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Identification of Novel Loci and New Risk Variant in Known Loci for Colorectal Cancer Risk in East Asians
Y. Lu, SS. Kweon, Q. Cai, C. Tanikawa, XO. Shu, WH. Jia, YB. Xiang, JR. Huyghe, TA. Harrison, J. Kim, A. Shin, DH. Kim, K. Matsuo, SH. Jee, X. Guo, W. Wen, J. Shi, B. Li, N. Wang, MH. Shin, HL. Li, Z. Ren, JH. Oh, I. Oze, YO. Ahn, KJ. Jung, J....
Language English Country United States
Document type Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.
Grant support
R01 CA067941
NCI NIH HHS - United States
U01 HG004438
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U01 HG004446
NHGRI NIH HHS - United States
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HHSN268201100001I
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R01 CA076366
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R01 CA188214
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R35 CA197735
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C570/A16491
Cancer Research UK - United Kingdom
U10 CA037429
NCI NIH HHS - United States
R01 CA114347
NCI NIH HHS - United States
R01 CA072520
NCI NIH HHS - United States
R01 CA082729
NCI NIH HHS - United States
P01 CA087969
NCI NIH HHS - United States
14136
Cancer Research UK - United Kingdom
MR/N003284/1
Medical Research Council - United Kingdom
P30 CA015704
NCI NIH HHS - United States
HHSN268201100004I
NHLBI NIH HHS - United States
P30 CA006973
NCI NIH HHS - United States
K05 CA154337
NCI NIH HHS - United States
C8221/A19170
Cancer Research UK - United Kingdom
P01 CA055075
NCI NIH HHS - United States
R37 CA070867
NCI NIH HHS - United States
R01 CA151993
NCI NIH HHS - United States
HHSN268201100046C
NHLBI NIH HHS - United States
P30 DK034987
NIDDK NIH HHS - United States
R01 CA048998
NCI NIH HHS - United States
U01 CA137088
NCI NIH HHS - United States
R01 CA189184
NCI NIH HHS - United States
U01 CA167552
NCI NIH HHS - United States
HHSN268201100003C
WHI NIH HHS - United States
G1000143
Medical Research Council - United Kingdom
Z01 CP010200
Intramural NIH HHS - United States
UM1 CA173640
NCI NIH HHS - United States
U01 CA164930
NCI NIH HHS - United States
R01 CA092585
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R01 CA066635
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NCI NIH HHS - United States
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NHLBI NIH HHS - United States
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NCI NIH HHS - United States
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NCI NIH HHS - United States
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NCI NIH HHS - United States
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Cancer Research UK - United Kingdom
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NCI NIH HHS - United States
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NCI NIH HHS - United States
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NCATS NIH HHS - United States
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NCI NIH HHS - United States
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- MeSH
- Asian People genetics MeSH
- Genome-Wide Association Study MeSH
- Adult MeSH
- Genetic Predisposition to Disease * MeSH
- Genetic Loci * MeSH
- Polymorphism, Single Nucleotide MeSH
- Colorectal Neoplasms epidemiology genetics MeSH
- Middle Aged MeSH
- Humans MeSH
- Chromosomes, Human, Pair 1 genetics MeSH
- INDEL Mutation MeSH
- Risk Factors MeSH
- Aged MeSH
- Case-Control Studies MeSH
- Linkage Disequilibrium MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, N.I.H., Intramural MeSH
- Research Support, U.S. Gov't, P.H.S. MeSH
- Geographicals
- China MeSH
- Japan MeSH
- Republic of Korea MeSH
