PMID- 34258619
OWN - NLM
STAT- MEDLINE
DCOM- 20211025
LR  - 20240324
IS  - 1938-3207 (Electronic)
IS  - 0002-9165 (Print)
IS  - 0002-9165 (Linking)
VI  - 114
IP  - 4
DP  - 2021 Oct 4
TI  - Hepcidin-regulating iron metabolism genes and pancreatic ductal adenocarcinoma: a 
      pathway analysis of genome-wide association studies.
PG  - 1408-1417
LID - 10.1093/ajcn/nqab217 [doi]
AB  - 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.
CI  - Published by Oxford University Press on behalf of the American Society for 
      Nutrition 2021.
FAU - Julian-Serrano, Sachelly
AU  - Julian-Serrano S
AUID- ORCID: 0000-0002-8912-8232
AD  - Division of Cancer Epidemiology and Genetics, National Cancer Institute, 
      Rockville, MD, USA.
FAU - Yuan, Fangcheng
AU  - Yuan F
AD  - Division of Cancer Epidemiology and Genetics, National Cancer Institute, 
      Rockville, MD, USA.
FAU - Wheeler, William
AU  - Wheeler W
AD  - Information Management Services, Silver Spring, MD, USA.
FAU - Benyamin, Beben
AU  - Benyamin B
AD  - Australian Centre for Precision Health, Allied Health and Human Performance, 
      University of South Australia, Adelaide, Australia.
AD  - South Australian Health and Medical Research Institute, Adelaide, Australia.
FAU - Machiela, Mitchell J
AU  - Machiela MJ
AD  - Division of Cancer Epidemiology and Genetics, National Cancer Institute, 
      Rockville, MD, USA.
FAU - Arslan, Alan A
AU  - Arslan AA
AD  - Department of Obstetrics and Gynecology, New York University School of Medicine, 
      New York, NY, USA.
FAU - Beane-Freeman, Laura E
AU  - Beane-Freeman LE
AD  - Division of Cancer Epidemiology and Genetics, National Cancer Institute, 
      Rockville, MD, USA.
FAU - Bracci, Paige M
AU  - Bracci PM
AD  - Department of Epidemiology and Biostatistics, University of California, San 
      Francisco, San Francisco, CA, USA.
FAU - Duell, Eric J
AU  - Duell EJ
AD  - Unit of Biomarkers and Susceptibility, Oncology Data Analytics Program, Catalan 
      Institute of Oncology, L'Hospitalet de Llobregat, Barcelona, Spain.
AD  - Colorectal Cancer Group, ONCOBELL Program, Bellvitge Biomedical Research 
      Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
AD  - Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), 
      Madrid, Spain.
FAU - Du, Mengmeng
AU  - Du M
AD  - Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer 
      Center, New York, NY, USA.
FAU - Gallinger, Steven
AU  - Gallinger S
AD  - Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada.
FAU - Giles, Graham G
AU  - Giles GG
AUID- ORCID: 0000-0003-4946-9099
AD  - Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Australia.
AD  - Centre for Epidemiology and Biostatistics, Melbourne School of Population and 
      Global Health, The University of Melbourne, Melbourne, Australia.
AD  - Precision Medicine, School of Clinical Sciences at Monash Health, Monash 
      University, Clayton, Australia.
FAU - Goodman, Phyllis J
AU  - Goodman PJ
AD  - SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, 
      USA.
FAU - Kooperberg, Charles
AU  - Kooperberg C
AD  - Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 
      Seattle, WA, USA.
FAU - Marchand, Loic Le
AU  - Marchand LL
AD  - Department of Epidemiology, University of Hawaii Cancer Center, Honolulu, HI, 
      USA.
FAU - Neale, Rachel E
AU  - Neale RE
AUID- ORCID: 0000-0001-7162-0854
AD  - Population Health Department, QIMR Berghofer Medical Research Institute, 
      Brisbane, Australia.
FAU - Shu, Xiao-Ou
AU  - Shu XO
AD  - Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, 
      Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, 
      Nashville, TN, USA.
FAU - Van Den Eeden, Stephen K
AU  - Van Den Eeden SK
AUID- ORCID: 0000-0002-5599-8387
AD  - Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
FAU - Visvanathan, Kala
AU  - Visvanathan K
AUID- ORCID: 0000-0002-0582-8005
AD  - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 
      Baltimore, MD, USA.
FAU - Zheng, Wei
AU  - Zheng W
AD  - Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, 
      Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, 
      Nashville, TN, USA.
FAU - Albanes, Demetrius
AU  - Albanes D
AUID- ORCID: 0000-0001-8330-4293
AD  - Division of Cancer Epidemiology and Genetics, National Cancer Institute, 
      Rockville, MD, USA.
