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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Colorectal Neoplasms
Genome
Genetic Loci
Genome-Wide Association Study
Genes
Cell Movement
Cell Differentiation
Carcinogenesis
Fatty Acids
Maintenance
Neoplasm Metastasis
Growth
Neoplasms

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Zhang, B., Jia, W. H., Matsuda, K., Kweon, S. S., Matsuo, K., Xiang, Y. B., ... 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
Zhang, Ben ; Jia, Wei Hua ; Matsuda, Koichi ; Kweon, Sun Seog ; Matsuo, Keitaro ; Xiang, Yong Bing ; Shin, Aesun ; Jee, Sun Ha ; Kim, Dong Hyun ; Cai, Qiuyin ; Long, Jirong ; Shi, Jiajun ; Wen, Wanqing ; Yang, Gong ; Zhang, Yanfeng ; Li, Chun ; Li, Bingshan ; Guo, Yan ; Ren, Zefang ; Ji, Bu Tian ; Pan, Zhi Zhong ; Takahashi, Atsushi ; Shin, Min Ho ; Matsuda, Fumihiko ; Gao, Yu Tang ; Oh, Jae Hwan ; Kim, Soriul ; Ahn, Yoon Ok ; Chan, Andrew T. ; Chang-Claude, Jenny ; Slattery, Martha L. ; Gruber, Stephen B. ; Schumacher, Fredrick R. ; Stenzel, Stephanie L. ; Casey, Graham ; Kim, Hyeong Rok ; Jeong, Jin Young ; Park, Ji Won ; Li, Hong Lan ; Hosono, Satoyo ; Cho, Sang Hee ; Kubo, Michiaki ; Shu, Xiao Ou ; Zeng, Yi Xin ; Zheng, Wei. / Large-scale genetic study in east Asians identifies six new loci associated with colorectal cancer risk. In: Nature Genetics. 2014 ; Vol. 46, No. 6. pp. 533-542.
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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 {\^a} ̂'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.",
author = "Ben Zhang and Jia, {Wei Hua} and Koichi Matsuda and Kweon, {Sun Seog} and Keitaro Matsuo and Xiang, {Yong Bing} and Aesun Shin and Jee, {Sun Ha} and Kim, {Dong Hyun} and Qiuyin Cai and Jirong Long and Jiajun Shi and Wanqing Wen and Gong Yang and Yanfeng Zhang and Chun Li and Bingshan Li and Yan Guo and Zefang Ren and Ji, {Bu Tian} and Pan, {Zhi Zhong} and Atsushi Takahashi and Shin, {Min Ho} and Fumihiko Matsuda and Gao, {Yu Tang} and Oh, {Jae Hwan} and Soriul Kim and Ahn, {Yoon Ok} and Chan, {Andrew T.} and Jenny Chang-Claude and Slattery, {Martha L.} and Gruber, {Stephen B.} and Schumacher, {Fredrick R.} and Stenzel, {Stephanie L.} and Graham Casey and Kim, {Hyeong Rok} and Jeong, {Jin Young} and Park, {Ji Won} and Li, {Hong Lan} and Satoyo Hosono and Cho, {Sang Hee} and Michiaki Kubo and Shu, {Xiao Ou} and Zeng, {Yi Xin} and Wei Zheng",
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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, Chan, AT, Chang-Claude, J, Slattery, ML, Gruber, SB, Schumacher, FR, Stenzel, SL, Casey, G, Kim, HR, Jeong, JY, Park, JW, Li, HL, Hosono, S, Cho, SH, Kubo, M, Shu, XO, Zeng, YX & Zheng, W 2014, 'Large-scale genetic study in east Asians identifies six new loci associated with colorectal cancer risk', Nature Genetics, vol. 46, no. 6, pp. 533-542. https://doi.org/10.1038/ng.2985

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

In: Nature Genetics, Vol. 46, No. 6, 06.2014, p. 533-542.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Large-scale genetic study in east Asians identifies six new loci associated with colorectal cancer risk

AU - Zhang, Ben

AU - Jia, Wei Hua

AU - Matsuda, Koichi

AU - Kweon, Sun Seog

AU - Matsuo, Keitaro

AU - Xiang, Yong Bing

AU - Shin, Aesun

AU - Jee, Sun Ha

AU - Kim, Dong Hyun

AU - Cai, Qiuyin

AU - Long, Jirong

AU - Shi, Jiajun

AU - Wen, Wanqing

AU - Yang, Gong

AU - Zhang, Yanfeng

AU - Li, Chun

AU - Li, Bingshan

AU - Guo, Yan

AU - Ren, Zefang

AU - Ji, Bu Tian

AU - Pan, Zhi Zhong

AU - Takahashi, Atsushi

AU - Shin, Min Ho

AU - Matsuda, Fumihiko

AU - Gao, Yu Tang

AU - Oh, Jae Hwan

AU - Kim, Soriul

AU - Ahn, Yoon Ok

AU - Chan, Andrew T.

AU - Chang-Claude, Jenny

AU - Slattery, Martha L.

AU - Gruber, Stephen B.

AU - Schumacher, Fredrick R.

AU - Stenzel, Stephanie L.

AU - Casey, Graham

AU - Kim, Hyeong Rok

AU - Jeong, Jin Young

AU - Park, Ji Won

AU - Li, Hong Lan

AU - Hosono, Satoyo

AU - Cho, Sang Hee

AU - Kubo, Michiaki

AU - Shu, Xiao Ou

AU - Zeng, Yi Xin

AU - Zheng, Wei

PY - 2014/6

Y1 - 2014/6

N2 - 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.

AB - 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.

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