Genetic architectures of proximal and distal colorectal cancer are partly distinct
Jazyk angličtina Země Anglie, Velká Británie Médium print-electronic
Typ dokumentu časopisecké články, metaanalýza, Research Support, N.I.H., Extramural, práce podpořená grantem
Grantová podpora
P01 CA087969
NCI NIH HHS - United States
P30 CA015704
NCI NIH HHS - United States
U01 CA137088
NCI NIH HHS - United States
U01 CA164930
NCI NIH HHS - United States
HHSN268201200008C
NHLBI NIH HHS - United States
UM1 CA186107
NCI NIH HHS - United States
25004
Cancer Research UK - United Kingdom
001
World Health Organization - International
R01 CA059045
NCI NIH HHS - United States
R35 CA197735
NCI NIH HHS - United States
U10 CA037429
NCI NIH HHS - United States
U01 CA182883
NCI NIH HHS - United States
19167
Cancer Research UK - United Kingdom
R00 CA158141
NCI NIH HHS - United States
UG1 CA189974
NCI NIH HHS - United States
R01 CA151993
NCI NIH HHS - United States
R21 CA191312
NCI NIH HHS - United States
U01 CA206110
NCI NIH HHS - United States
P30 CA008748
NCI NIH HHS - United States
U01 CA167551
NCI NIH HHS - United States
R01 CA143237
NCI NIH HHS - United States
R01 CA201407
NCI NIH HHS - United States
R01 CA207371
NCI NIH HHS - United States
16561
Cancer Research UK - United Kingdom
R01 CA042182
NCI NIH HHS - United States
K99 CA158141
NCI NIH HHS - United States
UM1 CA182883
NCI NIH HHS - United States
K07 CA190673
NCI NIH HHS - United States
HHSN268201200008I
NHLBI NIH HHS - United States
P30 CA071789
NCI NIH HHS - United States
PubMed
33632709
PubMed Central
PMC8223655
DOI
10.1136/gutjnl-2020-321534
PII: gutjnl-2020-321534
Knihovny.cz E-zdroje
- Klíčová slova
- cancer genetics, cancer susceptibility, colon carcinogenesis, colorectal cancer, genetic polymorphisms,
- MeSH
- alely MeSH
- běloši genetika MeSH
- cékum MeSH
- celogenomová asociační studie MeSH
- colon ascendens MeSH
- colon descendens MeSH
- colon sigmoideum MeSH
- colon transversum MeSH
- dospělí MeSH
- genetická heterogenita * MeSH
- genotyp MeSH
- jednonukleotidový polymorfismus MeSH
- kolon * MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- nádory rekta diagnóza genetika MeSH
- nádory tračníku diagnóza genetika MeSH
- rizikové faktory MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- věk při počátku nemoci MeSH
- věkové rozložení MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
OBJECTIVE: An understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk factors among tumors arising in different locations of the colorectum suggest partly distinct mechanisms of carcinogenesis. The extent to which the contribution of inherited genetic risk factors for CRC differs by anatomical subsite of the primary tumor has not been examined. DESIGN: To identify new anatomical subsite-specific risk loci, we performed genome-wide association study (GWAS) meta-analyses including data of 48 214 CRC cases and 64 159 controls of European ancestry. We characterised effect heterogeneity at CRC risk loci using multinomial modelling. RESULTS: We identified 13 loci that reached genome-wide significance (p<5×10-8) and that were not reported by previous GWASs for overall CRC risk. Multiple lines of evidence support candidate genes at several of these loci. We detected substantial heterogeneity between anatomical subsites. Just over half (61) of 109 known and new risk variants showed no evidence for heterogeneity. In contrast, 22 variants showed association with distal CRC (including rectal cancer), but no evidence for association or an attenuated association with proximal CRC. For two loci, there was strong evidence for effects confined to proximal colon cancer. CONCLUSION: Genetic architectures of proximal and distal CRC are partly distinct. Studies of risk factors and mechanisms of carcinogenesis, and precision prevention strategies should take into consideration the anatomical subsite of the tumour.
