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Genome-wide Interaction Study with Smoking for Colorectal Cancer Risk Identifies Novel Genetic Loci Related to Tumor Suppression, Inflammation, and Immune Response
R. Carreras-Torres, AE. Kim, Y. Lin, V. Díez-Obrero, SA. Bien, C. Qu, J. Wang, N. Dimou, EK. Aglago, D. Albanes, V. Arndt, JW. Baurley, SI. Berndt, S. Bézieau, DT. Bishop, E. Bouras, H. Brenner, A. Budiarto, PT. Campbell, G. Casey, AT. Chan, J....
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, práce podpořená grantem
Grantová podpora
U01 CA182883
NCI NIH HHS - United States
R01 CA151993
NCI NIH HHS - United States
U01 CA137088
NCI NIH HHS - United States
U01 CA164930
NCI NIH HHS - United States
R21 CA191312
NCI NIH HHS - United States
R01 CA137178
NCI NIH HHS - United States
R01 CA081488
NCI NIH HHS - United States
R01 CA201407
NCI NIH HHS - United States
U01 CA086308
NCI NIH HHS - United States
14136
Cancer Research UK - United Kingdom
R35 CA253185
NCI NIH HHS - United States
U19 CA148107
NCI NIH HHS - United States
R01 CA059045
NCI NIH HHS - United States
R01 CA197350
NCI NIH HHS - United States
R01 CA248857
NCI NIH HHS - United States
P30 CA015704
NCI NIH HHS - United States
P30 CA006973
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
- genetická predispozice k nemoci * MeSH
- genetické lokusy MeSH
- genotyp MeSH
- jednonukleotidový polymorfismus MeSH
- kolorektální nádory * epidemiologie MeSH
- kouření tabáku MeSH
- kouření genetika MeSH
- lidé MeSH
- rizikové faktory MeSH
- studie případů a kontrol MeSH
- zánět MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
BACKGROUND: Tobacco smoking is an established risk factor for colorectal cancer. However, genetically defined population subgroups may have increased susceptibility to smoking-related effects on colorectal cancer. METHODS: A genome-wide interaction scan was performed including 33,756 colorectal cancer cases and 44,346 controls from three genetic consortia. RESULTS: Evidence of an interaction was observed between smoking status (ever vs. never smokers) and a locus on 3p12.1 (rs9880919, P = 4.58 × 10-8), with higher associated risk in subjects carrying the GG genotype [OR, 1.25; 95% confidence interval (CI), 1.20-1.30] compared with the other genotypes (OR <1.17 for GA and AA). Among ever smokers, we observed interactions between smoking intensity (increase in 10 cigarettes smoked per day) and two loci on 6p21.33 (rs4151657, P = 1.72 × 10-8) and 8q24.23 (rs7005722, P = 2.88 × 10-8). Subjects carrying the rs4151657 TT genotype showed higher risk (OR, 1.12; 95% CI, 1.09-1.16) compared with the other genotypes (OR <1.06 for TC and CC). Similarly, higher risk was observed among subjects carrying the rs7005722 AA genotype (OR, 1.17; 95% CI, 1.07-1.28) compared with the other genotypes (OR <1.13 for AC and CC). Functional annotation revealed that SNPs in 3p12.1 and 6p21.33 loci were located in regulatory regions, and were associated with expression levels of nearby genes. Genetic models predicting gene expression revealed that smoking parameters were associated with lower colorectal cancer risk with higher expression levels of CADM2 (3p12.1) and ATF6B (6p21.33). CONCLUSIONS: Our study identified novel genetic loci that may modulate the risk for colorectal cancer of smoking status and intensity, linked to tumor suppression and immune response. IMPACT: These findings can guide potential prevention treatments.
Behavioral and Epidemiology Research Group American Cancer Society Atlanta Georgia
Bioinformatics and Data Science Research Center Bina Nusantara University Jakarta Indonesia
Broad Institute of MIT and Harvard Cambridge Massachusetts
Cancer Epidemiology Division Cancer Council Victoria Melbourne Victoria Australia
Consortium for Biomedical Research in Epidemiology and Public Health Madrid Spain
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 Epidemiology Harvard T H Chan School of Public Health Boston Massachusetts
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 Family Medicine University of Virginia Charlottesville Virginia
Department of General Surgery University of Virginia School of Medicine Charlottesville Virginia
Department of Genetics and Genome Sciences Case Western Reserve University Cleveland Ohio
Department of Genetics Department of Computer Science 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 Oncologic Pathology Dana Farber Cancer Institute Boston Massachusetts
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
Digestive Diseases and Microbiota Group Girona Biomedical Research Institute Salt Girona Spain
Division of Cancer Epidemiology and Genetics NCI NIH Bethesda Maryland
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
Genomic Medicine Institute Cleveland Clinic Cleveland Ohio
German Cancer Consortium Heidelberg Germany
Huntsman Cancer Institute 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
Leeds Institute of Cancer and Pathology University of Leeds Leeds United Kingdom
Memorial University of Newfoundland Discipline of Genetics St John's Canada
Nutrition and Metabolism Branch International Agency for Research on Cancer Lyon France
Population and Cancer Prevention Program Case Comprehensive Cancer Center Cleveland Ohio
Public Health Sciences Division Fred Hutchinson Cancer Research Center Seattle Washington
School of Public Health Capital Medical University Beijing P R China
School of Public Health University of Washington Seattle Washington
Service de Génétique Médicale Centre Hospitalier Universitaire Nantes Nantes France
Slone Epidemiology Center at Boston University Boston Massachusetts
SWOG Statistical Center Fred Hutchinson Cancer Research Center Seattle Washington
University of Hawaii Cancer Center Honolulu Hawaii
Wallenberg Centre for Molecular Medicine Umeå University Umeå Sweden
Citace poskytuje Crossref.org
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