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

被引：201

作者：

Zhang, Ben ^{[1
]}

Jia, Wei-Hua ^{[2
]}

Matsuda, Koichi ^{[3
]}

Kweon, Sun-Seog ^{[4
,5
]}

Matsuo, Keitaro ^{[6
]}

Xiang, Yong-Bing ^{[7
]}

Shin, Aesun ^{[8
,9
]}

Jee, Sun Ha ^{[10
]}

Kim, Dong-Hyun ^{[11
]}

Cai, Qiuyin ^{[1
]}

Long, Jirong ^{[1
]}

Shi, Jiajun ^{[1
]}

Wen, Wanqing ^{[1
]}

Yang, Gong ^{[1
]}

Zhang, Yanfeng ^{[1
]}

Li, Chun ^{[12
]}

Li, Bingshan ^{[13
]}

Guo, Yan ^{[14
]}

Ren, Zefang ^{[15
]}

Ji, Bu-Tian ^{[16
]}

Pan, Zhi-Zhong ^{[2
]}

Takahashi, Atsushi ^{[17
]}

Shin, Min-Ho ^{[4
]}

Matsuda, Fumihiko ^{[18
]}

Gao, Yu-Tang ^{[7
]}

Oh, Jae Hwan ^{[19
]}

Kim, Soriul ^{[10
]}

Ahn, Yoon-Ok ^{[9
]}

Chan, Andrew T. ^{[20
,21
,22
]}

Chang-Claude, Jenny ^{[23
]}

Slattery, Martha L. ^{[24
]}

Gruber, Stephen B. ^{[25
]}

Schumacher, Fredrick R. ^{[25
]}

Stenzel, Stephanie L. ^{[25
]}

Casey, Graham ^{[25
]}

Kim, Hyeong-Rok ^{[26
]}

Jeong, Jin-Young ^{[11
]}

Park, Ji Won ^{[19
,27
]}

Li, Hong-Lan ^{[7
]}

Hosono, Satoyo ^{[6
]}

Cho, Sang-Hee ^{[28
]}

Kubo, Michiaki ^{[17
]}

Shu, Xiao-Ou ^{[1
]}

Zeng, Yi-Xin ^{[2
]}

Zheng, Wei ^{[1
]}

机构：

[1] Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, Vanderbilt Ingram Canc Ctr,Dept Med,Div Epidemiol, Nashville, TN 37212 USA

[2] Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol South China, Guangzhou 510275, Guangdong, Peoples R China

[3] Univ Tokyo, Inst Med Sci, Ctr Human Genome, Mol Med Lab, Tokyo, Japan

[4] Chonnam Natl Univ, Sch Med, Dept Prevent Med, Kwangju, South Korea

[5] Chonnam Natl Univ, Hwasun Hosp, Jeonnam Reg Canc Ctr, Hwasun, South Korea

[6] Kyushu Univ, Fac Med Sci, Dept Prevent Med, Fukuoka 812, Japan

[7] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China

[8] Natl Canc Ctr, Mol Epidemiol Branch, Goyang Si, South Korea

[9] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea

[10] Yonsei Univ, Grad Sch Publ Hlth, Inst Hlth Promot, Dept Epidemiol & Hlth Promot, Seoul 120749, South Korea

[11] Hallym Univ, Coll Med, Dept Social & Prevent Med, Okcheon Dong, South Korea

[12] Vanderbilt Univ, Sch Med, Dept Biostat, Nashville, TN 37212 USA

[13] Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37212 USA

[14] Vanderbilt Univ, Sch Med, Dept Canc Biol, Nashville, TN 37212 USA

[15] Sun Yat Sen Univ, Sch Publ Hlth, Guangzhou 510275, Guangdong, Peoples R China

[16] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA

[17] RIKEN, Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan

[18] Kyoto Univ, Grad Sch Med, Ctr Genom Med, Kyoto, Japan

[19] Natl Canc Ctr, Ctr Colorectal Canc, Goyang Si, South Korea

[20] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA

[21] Harvard Univ, Sch Med, Boston, MA USA

[22] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA

[23] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany

[24] Univ Utah, Hlth Sci Ctr, Dept Internal Med, Salt Lake City, UT USA

[25] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA

[26] Chonnam Natl Univ, Sch Med, Dept Surg, Kwangju, South Korea

[27] Seoul Natl Univ Hosp, Dept Surg, Seoul 110744, South Korea

[28] Chonnam Natl Univ, Sch Med, Dept Hematooncol, Kwangju, South Korea

来源：

NATURE GENETICS | 2014年 / 46卷 / 06期

基金：

新加坡国家研究基金会; 美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; LYMPHOTOXIN-BETA-RECEPTOR; SUSCEPTIBILITY LOCI; CELL-GROWTH; EXPRESSION; VARIANTS; MUTATIONS; METAANALYSIS; PROLIFERATION; NUCLEOREDOXIN;

D O I：

10.1038/ng.2985

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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 x 10(-8) to 9.22 x 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.

引用

页码：533 / 542

页数：10

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