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Probing the diabetes and colorectal cancer relationship using gene - environment interaction analyses
N. Dimou, AE. Kim, O. Flanagan, N. Murphy, V. Diez-Obrero, A. Shcherbina, EK. Aglago, E. Bouras, PT. Campbell, G. Casey, S. Gallinger, SB. Gruber, MA. Jenkins, Y. Lin, V. Moreno, E. Ruiz-Narvaez, MC. Stern, Y. Tian, KK. Tsilidis, V. Arndt, EL....
Jazyk angličtina Země Anglie, Velká Británie
Typ dokumentu časopisecké články, práce podpořená grantem, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.
Grantová podpora
P01 CA196569
NCI NIH HHS - United States
U01 CA137088
NCI NIH HHS - United States
R01 CA059045
NCI NIH HHS - United States
U01 CA164930
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R01 CA206279
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R01 CA201407
NCI NIH HHS - United States
P30 CA015704
NCI NIH HHS - United States
S10 OD028685
NIH HHS - United States
U01 CA086308
NCI NIH HHS - United States
P30 CA006973
NCI NIH HHS - United States
U01 AG018033
NIA NIH HHS - United States
U01 CA167551
NCI NIH HHS - United States
U01 CA122839
NCI NIH HHS - United States
R01 CA143237
NCI NIH HHS - United States
U19 CA148107
NCI NIH HHS - United States
R01 CA081488
NCI NIH HHS - United States
HHSN268201200008I
NHLBI NIH HHS - United States
U01 CA074794
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U24 CA074794
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P30 CA014089
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R01 CA197350
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R01 CA242218
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T32 ES013678
NIEHS NIH HHS - United States
14136
Cancer Research UK - United Kingdom
1000143
Medical Research Council - United Kingdom
P01 CA055075
NCI NIH HHS - United States
UM1 CA167552
NCI NIH HHS - United States
U01 CA167552
NCI NIH HHS - United States
R01 CA137178
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R01 CA151993
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R35 CA197735
NCI NIH HHS - United States
P01 CA087969
NCI NIH HHS - United States
UM1 CA186107
NCI NIH HHS - United States
R01 CA072520
NCI NIH HHS - United States
R01 CA136726
NCI NIH HHS - United States
C588/A19167
Cancer Research UK - United Kingdom
R37 CA054281
NCI NIH HHS - United States
P01 CA033619
NCI NIH HHS - United States
U01 CA063464
NCI NIH HHS - United States
R01 CA066635
NCI NIH HHS - United States
P30 DK034987
NIDDK NIH HHS - United States
U01 CA074783
NCI NIH HHS - United States
U01 HG004446
NHGRI NIH HHS - United States
U01 HG004438
NHGRI NIH HHS - United States
U10 CA037429
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UM1 CA182883
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R01 CA097325
NCI NIH HHS - United States
R03 CA153323
NCI NIH HHS - United States
K05 CA152715
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KL2 TR000421
NCATS NIH HHS - United States
K05 CA154337
NCI NIH HHS - United States
HHSN268201600018C
NHLBI NIH HHS - United States
HHSN268201600001C
NHLBI NIH HHS - United States
HHSN268201600002C
NHLBI NIH HHS - United States
HHSN268201600003C
NHLBI NIH HHS - United States
HHSN268201600004C
NHLBI NIH HHS - United States
R01 CA155101
NCI NIH HHS - United States
C18281/A29019
Cancer Research UK - United Kingdom
P01 CA196569
NCI NIH HHS - United States
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- MeSH
- celogenomová asociační studie metody MeSH
- diabetes mellitus * genetika MeSH
- genetická predispozice k nemoci MeSH
- interakce genů a prostředí MeSH
- jednonukleotidový polymorfismus MeSH
- kolorektální nádory * genetika MeSH
- lidé MeSH
- mikrofilamentové proteiny genetika MeSH
- rizikové faktory MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, U.S. Gov't, P.H.S. MeSH
BACKGROUND: Diabetes is an established risk factor for colorectal cancer. However, the mechanisms underlying this relationship still require investigation and it is not known if the association is modified by genetic variants. To address these questions, we undertook a genome-wide gene-environment interaction analysis. METHODS: We used data from 3 genetic consortia (CCFR, CORECT, GECCO; 31,318 colorectal cancer cases/41,499 controls) and undertook genome-wide gene-environment interaction analyses with colorectal cancer risk, including interaction tests of genetics(G)xdiabetes (1-degree of freedom; d.f.) and joint testing of Gxdiabetes, G-colorectal cancer association (2-d.f. joint test) and G-diabetes correlation (3-d.f. joint test). RESULTS: Based on the joint tests, we found that the association of diabetes with colorectal cancer risk is modified by loci on chromosomes 8q24.11 (rs3802177, SLC30A8 - ORAA: 1.62, 95% CI: 1.34-1.96; ORAG: 1.41, 95% CI: 1.30-1.54; ORGG: 1.22, 95% CI: 1.13-1.31; p-value3-d.f.: 5.46 × 10-11) and 13q14.13 (rs9526201, LRCH1 - ORGG: 2.11, 95% CI: 1.56-2.83; ORGA: 1.52, 95% CI: 1.38-1.68; ORAA: 1.13, 95% CI: 1.06-1.21; p-value2-d.f.: 7.84 × 10-09). DISCUSSION: These results suggest that variation in genes related to insulin signaling (SLC30A8) and immune function (LRCH1) may modify the association of diabetes with colorectal cancer risk and provide novel insights into the biology underlying the diabetes and colorectal cancer relationship.