FAU - Andreotti, Gabriella
AU  - Andreotti G
AD  - Division of Cancer Epidemiology and Genetics, National Cancer Institute, 
      Rockville, MD, USA.
FAU - Ardanaz, Eva
AU  - Ardanaz E
AD  - Navarra Public Health Institute, Pamplona, Spain.
AD  - IdiSNA, Navarra Institute for Health Research, Pamplona, Spain.
AD  - CIBER Epidemiologia y Salud Publica (CIBERESP), Barcelona, Spain.
FAU - Babic, Ana
AU  - Babic A
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
FAU - Berndt, Sonja I
AU  - Berndt SI
AD  - Division of Cancer Epidemiology and Genetics, National Cancer Institute, 
      Rockville, MD, USA.
FAU - Brais, Lauren K
AU  - Brais LK
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
FAU - Brennan, Paul
AU  - Brennan P
AD  - International Agency for Research on Cancer (IARC), Lyon, France.
FAU - Bueno-de-Mesquita, Bas
AU  - Bueno-de-Mesquita B
AUID- ORCID: 0000-0002-1834-1829
AD  - Department for Determinants of Chronic Diseases, National Institute for Public 
      Health and the Environment (RIVM), Bilthoven, The Netherlands.
FAU - Buring, Julie E
AU  - Buring JE
AD  - Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical 
      School, Boston, MA, USA.
FAU - Chanock, Stephen J
AU  - Chanock SJ
AD  - Division of Cancer Epidemiology and Genetics, National Cancer Institute, 
      Rockville, MD, USA.
FAU - Childs, Erica J
AU  - Childs EJ
AD  - Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns 
      Hopkins, Baltimore, MD, USA.
FAU - Chung, Charles C
AU  - Chung CC
AD  - Division of Cancer Epidemiology and Genetics, National Cancer Institute, 
      Rockville, MD, USA.
FAU - Fabianova, Eleonora
AU  - Fabianova E
AD  - Specialized Institute of Hygiene and Epidemiology, Banska Bystrica, Slovakia.
FAU - Foretova, Lenka
AU  - Foretova L
AD  - Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer 
      Institute, Brno, Czech Republic.
FAU - Fuchs, Charles S
AU  - Fuchs CS
AUID- ORCID: 0000-0003-1582-9842
AD  - Yale Cancer Center and Smilow Cancer Hospital, New Haven, CT, USA.
FAU - Gaziano, J Michael
AU  - Gaziano JM
AD  - Division of Aging, Brigham and Women's Hospital, Boston, MA, USA.
FAU - Gentiluomo, Manuel
AU  - Gentiluomo M
AD  - Department of Biology, University of Pisa, Italy.
AD  - Genomic Epidemiology Group, German Cancer Research Center, (DKFZ), Heidelberg, 
      Germany.
FAU - Giovannucci, Edward L
AU  - Giovannucci EL
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
FAU - Goggins, Michael G
AU  - Goggins MG
AD  - Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns 
      Hopkins School of Medicine, Baltimore, MD, USA.
FAU - Hackert, Thilo
AU  - Hackert T
AUID- ORCID: 0000-0002-7012-1196
AD  - Department of General, Visceral and Transplantation Surgery, Heidelberg 
      University Hospital, Heidelberg, Germany.
FAU - Hartge, Patricia
AU  - Hartge P
AD  - Division of Cancer Epidemiology and Genetics, National Cancer Institute, 
      Rockville, MD, USA.
FAU - Hassan, Manal M
AU  - Hassan MM
AD  - Department of Epidemiology, University of Texas MD Anderson Cancer Center, 
      Houston, TX, USA.
FAU - Holcatova, Ivana
AU  - Holcatova I
AD  - Institute of Public Health and Preventive Medicine, Second Faculty of Medicine, 
      Charles University, Prague, Czech Republic.
FAU - Holly, Elizabeth A
AU  - Holly EA
AD  - Department of Epidemiology and Biostatistics, University of California, San 
      Francisco, San Francisco, CA, USA.
FAU - Hung, Rayjean I
AU  - Hung RI
AD  - Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada.
FAU - Janout, Vladimir
AU  - Janout V
AD  - Faculty of Health Sciences, University of Olomouc, Olomouc, Czech Republic.
FAU - Kurtz, Robert C
AU  - Kurtz RC
AD  - Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 
      USA.
FAU - Lee, I-Min
AU  - Lee IM
AD  - Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical 
      School, Boston, MA, USA.
AD  - Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, 
      MA, USA.
