhong Pan, Atsushi Takahashi, Min Ho Shin, Fumihiko Matsuda, Yu Tang Gao, Jae Hwan Oh, Soriul Kim, Yoon Ok Ahn, Andrew T. Chan, Jenny Chang-Claude, Martha L. Slattery, Stephen B. Gruber, Fredrick R. Schumacher, Stephanie L. Stenzel, Graham Casey, Hyeong Rok Kim, Jin Young Jeong, Ji Won Park, Hong Lan Li, Satoyo Hosono, Sang Hee Cho, Michiaki Kubo, Xiao Ou Shu, Yi Xin Zeng, Wei Zheng

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Abstract

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 â ̂'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.

Original languageEnglish
Pages (from-to)533-542
Number of pages10
JournalNature Genetics
Volume46
Issue number6
DOIs
Publication statusPublished - 06-2014

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All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Zhang, B., Jia, W. H., Matsuda, K., Kweon, S. S., Matsuo, K., Xiang, Y. B., Shin, A., Jee, S. H., Kim, D. H., Cai, Q., Long, J., Shi, J., Wen, W., Yang, G., Zhang, Y., Li, C., Li, B., Guo, Y., Ren, Z., ... Zheng, W. (2014). Large-scale genetic study in east Asians identifies six new loci associated with colorectal cancer risk. Nature Genetics, 46(6), 533-542. https://doi.org/10.1038/ng.2985