Bioinformatics and Data Science Research Center Bina Nusantara University Jakarta Indonesia
Biostatistics Division Kaiser Permanente Washington Health Research Institute Seattle WA USA
Broad Institute of Harvard and MIT Cambridge MA USA
Cancer Epidemiology Division Cancer Council Victoria Melbourne VIC Australia
Center for Cancer Research Medical University of Vienna Vienna Austria
Center for Gastrointestinal Biology and Disease University of North Carolina Chapel Hill NC USA
CIBER Epidemiología y Salud Pública Madrid Spain
Clalit National Cancer Control Center Haifa Israel
Computer Science Department School of Computer Science Bina Nusantara University Jakarta Indonesia
Consortium for Biomedical Research in Epidemiology and Public Health Barcelona 08908 Spain
Department of Biostatistics University of Washington Seattle WA USA
Department of Clinical Sciences Faculty of Medicine University of Barcelona Barcelona 08908 Spain
Department of Community Medicine and Epidemiology Lady Davis Carmel Medical Center Haifa Israel
Department of Computer Science Stanford University Stanford CA USA
Department of Epidemiology and Population Health Albert Einstein College of Medicine Bronx NY USA
Department of Epidemiology Geisel School of Medicine at Dartmouth Hanover NH USA
Department of Epidemiology Harvard T H Chan School of Public Health Harvard University Boston MA USA
Department of Epidemiology Johns Hopkins Bloomberg School of Public Health Baltimore MD USA
Department of Epidemiology School of Public Health University of Washington Seattle WA USA
Department of Family Medicine University of Virginia Charlottesville VA USA
Department of General Surgery University of Virginia School of Medicine Charlottesville VA USA
Department of Genetics and Genome Sciences Case Western Reserve University Cleveland OH USA
Department of Genetics Stanford University Stanford CA USA
Department of Hygiene and Epidemiology University of Ioannina School of Medicine Ioannina Greece
Department of Laboratory Medicine and Pathology Mayo Clinic Arizona Scottsdale AZ USA
Department of Medicine and Epidemiology University of Pittsburgh Medical Center Pittsburgh PA USA
Department of Nutritional Sciences University of Michigan School of Public Health Ann Arbor MI USA
Department of Population Health Sciences University of Utah Salt Lake City UH USA
Department of Population Science American Cancer Society Atlanta GA USA
Department of Public Health and Primary Care University of Cambridge Cambridge UK
Department of Public Health Sciences Center for Public Health Genomics Charlottesville VA USA
Division of Cancer Epidemiology German Cancer Research Center Heidelberg Germany
Division of Gastroenterology Massachusetts General Hospital and Harvard Medical School Boston MA USA
Division of Human Nutrition and Health Wageningen University and Research Wageningen The Netherlands
Division of Preventive Oncology German Cancer Research Center Heidelberg Germany
Faculty of Medicine and Biomedical Center in Pilsen Charles University Pilsen Czech Republic
German Cancer Consortium Heidelberg Germany
Huntsman Cancer Institute University of Utah Salt Lake City UT USA
Institute of Environmental Medicine Karolinska Institutet Stockholm Sweden
Leeds Institute of Cancer and Pathology University of Leeds Leeds UK
Lunenfeld Tanenbaum Research Institute Mount Sinai Hospital University of Toronto Toronto ON Canada
Medical Faculty Heidelberg Heidelberg University Heidelberg Germany
Memorial University of Newfoundland Discipline of Genetics St John's NL Canada
Nantes Université CHU Nantes Service de Génétique médicale F 44000 Nantes France
Nutrition and Metabolism Branch International Agency for Research on Cancer Lyon France
ONCOBEL Program Bellvitge Biomedical Research Institute L'Hospitalet de Llobregat Barcelona Spain
Public Health Sciences Division Fred Hutchinson Cancer Center Seattle WA USA
Research Centre for Hauora and Health Massey University Wellington New Zealand
Ruth and Bruce Rappaport Faculty of Medicine Technion Israel Institute of Technology Haifa Israel
School of Public Health Capital Medical University Beijing China
School of Public Health Imperial College London London United Kingdom
School of Public Health University of Washington Seattle WA USA
Slone Epidemiology Center at Boston University Boston MA USA
SWOG Statistical Center Fred Hutchinson Cancer Center Seattle WA USA
University Medical Centre Hamburg Eppendorf University Cancer Centre Hamburg Hamburg Germany
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- $a Dimou, Niki $u Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France. DimouN@iarc.who.int $1 https://orcid.org/0000000316789328
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