Behavioral and Epidemiology Research Group American Cancer Society Atlanta Georgia USA
Broad Institute of Harvard and MIT Cambridge Massachusetts USA
Cancer Epidemiology Division Cancer Council Victoria Melbourne Victoria Australia
Cancer Epidemiology Unit Nuffield Department of Population Health University of Oxford Oxford UK
Center for Public Health Genomics University of Virginia Charlottesville Virginia USA
CIBER Epidemiología y Salud Pública Madrid Spain
City of Hope National Medical Center Duarte California USA
Clalit National Cancer Control Center Haifa Israel
Clinical Research Division Fred Hutchinson Cancer Research Center Seattle Washington USA
Department of Biostatistics University of Washington Seattle Washington USA
Department of Clinical Genetics Karolinska University Hospital Stockholm Sweden
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 USA
Department of Epidemiology and Biostatistics Imperial College London London UK
Department of Epidemiology German Institute of Human Nutrition Potsdam Rehbrücke Germany
Department of Epidemiology University of Washington Seattle Washington USA
Department of Family Medicine University of Virginia Charlottesville Virginia USA
Department of General Surgery University Hospital Rostock Rostock Germany
Department of Genetics Stanford University Stanford California USA
Department of Genome Sciences University of Washington Seattle Washington USA
Department of Health Science Research Mayo Clinic Scottsdale Arizona USA
Department of Internal Medicine University of Utah Health Salt Lake City Utah USA
Department of Medicine 1 University Hospital Dresden Technische Universität Dresden Dresden Germany
Department of Medicine University of Washington School of Medicine Seattle Washington USA
Department of Medicine Weill Cornell Medical College New York New York USA
Department of Molecular Medicine and Surgery Karolinska Institutet Stockholm Sweden
Department of Oncologic Pathology Dana Farber Cancer Institute Boston Massachusetts USA
Department of Pathology School of Medicine Umm Al Qura'a University Mecca Saudi Arabia
Department of Public Health and Primary Care University of Cambridge Cambridge UK
Department of Public Health Solutions National Institute for Health and Welfare Helsinki Finland
Department of Radiation Sciences Oncology Unit Umeå University Umeå Sweden
Dipartimento di Medicina Clinica e Chirurgia University of Naples Federico 2 Naples Italy
Discipline of Genetics Memorial University of Newfoundland St John's Newfoundland Canada
Division of Cancer Control and Population Sciences National Cancer Institute Bethesda Maryland USA
Division of Cancer Epidemiology and Genetics National Cancer Institute Bethesda Maryland USA
Division of Cancer Epidemiology German Cancer Research Centre Heidelberg Germany
Division of Clinical Epidemiology German Cancer Research Centre Heidelberg Germany
Division of Epidemiology and Community Health University of Minnesota Minneapolis Minnesota USA
Division of Human Nutrition and Health Wageningen University and Research Wageningen The Netherlands
Division of Preventive Oncology German Cancer Research Centre Heidelberg Germany
Division of Research Kaiser Permanente Medical Care Program Oakland California USA
Division of Research Kaiser Permanente Northern California Oakland California USA
Faculty of Medicine and Biomedical Center in Pilsen Charles University Pilsen Czech Republic
Genomic Medicine and Family Cancer Clinic Royal Melbourne Hospital Melbourne Victoria Australia
Genomic Medicine Institute Cleveland Clinic Cleveland Ohio USA
German Cancer Consortium Heidelberg Germany
Hellenic Health Foundation Athens Greece
Institut Gustave Roussy Université Paris Saclay Villejuif France
Institute for Health Research Kaiser Permanente Colorado Denver Colorado USA
Institute of Cancer Research Department of Medicine 1 Medical University of Vienna Vienna Austria
Institute of Environmental Medicine Karolinska Institutet Stockholm Sweden
Institute of Epidemiology PopGen Biobank Christian Albrechts University Kiel Kiel Germany
Laboratoire de Mathématiques Appliquées MAP5 Université Paris Descartes Paris France
Leeds Institute of Medical Research at St James's University of Leeds Leeds UK
Medical Faculty University of Heidelberg Heidelberg Germany
Ontario Institute for Cancer Research Toronto Ontario Canada
Public Health Division of Gipuzkoa Health Department of Basque Country San Sebastian Spain
Public Health Sciences Division Fred Hutchinson Cancer Research Center Seattle Washington USA
Ruth and Bruce Rappaport Faculty of Medicine Technion Israel Institute of Technology Haifa Israel
School of Public Health Imperial College London London UK
Service de Génétique Médicale Centre Hospitalier Universitaire de Nantes Nantes France
SWOG Statistical Center Fred Hutchinson Cancer Research Center Seattle Washington USA
The Clalit Health Services Personalized Genomic Service Carmel Medical Center Haifa Israel
Translational Genomics Research Institute An Affiliate of City of Hope Phoenix Arizona USA
University of Hawai'i Cancer Center Honolulu Hawaii USA
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