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Hepcidin-regulating iron metabolism genes and pancreatic ductal adenocarcinoma: a pathway analysis of genome-wide association studies
S. Julián-Serrano, F. Yuan, W. Wheeler, B. Benyamin, MJ. Machiela, AA. Arslan, LE. Beane-Freeman, PM. Bracci, EJ. Duell, M. Du, S. Gallinger, GG. Giles, PJ. Goodman, C. Kooperberg, LL. Marchand, RE. Neale, XO. Shu, SK. Van Den Eeden, K....
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, práce podpořená grantem, Research Support, U.S. Gov't, Non-P.H.S.
Grantová podpora
R01 HL034595
NHLBI NIH HHS - United States
CA098380
Pancreatic Cancer Cohort II
P30 CA008748
NCI NIH HHS - United States
RO1CA102765
MSKCC
HHSN268201600004C
NHLBI NIH HHS - United States
P30CA008748
Memorial Sloan Kettering Cancer Center
HHSN268201600018C
NHLBI NIH HHS - United States
U01CA164973
NCI NIH HHS - United States
R01 CA049449
NCI NIH HHS - United States
U01CA21017
Hale Center for Pancreatic Cancer Research
R01 CA098380
NCI NIH HHS - United States
UM1 CA182883
NCI NIH HHS - United States
U01 CA247283
NCI NIH HHS - United States
HHSN268201600001C
NHLBI NIH HHS - United States
RO1CA154823
NIH HHS - United States
HHSN268201600003C
NHLBI NIH HHS - United States
R01 CA102765
NCI NIH HHS - United States
HHSN268201600002C
NHLBI NIH HHS - United States
P50 CA102701
NCI NIH HHS - United States
R03 CA123546
NCI NIH HHS - United States
HSN261201000140C
California Department of Public Health
NLK
Free Medical Journals
od 1999 do Před 1 rokem
Freely Accessible Science Journals
od 1999 do Před 1 rokem
Open Access Digital Library
od 1999-01-01
PubMed
34258619
DOI
10.1093/ajcn/nqab217
Knihovny.cz E-zdroje
- MeSH
- adenokarcinom metabolismus MeSH
- genotyp MeSH
- hepcidiny genetika metabolismus MeSH
- jednonukleotidový polymorfismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory slinivky břišní metabolismus MeSH
- regulace genové exprese u nádorů fyziologie MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- vazebná nerovnováha MeSH
- železo metabolismus MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, N.I.H., Intramural MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
BACKGROUND: Epidemiological studies have suggested positive associations for iron and red meat intake with risk of pancreatic ductal adenocarcinoma (PDAC). Inherited pathogenic variants in genes involved in the hepcidin-regulating iron metabolism pathway are known to cause iron overload and hemochromatosis. OBJECTIVES: The objective of this study was to determine whether common genetic variation in the hepcidin-regulating iron metabolism pathway is associated with PDAC. METHODS: We conducted a pathway analysis of the hepcidin-regulating genes using single nucleotide polymorphism (SNP) summary statistics generated from 4 genome-wide association studies in 2 large consortium studies using the summary data-based adaptive rank truncated product method. Our population consisted of 9253 PDAC cases and 12,525 controls of European descent. Our analysis included 11 hepcidin-regulating genes [bone morphogenetic protein 2 (BMP2), bone morphogenetic protein 6 (BMP6), ferritin heavy chain 1 (FTH1), ferritin light chain (FTL), hepcidin (HAMP), homeostatic iron regulator (HFE), hemojuvelin (HJV), nuclear factor erythroid 2-related factor 2 (NRF2), ferroportin 1 (SLC40A1), transferrin receptor 1 (TFR1), and transferrin receptor 2 (TFR2)] and their surrounding genomic regions (±20 kb) for a total of 412 SNPs. RESULTS: The hepcidin-regulating gene pathway was significantly associated with PDAC (P = 0.002), with the HJV, TFR2, TFR1, BMP6, and HAMP genes contributing the most to the association. CONCLUSIONS: Our results support that genetic susceptibility related to the hepcidin-regulating gene pathway is associated with PDAC risk and suggest a potential role of iron metabolism in pancreatic carcinogenesis. Further studies are needed to evaluate effect modification by intake of iron-rich foods on this association.
Cancer Epidemiology Division Cancer Council Victoria Melbourne Australia
CHRISTUS Santa Rosa Hospital Medical Center San Antonio TX USA
CIBER Epidemiología y Salud Pública Barcelona Spain
Consortium for Biomedical Research in Epidemiology and Public Health Madrid Spain
Department of Biology University of Pisa Italy
Department of Biostatistics Harvard T H Chan School of Public Health Boston MA USA
Department of Cancer Epidemiology and Genetics Masaryk Memorial Cancer Institute Brno Czech Republic
Department of Chronic Disease Epidemiology Yale School of Public Health New Haven CT USA
Department of Epidemiology and Biostatistics Memorial Sloan Kettering Cancer Center New York NY USA
Department of Epidemiology and Environmental Health University at Buffalo Buffalo NY USA
Department of Epidemiology Harvard T H Chan School of Public Health Boston MA USA
Department of Epidemiology Johns Hopkins Bloomberg School of Public Health Baltimore MD USA
Department of Epidemiology University of Hawaii Cancer Center Honolulu HI USA
Department of Epidemiology University of Texas MD Anderson Cancer Center Houston TX USA
Department of Health Sciences Research Mayo Clinic College of Medicine Rochester MN USA
Department of Medical Oncology Dana Farber Cancer Institute Boston MA USA
Department of Medicine Memorial Sloan Kettering Cancer Center New York NY USA
Department of Obstetrics and Gynecology New York University School of Medicine New York NY USA
Department of Population Science American Cancer Society Atlanta GA USA
Division of Aging Brigham and Women's Hospital Boston MA USA
Division of Cancer Epidemiology and Genetics National Cancer Institute Rockville MD USA
Division of Public Health Sciences Fred Hutchinson Cancer Research Center Seattle WA USA
Division of Research Kaiser Permanente Northern California Oakland CA USA
Faculty of Health Sciences University of Olomouc Olomouc Czech Republic
Genetic and Molecular Epidemiology Group Spanish National Cancer Research Centre Madrid Spain
Genomic Epidemiology Group German Cancer Research Center Heidelberg Germany
Hospital del Mar Institute of Medical Research Universitat Autònoma de Barcelona Barcelona Spain
IdiSNA Navarra Institute for Health Research Pamplona Spain
Information Management Services Silver Spring MD USA
Institute of Nutritional Science University of Potsdam Nuthetal Germany
International Agency for Research on Cancer Lyon France
Lunenfeld Tanenbaum Research Institute Sinai Health System Toronto Canada
Navarra Public Health Institute Pamplona Spain
Population Health Department QIMR Berghofer Medical Research Institute Brisbane Australia
Precision Medicine School of Clinical Sciences at Monash Health Monash University Clayton Australia
South Australian Health and Medical Research Institute Adelaide Australia
Specialized Institute of Hygiene and Epidemiology Banska Bystrica Slovakia
SWOG Statistical Center Fred Hutchinson Cancer Research Center Seattle WA USA
Yale Cancer Center and Smilow Cancer Hospital New Haven CT USA
Citace poskytuje Crossref.org
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