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Beyond GWAS of Colorectal Cancer: Evidence of Interaction with Alcohol Consumption and Putative Causal Variant for the 10q24.2 Region
KM. Jordahl, A. Shcherbina, AE. Kim, YR. Su, Y. Lin, J. Wang, C. Qu, D. Albanes, V. Arndt, JW. Baurley, SI. Berndt, SA. Bien, DT. Bishop, E. Bouras, H. Brenner, DD. Buchanan, A. Budiarto, PT. Campbell, R. Carreras-Torres, G. Casey, TW. Cenggoro,...
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, práce podpořená grantem, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.
Grantová podpora
R01 CA059045
NCI NIH HHS - United States
U01 CA182883
NCI NIH HHS - United States
R01 CA206279
NCI NIH HHS - United States
U01 CA137088
NCI NIH HHS - United States
U01 CA164930
NCI NIH HHS - United States
U01 CA206110
NCI NIH HHS - United States
U01 CA167551
NCI NIH HHS - United States
R01 CA201407
NCI NIH HHS - United States
NLK
Free Medical Journals
od 1991 do Před 1 rokem
Freely Accessible Science Journals
od 1991 do Před 12 měsíci
Open Access Digital Library
od 1991-11-01
Open Access Digital Library
od 1991-11-01
- MeSH
- celogenomová asociační studie * MeSH
- jednonukleotidový polymorfismus MeSH
- kolorektální nádory * etiologie genetika MeSH
- lidé MeSH
- pití alkoholu škodlivé účinky epidemiologie genetika MeSH
- respirační komplex IV 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: Currently known associations between common genetic variants and colorectal cancer explain less than half of its heritability of 25%. As alcohol consumption has a J-shape association with colorectal cancer risk, nondrinking and heavy drinking are both risk factors for colorectal cancer. METHODS: Individual-level data was pooled from the Colon Cancer Family Registry, Colorectal Transdisciplinary Study, and Genetics and Epidemiology of Colorectal Cancer Consortium to compare nondrinkers (≤1 g/day) and heavy drinkers (>28 g/day) with light-to-moderate drinkers (1-28 g/day) in GxE analyses. To improve power, we implemented joint 2df and 3df tests and a novel two-step method that modifies the weighted hypothesis testing framework. We prioritized putative causal variants by predicting allelic effects using support vector machine models. RESULTS: For nondrinking as compared with light-to-moderate drinking, the hybrid two-step approach identified 13 significant SNPs with pairwise r2 > 0.9 in the 10q24.2/COX15 region. When stratified by alcohol intake, the A allele of lead SNP rs2300985 has a dose-response increase in risk of colorectal cancer as compared with the G allele in light-to-moderate drinkers [OR for GA genotype = 1.11; 95% confidence interval (CI), 1.06-1.17; OR for AA genotype = 1.22; 95% CI, 1.14-1.31], but not in nondrinkers or heavy drinkers. Among the correlated candidate SNPs in the 10q24.2/COX15 region, rs1318920 was predicted to disrupt an HNF4 transcription factor binding motif. CONCLUSIONS: Our study suggests that the association with colorectal cancer in 10q24.2/COX15 observed in genome-wide association study is strongest in nondrinkers. We also identified rs1318920 as the putative causal regulatory variant for the region. IMPACT: The study identifies multifaceted evidence of a possible functional effect for rs1318920.
Behavioral and Epidemiology Research Group American Cancer Society Atlanta Georgia
Bioinformatics and Data Science Research Center Bina Nusantara University Jakarta Indonesia
BioRealm LLC Walnut California
Broad Institute of Harvard and MIT Cambridge Massachusetts
Broad Institute of MIT and Harvard Cambridge Massachusetts
Cancer Epidemiology Division Cancer Council Victoria Melbourne Victoria Australia
Center for Public Health Genomics University of Virginia Charlottesville Virginia
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 Madrid Spain
Department of Biostatistics University of Washington Seattle Washington
Department of Clinical Sciences Faculty of Medicine University of Barcelona Barcelona Spain
Department of Community Medicine and Epidemiology Lady Davis Carmel Medical Center Haifa Israel
Department of Computer Science Stanford University Stanford California
Department of Epidemiology Johns Hopkins Bloomberg School of Public Health Baltimore Maryland
Department of Epidemiology Richard M Fairbanks School of Public Health Indianapolis Indiana
Department of Epidemiology School of Public Health University of Washington Seattle Washington
Department of Family Medicine University of Virginia Charlottesville Virginia
Department of Genetics and Genome Sciences Case Western Reserve University Cleveland Ohio
Department of Genetics Stanford University Stanford California
Department of Hygiene and Epidemiology University of Ioannina School of Medicine Ioannina Greece
Department of Internal Medicine University of Utah Salt Lake City Utah
Department of Laboratory Medicine and Pathology Mayo Clinic Arizona Scottsdale Arizona
Department of Nutritional Sciences University of Michigan School of Public Health Ann Arbor Michigan
Department of Pathology School of Medicine Umm Al Qura'a University Saudi Arabia
Department of Population Health Sciences University of Utah Salt Lake City Utah
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 German Cancer Research Center Heidelberg Germany
Division of Human Nutrition and Health Wageningen University and Research Wageningen the Netherlands
Division of Preventive Oncology German Cancer Research Center Heidelberg Germany
Division of Research Kaiser Permanente Northern California Oakland California
Faculty of Medicine and Biomedical Center in Pilsen Charles University Pilsen Czech Republic
Genetic Medicine and Family Cancer Clinic The Royal Melbourne Hospital Parkville Victoria Australia
Genomic Medicine Institute Cleveland Clinic Cleveland Ohio
German Cancer Consortium Heidelberg Germany
Harvard Medical School Boston Massachusetts
Huntsman Cancer Institute Salt Lake City Utah
Huntsman Cancer Institute University of Utah Salt Lake City Utah
Institute of Cancer Research Department of Medicine 1 Medical University Vienna Vienna Austria
Institute of Environmental Medicine Karolinska Institutet Stockholm Sweden
IU Melvin and Bren Simon Cancer Center Indiana University Indianapolis Indiana
Leeds Institute of Cancer and Pathology University of Leeds Leeds United Kingdom
Memorial University of Newfoundland Discipline of Genetics St John's Canada
ONCOBEL Program Bellvitge Biomedical Research Institute L'Hospitalet de Llobregat Barcelona Spain
Population and Cancer Prevention Program Case Comprehensive Cancer Center Cleveland Ohio
Public Health Sciences Division Fred Hutchinson Cancer Research Center Seattle Washington
Ruth and Bruce Rappaport Faculty of Medicine Technion Israel Institute of Technology Haifa Israel
School of Public Health Capital Medical University Beijing China
Section of Nutrition and Metabolism International Agency for Research on Cancer Lyon France
Slone Epidemiology Center at Boston University Boston Massachusetts
SWOG Statistical Center Fred Hutchinson Cancer Research Center Seattle Washington
University Medical Centre Hamburg Eppendorf University Cancer Centre Hamburg Hamburg Germany
University of Hawaii Cancer Center Honolulu Hawaii
Wallenberg Centre for Molecular Medicine Umeå University Umeå Sweden
Citace poskytuje Crossref.org
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