FAU - Malats, Nuria
AU  - Malats N
AD  - Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre 
      (CNIO), Madrid, Spain.
FAU - McKean, David
AU  - McKean D
AD  - Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns 
      Hopkins, Baltimore, MD, USA.
FAU - Milne, Roger L
AU  - Milne RL
AD  - Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Australia.
AD  - Centre for Epidemiology and Biostatistics, Melbourne School of Population and 
      Global Health, The University of Melbourne, Melbourne, Australia.
AD  - Precision Medicine, School of Clinical Sciences at Monash Health, Monash 
      University, Clayton, Australia.
FAU - Newton, Christina C
AU  - Newton CC
AD  - Department of Population Science, American Cancer Society, Atlanta, GA, USA.
FAU - Oberg, Ann L
AU  - Oberg AL
AUID- ORCID: 0000-0003-2539-9807
AD  - Department of Health Sciences Research, Mayo Clinic College of Medicine, 
      Rochester, MN, USA.
FAU - Perdomo, Sandra
AU  - Perdomo S
AD  - International Agency for Research on Cancer (IARC), Lyon, France.
FAU - Peters, Ulrike
AU  - Peters U
AD  - Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 
      Seattle, WA, USA.
FAU - Porta, Miquel
AU  - Porta M
AUID- ORCID: 0000-0003-1684-7428
AD  - Hospital del Mar Institute of Medical Research (IMIM), Universitat Autonoma de 
      Barcelona, Barcelona, Spain.
FAU - Rothman, Nathaniel
AU  - Rothman N
AD  - Division of Cancer Epidemiology and Genetics, National Cancer Institute, 
      Rockville, MD, USA.
FAU - Schulze, Matthias B
AU  - Schulze MB
AD  - Department of Molecular Epidemiology, German Institute of Human Nutrition 
      Potsdam-Rehbruecke, Nuthetal, Germany.
AD  - Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany.
FAU - Sesso, Howard D
AU  - Sesso HD
AD  - Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical 
      School, Boston, MA, USA.
FAU - Silverman, Debra T
AU  - Silverman DT
AD  - Division of Cancer Epidemiology and Genetics, National Cancer Institute, 
      Rockville, MD, USA.
FAU - Thompson, Ian M
AU  - Thompson IM
AD  - CHRISTUS Santa Rosa Hospital-Medical Center, San Antonio, TX, USA.
FAU - Wactawski-Wende, Jean
AU  - Wactawski-Wende J
AUID- ORCID: 0000-0003-3096-9595
AD  - Department of Epidemiology and Environmental Health, University at Buffalo, 
      Buffalo, NY, USA.
FAU - Weiderpass, Elisabete
AU  - Weiderpass E
AUID- ORCID: 0000-0003-2237-0128
AD  - Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 
      Seattle, WA, USA.
FAU - Wenstzensen, Nicolas
AU  - Wenstzensen N
AUID- ORCID: 0000-0003-1251-0836
AD  - Division of Cancer Epidemiology and Genetics, National Cancer Institute, 
      Rockville, MD, USA.
FAU - White, Emily
AU  - White E
AD  - Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 
      Seattle, WA, USA.
FAU - Wilkens, Lynne R
AU  - Wilkens LR
AD  - Department of Epidemiology, University of Hawaii Cancer Center, Honolulu, HI, 
      USA.
FAU - Yu, Herbert
AU  - Yu H
AD  - Department of Epidemiology, University of Hawaii Cancer Center, Honolulu, HI, 
      USA.
FAU - Zeleniuch-Jacquotte, Anne
AU  - Zeleniuch-Jacquotte A
AD  - Department of Population Health and Perlmutter Cancer Center, New York University 
      School of Medicine, New York, NY, USA.
FAU - Zhong, Jun
AU  - Zhong J
AD  - Division of Cancer Epidemiology and Genetics, National Cancer Institute, 
      Rockville, MD, USA.
FAU - Kraft, Peter
AU  - Kraft P
AUID- ORCID: 0000-0002-4472-8103
AD  - Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, 
      MA, USA.
AD  - Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, 
      MA, USA.
FAU - Li, Dounghui
AU  - Li D
AUID- ORCID: 0000-0002-7542-0662
AD  - Department of Gastrointestinal Medical Oncology, The University of Texas MD 
      Anderson Cancer Center, Houston, TX, USA.
FAU - Campbell, Peter T
AU  - Campbell PT
AD  - Department of Population Science, American Cancer Society, Atlanta, GA, USA.
FAU - Petersen, Gloria M
AU  - Petersen GM
AD  - Department of Health Sciences Research, Mayo Clinic College of Medicine, 
      Rochester, MN, USA.
