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Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2019 Dec 11. pii: 1055-9965.EPI-19-0755. doi: 10.1158/1055-9965.EPI-19-0755
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Identification of novel loci and new risk variant in known loci for colorectal cancer risk in East Asians.
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Lu Y1, Kweon SS2, Cai Q3, Tanikawa C4, Shu XO5, Jia WH6, Xiang YB7, Huyghe JR8, Harrison TA9, Kim J10, Shin A11, Kim DH12, Matsuo K13, Jee SH14, Guo X15, Wen W16, Shi J17, Li B18, Wang N19, Shin MH20, Li HL21, Ren ZF22, Hwan Oh J23, Oze I24, Ahn YO25, Jung KJ26, Gao J27, Gao YT28, Pan ZZ29, Kamatani Y30, Chan AT31, Gsur A32, Hampe J33, Le Marchand L34, Li L35, Lindblom A36, Moreno V37, Newcomb PA38, Offit K39, Pharoah PDP40, van Duijnhoven FJB41, Van Guelpen B42, Vodicka PE43, Weinstein SJ44, Wolk A45, Wu AH46, Hsu L47, Zeng YX48, Long J49, Peters U50, Matsuda K51, Zheng W52 |
  Author information
1Department of Medicine, Vanderbilt University Medical Center.
2Department of Preventive Medicine, Chonnam National University Medical School.
3Department of Medicine, Vanderbilt University Medical Center.
4Laboratory of Molecular Medicine, Institute of Medical Science, The university of Tokyo.
5Department of Medicine, Vanderbilt University School of Medicine.
6Cancer Center, Sun Yat-sen.
7Department of Epidemiology, Shanghai Cancer Institute.
8Public Health Sciences Division, Fred Hutchinson Cancer Research Center.
9Public Health Sciences, Fred Hutchinson Cancer Research Center.
10Cancer Biomedical Science, National Cancer Center.
11Department of Preventive Medicine, Seoul National University College of Medicine.
12Social and Preventive Medicine, Hallym University College of Medicine.
13Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute.
14Institute for Health Promotion, Graduate School of Public Health, Yonsei University.
15Department of Medicine, Vanderbilt University Medical Center.
16Vanderbilt University Medical Center.
17Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine.
18Vanderbilt University.
19Tangdu Hospital, FMMU.
20Preventive Medicine, Chonnam National University Medical School.
21Department of Epidemiology, Shanghai Cancer Institute.
22School of Public Health, Sun Yat-sen University.
23Seoul National University College of Medicine.
24Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute.
25Department of Preventive Medicine, Seoul National University College of Medicine.
26Institute for Health Promotion, Graduate School of Public Health, Yonsei University.
27Shanghai Cancer Institute.
28Department of Epidemiology, Shanghai Cancer Institute.
29State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University.
30RIKEN.
31Massachusetts General Hospital.
32Department of Medicine I, Institute of Cancer Research, Medical University of Vienna.
33Medical Department 1, University Hospital Dresden.
34Department of Epidemiology, University of Hawaii Cancer Center.
35Department of Family Medicine and Division of Genetic Epidemiology, Case Western Reserve University.
36Department of Molecular Medicine and Surgery, Karolinska Institute.
37Oncology Data Analytics Program, Catalan Institute of Oncology.
38Public Health Sciences Division, Fred Hutchinson Cancer Research Center.
39Medicine, Memorial Sloan Kettering Cancer Center.
40Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge.
41Division of Human Nutrition, Wageningen University & Research.
42Department of Radiation Sciences, Oncology, Umeå University.
43Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences.
44Division of Cancer Epidemiology, National Cancer Institute.
45Institute of Environmental Medicine, Karolinska Institute.
46Department of Preventive Medicine, University of Southern California Keck School of Medicine.
47Public Health Sciences Division, Fred Hutchinson Cancer Research Center.
48Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center.
49Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center.
50Public Health Sciences Division, Fred Hutchinson Cancer Research Center.
51Laboratory of Clinical genome Sequencing, University of Tokyo.
52Department of Medicine, Vanderbilt University Medical Center wei.zheng@vanderbilt.edu.
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Abstract
BACKGROUND: Risk variants identified so far for colorectal cancer (CRC) explain only a small proportion of familial risk of this cancer, particularly in Asians.
METHODS: We performed a genome-wide association study (GWAS) of CRC in East Asians including 23,572 CRC cases and 48,700 controls. To identify novel risk loci, we selected sixty promising risk variants for replication using data from 58,131 CRC cases and 67,347 controls of European descent. To identify additional risk variants in known CRC loci, we performed conditional analyses in East Asians.
RESULTS: An indel variant, rs67052019 at 1p13.3, was found to be associated with CRC risk at P=3.9 x 10-8 in Asians (OR per allele deletion=1.13, 95%CI=1.08-1.18). This association was replicated in European descendants using a variant (rs2938616) in complete linkage disequilibrium with rs67052019 (P=7.7 x 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 CRC risk and provided evidence for potential roles of multiple genes and pathways in the etiology of CRC.
IMPACT: Our study provides novel data to improve the understanding of the genetic basis for CRC risk.
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Copyright ©2019, American Association for Cancer Research.
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Publikations ID: 31826910
Quelle: öffnen
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