Large-scale genetic study in East Asians identifies six new loci associated with colorectal cancer risk.
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.
Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Ben
B
Zhang
State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China.
Wei-Hua
WH
Jia
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Koichi
0000000172922686
K
Matsuda
1] Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, South Korea. [2] Jeonnam Regional Cancer Center, Chonnam National University Hwasun Hospital, Hwasun, South Korea.
Sun-Seog
SS
Kweon
Department of Preventive Medicine, Kyushu University Faculty of Medical Sciences, Fukuoka, Japan.
Keitaro
K
Matsuo
Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China.
Yong-Bing
YB
Xiang
1] Molecular Epidemiology Branch, National Cancer Center, Goyang-si, South Korea. [2] Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, South Korea.
Aesun
A
Shin
Department of Epidemiology and Health Promotion, Institute for Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, South Korea.
Sun Ha
SH
Jee
Department of Social and Preventive Medicine, Hallym University College of Medicine, Okcheon-dong, South Korea.
Dong-Hyun
DH
Kim
Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Qiuyin
Q
Cai
Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Jirong
J
Long
Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Jiajun
0000000151940009
J
Shi
Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Wanqing
W
Wen
Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Gong
G
Yang
Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Yanfeng
Y
Zhang
Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Chun
C
Li
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Bingshan
B
Li
Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Yan
Y
Guo
School of Public Health, Sun Yat-sen University, Guangzhou, China.
Zefang
Z
Ren
Division of Cancer Epidemiology & Genetics, National Cancer Institute, Bethesda, Maryland, USA.
Bu-Tian
BT
Ji
State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China.
Zhi-Zhong
ZZ
Pan
Center for Integrative Medical Sciences, RIKEN, Kanagawa, Japan.
Atsushi
A
Takahashi
Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, South Korea.
Min-Ho
MH
Shin
Center for Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Fumihiko
F
Matsuda
Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China.
Yu-Tang
YT
Gao
Center for Colorectal Cancer, National Cancer Center, Goyang-si, South Korea.
Jae Hwan
JH
Oh
Department of Epidemiology and Health Promotion, Institute for Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, South Korea.
Soriul
S
Kim
Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, South Korea.
Yoon-Ok
YO
Ahn
1] Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. [2] Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Andrew T
AT
Chan
Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.
Jenny
J
Chang-Claude
Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, Utah, USA.
Martha L
ML
Slattery
University of Southern California Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California, USA.
Stephen B
SB
Gruber
University of Southern California Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California, USA.
Fredrick R
FR
Schumacher
University of Southern California Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California, USA.
Stephanie L
SL
Stenzel
University of Southern California Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California, USA.
Graham
G
Casey
Department of Surgery, Chonnam National University Medical School, Gwangju, South Korea.
Hyeong-Rok
HR
Kim
Department of Social and Preventive Medicine, Hallym University College of Medicine, Okcheon-dong, South Korea.
Jin-Young
JY
Jeong
1] Center for Colorectal Cancer, National Cancer Center, Goyang-si, South Korea. [2] Department of Surgery, Seoul National University Hospital, Seoul, South Korea.
Ji Won
JW
Park
Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China.
Hong-Lan
HL
Li
Department of Preventive Medicine, Kyushu University Faculty of Medical Sciences, Fukuoka, Japan.
Satoyo
S
Hosono
Department of Hemato-oncology, Chonnam National University Medical School, Gwangju, South Korea.
Sang-Hee
SH
Cho
Center for Integrative Medical Sciences, RIKEN, Kanagawa, Japan.
Michiaki
M
Kubo
Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Xiao-Ou
XO
Shu
State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China.
Yi-Xin
YX
Zeng
Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Wei
W
Zheng
D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002681:China; D002874:Chromosome Mapping; D015179:Colorectal Neoplasms / Q000208:ethnology* / Q000235:genetics*; D019295:Computational Biology; D000090943:Delta-5 Fatty Acid Desaturase; D005260:Female; D020869:Gene Expression Profiling; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D009362:Neoplasm Metastasis; D020641:Polymorphism, Single Nucleotide; D056910:Republic of Korea; D012306:Risk