BACKGROUND: Risk variants identified so far for colorectal cancer explain only a small proportion of familial risk of this cancer, particularly in Asians. METHODS: We performed a genome-wide association study (GWAS) of colorectal cancer in East Asians, including 23,572 colorectal cancer cases and 48,700 controls. To identify novel risk loci, we selected 60 promising risk variants for replication using data from 58,131 colorectal cancer cases and 67,347 controls of European descent. To identify additional risk variants in known colorectal cancer loci, we performed conditional analyses in East Asians. RESULTS: An indel variant, rs67052019 at 1p13.3, was found to be associated with colorectal cancer risk at P = 3.9 × 10-8 in Asians (OR per allele deletion = 1.13, 95% confidence interval = 1.08-1.18). This association was replicated in European descendants using a variant (rs2938616) in complete linkage disequilibrium with rs67052019 (P = 7.7 × 10-3). Of the remaining 59 variants, 12 showed an association at P < 0.05 in the European-ancestry study, including rs11108175 and rs9634162 at P < 5 × 10-8 and two variants with an association near the genome-wide significance level (rs60911071, P = 5.8 × 10-8; rs62558833, P = 7.5 × 10-8) in the combined analyses of Asian- and European-ancestry data. In addition, using data from East Asians, we identified 13 new risk variants at 11 loci reported from previous GWAS. CONCLUSIONS: In this large GWAS, we identified three novel risk loci and two highly suggestive loci for colorectal cancer risk and provided evidence for potential roles of multiple genes and pathways in the etiology of colorectal cancer. In addition, we showed that additional risk variants exist in many colorectal cancer risk loci identified previously. IMPACT: Our study provides novel data to improve the understanding of the genetic basis for colorectal cancer risk.
Broad Institute of Harvard and MIT Cambridge Massachusetts
Case Comprehensive Cancer Center Case Western Reserve University Cleveland Ohio
CIBER Epidemiología y Salud Pública Madrid Spain
Department of Biostatistics University of Washington Seattle Washington
Department of Clinical Genetics Karolinska University Hospital Stockholm Sweden
Department of Clinical Sciences Faculty of Medicine University of Barcelona Barcelona Spain
Department of Epidemiology Nagoya University Graduate School of Medicine Nagoya Japan
Department of Epidemiology University of Washington Seattle Washington
Department of Medicine 1 University Hospital Dresden Technische Universität Dresden Dresden Germany
Department of Medicine Weill Cornell Medical College New York New York
Department of Molecular Medicine and Surgery Karolinska Institutet Stockholm Sweden
Department of Preventive Medicine Chonnam National University Medical School Gwangju South Korea
Department of Preventive Medicine Seoul National University College of Medicine Seoul South Korea
Department of Public Health and Primary Care University of Cambridge Cambridge United Kingdom
Department of Radiation Sciences Oncology Unit Umeå University Umeå Sweden
Division of Cancer Epidemiology and Genetics National Cancer Institute NIH Bethesda Maryland
Division of Human Nutrition Wageningen University and Research Wageningen the Netherlands
Division of Molecular and Clinical Epidemiology Aichi Cancer Center Research Institute Nagoya Japan
Faculty of Medicine and Biomedical Center in Pilsen Charles University Pilsen Czech Republic
General Surgery Department Tangdu Hospital 4th Military Medical University Xi'an Shaanxi China
Institute for Health Promotion Graduate School of Public Health Yonsei University Seoul Korea
Institute of Cancer Research Department of Medicine 1 Medical University Vienna Vienna Austria
Institute of Environmental Medicine Karolinska Institutet Stockholm Sweden
Jeonnam Regional Cancer Center Chonnam National University Hwasun Hospital Hwasun South Korea
Laboratory for Statistical Analysis RIKEN Center for Integrative Medical Sciences Kanagawa Japan
Public Health Sciences Division Fred Hutchinson Cancer Research Center Seattle Washington
School of Public Health Sun Yat sen University Guangzhou China
School of Public Health University of Washington Seattle Washington
State Key Laboratory of Oncology in South China Cancer Center Sun Yat sen University Guangzhou China
University of Hawaii Cancer Center Honolulu Hawaii
University of Southern California Preventative Medicine Los Angeles California
References provided by Crossref.org
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