FAU - Wolpin, Brian M
AU  - Wolpin BM
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
FAU - Risch, Harvey A
AU  - Risch HA
AUID- ORCID: 0000-0001-5337-3941
AD  - Department of Chronic Disease Epidemiology, Yale School of Public Health, New 
      Haven, CT, USA.
FAU - Amundadottir, Laufey T
AU  - Amundadottir LT
AD  - Division of Cancer Epidemiology and Genetics, National Cancer Institute, 
      Rockville, MD, USA.
FAU - Klein, Alison P
AU  - Klein AP
AUID- ORCID: 0000-0003-2737-8399
AD  - Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns 
      Hopkins, Baltimore, MD, USA.
AD  - Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns 
      Hopkins School of Medicine, Baltimore, MD, USA.
FAU - Yu, Kai
AU  - Yu K
AD  - Division of Cancer Epidemiology and Genetics, National Cancer Institute, 
      Rockville, MD, USA.
FAU - Stolzenberg-Solomon, Rachael Z
AU  - Stolzenberg-Solomon RZ
AUID- ORCID: 0000-0003-3698-7006
AD  - Division of Cancer Epidemiology and Genetics, National Cancer Institute, 
      Rockville, MD, USA.
LA  - eng
GR  - U01 CA182883/CA/NCI NIH HHS/United States
GR  - P50 CA062924/CA/NCI NIH HHS/United States
GR  - R01 HL034595/HL/NHLBI NIH HHS/United States
GR  - P30 CA008748/CA/NCI NIH HHS/United States
GR  - HHSN268201600018C/HL/NHLBI NIH HHS/United States
GR  - UM1 CA182883/CA/NCI NIH HHS/United States
GR  - U01 CA247283/CA/NCI NIH HHS/United States
GR  - HHSN268201600001C/HL/NHLBI NIH HHS/United States
GR  - RO1CA154823/NH/NIH HHS/United States
GR  - HHSN268201600003C/HL/NHLBI NIH HHS/United States
GR  - R01 CA102765/CA/NCI NIH HHS/United States
GR  - U01 CA182934/CA/NCI NIH HHS/United States
GR  - UG1 CA189974/CA/NCI NIH HHS/United States
GR  - HHSN268201600002C/HL/NHLBI NIH HHS/United States
GR  - P50 CA102701/CA/NCI NIH HHS/United States
GR  - P30 CA015083/CA/NCI NIH HHS/United States
GR  - HHSN268201600004C/HL/NHLBI NIH HHS/United States
GR  - U01CA164973/BC/NCI NIH HHS/United States
GR  - R01 CA154823/CA/NCI NIH HHS/United States
GR  - R01 CA049449/CA/NCI NIH HHS/United States
GR  - U01 CA182913/CA/NCI NIH HHS/United States
GR  - 001/WHO_/World Health Organization/International
GR  - R01 CA098380/CA/NCI NIH HHS/United States
GR  - R03 CA123546/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Am J Clin Nutr
JT  - The American journal of clinical nutrition
JID - 0376027
RN  - 0 (Hepcidins)
RN  - E1UOL152H7 (Iron)
SB  - IM
MH  - Adenocarcinoma/*metabolism
MH  - Aged
MH  - Case-Control Studies
MH  - Female
MH  - Gene Expression Regulation, Neoplastic/*physiology
MH  - Genotype
MH  - Hepcidins/genetics/*metabolism
MH  - Humans
MH  - Iron/*metabolism
MH  - Linkage Disequilibrium
MH  - Male
MH  - Middle Aged
MH  - Pancreatic Neoplasms/*metabolism
MH  - Polymorphism, Single Nucleotide
PMC - PMC8488877
OTO - NOTNLM
OT  - epidemiology
OT  - genetic susceptibility
OT  - hepcidin
OT  - iron metabolism pathway
OT  - pancreatic cancer
EDAT- 2021/07/15 06:00
MHDA- 2021/10/26 06:00
PMCR- 2022/07/13
CRDT- 2021/07/14 07:14
PHST- 2021/01/14 00:00 [received]
PHST- 2021/06/08 00:00 [accepted]
PHST- 2021/07/15 06:00 [pubmed]
PHST- 2021/10/26 06:00 [medline]
PHST- 2021/07/14 07:14 [entrez]
PHST- 2022/07/13 00:00 [pmc-release]
AID - S0002-9165(22)00469-5 [pii]
AID - nqab217 [pii]
AID - 10.1093/ajcn/nqab217 [doi]
PST - ppublish
SO  - Am J Clin Nutr. 2021 Oct 4;114(4):1408-1417. doi: 10.1093/ajcn/nqab217.