Journal Article

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

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

2014

Overview

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.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 45/22 / 45/43 / 631/208/205/2138 / 692/699/1503/1504/1885 / Agriculture / Animal Genetics and Genomics / Asian People - genetics / Biomedicine / Cancer Research / Case-Control Studies / China / Chromosome Mapping / Colorectal cancer / Colorectal carcinoma / Colorectal Neoplasms - ethnology / Colorectal Neoplasms - genetics / Computational Biology / Delta-5 Fatty Acid Desaturase / Female / Gene Expression Profiling / Gene Function / Genes / Genetic aspects / Genetic Loci / Genetic Predisposition to Disease / Genetic research / Genetic susceptibility / Genetic Variation / Genome-Wide Association Study / Genotype / Health risks / Human Genetics / Humans / Identification and classification / Japan / Male / Medical research / Neoplasm Metastasis / Polymorphism, Single Nucleotide / Quantitative trait loci / Republic of Korea / Risk / Risk factors / Studies